Diabetes-Blogg

2009-07-27T10:09:00.000-07:00

People with diabetes urged to stay on popular insulin Lantus

By Julie Steenhuysen

CHICAGO (Reuters) - Dr. Louis Philipson has already started fielding calls from worried diabetics after new studies of 300,000 patients released on Friday suggested the Sanofi-Aventis insulin drug Lantus (insulin glargine) might raise the risk of cancer.

"I think the deluge is about to hit," Philipson, of the University of Chicago Medical Center, said in a telephone interview.

Diabetes experts are cautioning patients to keep taking Lantus, an artificial form of insulin called an insulin analog that is used by millions of people with type 1 and type 2 diabetes to control their blood sugar.

Four studies released in the journal Diabetologia raised concerns about the drug, but the results were conflicting.

"This not an emergency. This is just a question we have to answer now," said Dr. R. Paul Robertson, president of the American Diabetes Association and a diabetes researcher at the University of Washington in Seattle.

"The major thing is people should continue taking their insulin," Robertson said in a telephone interview.

Lantus is typically taken just once a day. It has been widely used since 2000.

Unlike human insulin, a hormone normally produced by the pancreas that helps the body use glucose for energy, Lantus has a slightly altered molecular structure that allows it to last longer in the body.

"It's frequently prescribed in the United States. When I have patients with type 1 or type 2 diabetes, I give that drug. It's been very effective," Robertson said.

All people with type 1 diabetes need to take insulin to survive; many patients with type 2 diabetes also need to take insulin to control their blood glucose.

Robertson said it is not clear if the same problems would be seen in Levemir, another long-acting insulin analog made by Denmark's Novo Nordisk.

"Lantus has been out there longer. Other drugs haven't had time to show they have the same kind of effects," he said.

The American Diabetes Association has recommended that patients continue on the treatment, and consult their doctor before making any changes.

Philipson said insulin is a type of compound called a growth factor and prior studies have shown that when insulin is added to cells in a cell culture, it makes them grow.

"That would also include tumor cells," he said.

Philipson said it may be that patients taking Lantus are simply exposed to insulin longer, and if they have any underlying tumors, the drug may accelerate tumor growth.

"Even though this information is early and the results are conflicting, it's still the case that using less of this drug is a good idea," he said.

He said patients with type 2 diabetes should use diet and exercise to improve their body's ability to use insulin, which may allow them to use less artificial insulin.

2009-07-27T10:07:00.000-07:00

REM sleep-related OSA linked with diabetes

By Megan Rauscher

NEW YORK (Reuters Health) - There is a statistically significant association between type 2 diabetes and obstructive sleep apnea (OSA) during REM sleep, results of a study indicate.

In comments to Reuters Health, principal investigator Dr. Kamran Mahmood said, "Type 2 diabetes is a multifactorial disorder. REM-related OSA and its metabolic effects need to be investigated in more depth, and this can provide another unique avenue for intervention and control of type 2 diabetes."

Mahmood from the University of Illinois in Chicago and colleagues evaluated a multi-ethnic sample of 1008 patients -- including Caucasians (16.9 percent), African Americans (66.9 percent) and Hispanics (14.9 percent) -- for OSA using polysomnography, an evaluation of brain waves and other body functions during sleep.

OSA occurs when the soft palate narrows during sleep closing off the airways causing breathing to stop for a few seconds or more. Normal breaths resume with a snort or choking sound and the sleeper temporarily wakes up. These continuous interruptions throughout the night cause drowsiness during the day. Among other effects, OSA increases the risk of heart disease.

Rapid eye movement (REM) sleep, one of the two major phases of sleep, is when dreaming occurs. As the name implies, it is characterized by rapid eye movement, but other than lung movements, no other body muscles move during this phase of sleep. It is thought to be necessary for memory consolidation.

The prevalence of type 2 diabetes was 30.1 percent in patients with OSA compared to 18.6 percent in patients without OSA, the investigators report in the June 15 issue of the Journal of Clinical Sleep Medicine.

According to the study team, patients with OSA - defined as an apnea-hypopnea index of 5 or more per hour (measurement of OSA severity) -- had a significantly increased unadjusted odds ratio for type 2 diabetes but this association became non-significant in analyses controlled for BMI, age, and other variables.

Middle-aged participants with OSA had 2.8-times higher odds for type 2 diabetes compared to younger or middle-aged participants without OSA, after controlling for variables.

Additionally, the adjusted odds ratio for type 2 diabetes was 2.0 in patients with REM sleep-related OSA, defined as a REM apnea-hypopnea index of 10 or more per hour, compared to patients without OSA.

"We believe that REM-related OSA is a marker of early OSA, especially in women and patients younger than 55 years," Mahmood noted in a prepared statement. "Generally, OSA is worse in REM sleep compared to non-REM sleep because of neurologically mediated impairment of skeletal muscles of upper airway and ventilation. This may be the reason for closer association of REM-related OSA and type 2 diabetes."

SOURCE: Journal of Clinical Sleep Medicine, June 15, 2009.

2009-07-27T10:06:00.001-07:00

High-fiber diets may reduce calcium in people with diabetes

By Will Boggs, MD

NEW YORK (Reuters Health) - High-fiber diets may slightly reduce calcium levels in patients with type 2 diabetes, according to a report in the June Diabetes Care.

High-fiber diets can help improve blood sugar levels and cholesterol levels in diabetics, but it is important that the diet is rich in soluble fiber as well as in calcium, said senior author Dr. Abhimanyu Garg in an email interview with Reuters Health. Otherwise, Garg added, patients may need to take calcium supplements.

In a study conducted at the clinical research center of the University of Texas Southwestern Medical Center at Dallas, Garg and colleagues compared the effects of a 6-week high-fiber diet and a 6-week moderate-fiber diet on mineral absorption and metabolism in 13 patients with type 2 diabetes.

Calcium levels in the urine and, to a lesser extent, the blood were significantly reduced in subjects given the high-fiber diet, the report indicates. Calcium absorption in the intestines was also slightly reduced.

Calcium levels in the blood are "very tightly regulated and even a slight decline on the high-fiber diet suggests that the impact of high fiber on calcium absorption is significant," Garg said.
"High-fiber diets offer many advantages to patients with diabetes and thus should be prescribed," Garg advised. "These include bowel regularity, reduction in LDL "bad" cholesterol, and improvement in (blood sugar) control. Instead of using processed fiber, patients should be advised to increase dietary fiber by consuming natural fruit, grains, and vegetables."

SOURCE: Diabetes Care, June 2009.

2009-07-27T10:02:00.000-07:00

Poorest at risk of worst diabetes

BBC Online Service

LONDON - The poorest people in the UK are more than twice as likely to have diabetes at any age than the average person, a charity has warned.

And those with the condition who live in the most deprived homes are also twice as likely to develop complications, Diabetes UK said.

Obesity, lack of exercise, poor diet and smoking are to blame, it added.

One public health expert said efforts to prevent and treat the disease should be targeted at the most vulnerable.

As of 2008, there were 2.5 million people diagnosed with diabetes in the UK.

Numbers have been climbing in recent years due to increased efforts to find people who were unaware they had the condition.

It has been predicted that by 2025, there will be more than four million people with diabetes in the UK.

The most common type is type 2 diabetes, which is generally associated with lifestyle factors, such as being overweight.

It is caused by the body not producing enough insulin or when the insulin that is produced does not work properly.

If not managed effectively it can lead to complications such as heart disease, stroke, kidney failure, blindness and amputation.

Deprivation

The report also found that women in England who live in homes with the lowest income are more than four times as likely to get diabetes as those who live in homes with the highest income.

And diabetes in Wales is almost twice as high in the most deprived areas compared to the least deprived.

Douglas Smallwood, Diabetes UK chief executive, said action is needed to prevent a generation of people living in deprivation "ending up in an early grave".

He said health authorities needed to raise awareness among those at high risk.

"In addition, the NHS must ensure that appropriate, high quality care is available across the country and that everyone, regardless of their socioeconomic status, is accessing it.

"Research has shown that people with diabetes in deprived or high ethnicity areas are less likely to have key health checks, putting them at increased risk of developing devastating complications such as heart disease, stroke, kidney failure, blindness and amputation.

"Finally, in these times of economic uncertainty when people are more likely to turn to cheaper, processed foods, food labelling must be clear and consistent to allow people to make informed choices about what they are eating."

Professor Alan Maryon-Davis, president of the UK Faculty of Public Health, said the figures were not surprising as the risk factors for diabetes were very closely associated with deprivation and hard to tackle.

"We do need to target efforts at the most vulnerable."

He added that the national vascular screening programme which started in April and is still gearing up would help diagnose people and help them manage the illness.

"But we need to set up a proper call and recall system, we can't just wait for people to go to the GP, it has to be done in a more active way."

Story from BBC NEWS:http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/8167519.stm
Published: 2009/07/26

2009-04-19T16:37:00.000-07:00

International Diabetes Federation moves offices

NEWS RELEASE

BRUSSELS, Belgium, April 20, 2009 - The International Diabetes Federation (IDF) today announced they have moved to new offices in Brussels. IDF is a federation of over 200 diabetes associations in over 160 countries and has its headquarters in Brussels, Belgium.

The Federation's work has expanded exponentially to meet the challenge of the growing global diabetes epidemic. Diabetes organizations around the world are applying for membership; the Executive Office in Brussels has expanded to support work in key areas of diabetes education, epidemiology and health economics. IDF also continues to build on the foundation of its advocacy, awareness campaigns - World Diabetes Day and Unite for Diabetes - and World Diabetes Congresses. The move to larger offices at Chaussee de La Hulpe 166, Brussels 1170 Belgium, will accommodate a growing staff and enable the Federation to host the global diabetes community in Federation headquarters. The move allows IDF to further its mission to promote diabetes care, prevention and a cure worldwide.

"The International Diabetes Federation is the global voice for diabetes" said Ann Keeling, CEO and Executive Director of the International Diabetes Federation. "In 2006 we secured a United Nations Resolution on diabetes; we are working tirelessly to put diabetes and Non-Communicable diseases at the heart of the global health agenda; and we're busy working to provide the evidence, the tools and the momentum to reverse the diabetes epidemic."

The Federation is the global advocate for the more than 250 million people with diabetes, their families and the many more at risk of developing diabetes. IDF is also the global source of information on diabetes prevalence, education and care. It works with a wide array of stakeholders including governments, civil society, health professionals, pharmaceutical and other industries, education and research institutions, employers and the wider community to raise diabetes awareness, encourage prevention efforts and to improve diabetes care. IDF is a non-governmental organization in official relations with the World Health Organization, the Pan-American Health Organization and associated to the United Nations' Department of Public Information.

According to IDF's Diabetes Atlas, by 2025, the number of people affected by diabetes is expected to balloon to 380 million. Diabetes has rapidly become one of the largest epidemics of the 21st century. The Federation is leading the battle and is working globally, regionally and locally to improve care, increase spending on diabetes prevention and care, provide education, provide and exchange data on diabetes and to raise awareness.

"One of our missions is to provide hope for people with diabetes. While diabetes is very serious, with proper education and care, diabetes is manageable and it is possible to live long and healthy life. Sadly, in many countries, essential diabetes medicines are unaffordable and diabetes becomes a death sentence, especially for children," said Keeling. "We created the blue circle as the global symbol for diabetes in 2006. It is a circle because that is a symbol of unity and it is blue because of the sky that unites us all. It is a happy coincidence that our new office is in the shape of a circle, a constant reminder of our symbol of unity and hope"

Ends
Note to Editors
Link to IDF logos - http://www.box.net/shared/eqpiz9sguv
New offices as of April 20, 2009:
International Diabetes Federation
Chaussee de La Hulpe 166
Brussels 1170
Belgium
Tel : +32-2-5385511
Fax : +32-2-5385114
Email : info@idf.org
Website : www.idf.org

2009-01-29T12:21:00.000-08:00

New York City Mayor Calls On U.S. Manufacturers To Reduce Salt Content Until It Results In A 50 Percent Cut In 10 Years

January 28, 2009

Marcia Kramer
CBS

NEW YORK ― Singer Jimmy Buffett will never find his "lost shaker of salt" in New York City or any other place in the country if Mayor Michael Bloomberg has his way. The mayor is waging a war on salt and he wants food manufacturers and restaurants to join his army … or else.

City officials said that people don't realize the salt content of the things they buy in the supermarket. For example, potato chips you would think are the saltiest thing in the store but they have only 180 milligrams per serving. Turkey meatballs, on the other hand, have 660 milligrams per serving. Marble cake has 300 per serving and chicken noodle soup has nearly 1,400 milligrams of salt per serving.

The city's plan is to get food manufacturers in the United States to agree to gradually start reducing salt content until it reaches a 50 percent cut in 10 years.

"Salt, when its high in the diet, increases the blood pressure and high blood pressure is a major factor for heart disease and stroke," said Dr. Sonia Angell of NYC's Cardiovascular Disease Prevention Program.

This is just Mayor Bloomberg's latest health initiative, following on the heels of a smoking ban, a ban on trans fats and forcing restaurants to post the calorie contents.

But many New Yorkers peppered the mayor with boos for his latest idea.

"I don't think it's that big a deal to look on the label, check the packaging and make the decision for yourself rather than have Bloomberg or whoever mandate what it is people should or shouldn't eat," said Paul Hope of Upper West Side.

"Nanny state. We don't need any more nanny state people can take care of themselves. We don't need the government to take care of us," said Patrick Keenan of Hell's Kitchen.

The city says it doesn't want to eliminate salt in food, just go back to the levels found during the 1970s.

Thomas Frieden, the city's health commissioner, said he wants manufacturers and restaurants to join the war on salt voluntarily. If they don't, the city could pass legislation making it the law.

2009-01-28T18:20:00.000-08:00

Blood-pressure drug alert issued

by ANDRÉ PICARD
From Saturday's Globe and Mail
January 17, 2009 at 2:00 AM EST

Taking two commonly prescribed blood-pressure drugs in combination can trigger severe heart and kidney problems, according to an alert issued Friday to patients and physicians.

The drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, are considered safe and effective on their own and when combined with other hypertension drugs, but ACE inhibitors and ARBs should not be used together, the Heart and Stroke Foundation is warning.

The group estimates that about 175,000 Canadians – most of them over the age of 65 – are taking this particular combination of drugs.

“This is a safety issue that the public and practitioners need to be aware of,” said Sheldon Tobe, a nephrologist at Sunnybrook Health Sciences Centre in Toronto. “Bringing blood pressure under control is very important, but with this particular combination the potential risks outweigh the benefits.”

Margaret Moy Lum-Kwong, director of high-blood-pressure strategy at the Heart and Stroke Foundation of Ontario, stressed that patients should not stop taking medications, even if they are taking ARBs and ACE inhibitors together, but discuss the matter with their physician.
“If you are on this particular combination treatment … go directly to your doctor for an alternative treatment,” she said.

High blood pressure, the leading risk factor for heart disease, is commonplace, affecting one in four men and one in five women.

A person is considered hypertensive with a blood-pressure reading of 140/90 millimetres of mercury (mmHg) or higher. Healthy adults should have a blood pressure in the range of 120/80 mmHg, although that target varies with age and other health conditions such as diabetes.

According to a study published last year, about 85 per cent of those with high blood pressure are aware of their condition and most are being treated successfully.

Blood pressure can often be controlled with lifestyle changes such as weight loss, healthy eating (particularly reducing salt consumption) and exercise, but many Canadians are treated with prescription drugs.

About two-thirds of hypertensive cases are treated with combinations of drugs, including diuretics, ACE inhibitors, ARBs and calcium channel blockers.

The safety and effectiveness of various combinations is being studied systematically. Last year, a landmark Canadian-led study showed that the combination of an ACE inhibitor and ARB was only marginally more effective at lowering blood pressure than either drug taken alone.

But it also revealed far more side effects among those taking the ACE-ARB combo, including fainting, diarrhea and dangerously elevated potassium levels that could result in kidney failure (and the need for dialysis) and even death.

Dr. Tobe stressed that severe complications were rare, but said there is no justification for putting patients at risk when there is no additional benefit.

“What we're doing here is refining therapy to make it safer,” he said.

Arthur Innes, a 57-year-old Torontonian who works in a long-term care facility, said he got his blood pressure checked as part of a physical for life insurance and was shocked to learn readings were dangerously high at 200/90 mm/Hg.

His family doctor prescribed a combination of ARB and ACE inhibitor. “These medications didn't make me feel very good. I was dizzy and had nausea all the time,” Mr. Innes said.

He was referred to a specialist and prescribed different medication; he now has his blood pressure under control and suffers no side effects.

“Taking the meds is important for your heart,” Mr. Innes said, “but you don't want medications that impair your way of life.”

[Eds note: these two types of medications are often used as part of the diabetes-cocktail]

2009-01-16T09:11:00.000-08:00

Common blood pressure drugs should not be combined

Friday, January 16, 2009

CBC News

Thousands of Canadians with high blood pressure are taking a combination of drugs that increases their risk of sudden cardiac death, kidney disease and other complications, the Heart and Stroke Foundation warned Friday.

Under new Canadian guidelines, patients taking a combination of ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) should not stop taking the medications on their own, but should see their family doctor as soon as possible to discuss whether to change treatment.

Angiotensin Converting Enzyme or ACE inhibitors such as Ramipril are a type of blood pressure medication that helps widens blood vessels, making it easier for blood to flow through.

Angiotensin II Receptor Blockers (ARBs) block the action of a peptide called angiotensin, which causes blood vessels to narrow, helping to relax the blood vessels and lower blood pressure.

Combination stresses kidneys

"There is a synergy that happens when you use this particular drug combination but, unfortunately, it is not a synergy that benefits patients," said Toronto nephrologist Dr. Sheldon Tobe, a spokesperson for the Heart and Stroke Foundation and an executive member of the committee that drafted the new guidelines.

"When you put the two drugs together, you don't get any additional protection against heart attacks and strokes and you get more negative side-effects," he added.

The drug combination is a major source of stress on the kidneys, with a trend towards requiring dialysis, said Margaret Moy Lum-Kwong, a spokersperson for the Heart and Stroke Foundation of Ontario who leads the group's high blood pressure strategy.

"The good news is that for patients who are on this particular combination treatment, that once you stop the combination, the risk is eliminated," Lum-Kwong said.

She added that people should know what medications they are on and why.

As many as 175,000 Canadians with high blood pressure may be currently treated with this combination of medications.

Most people with hypertension need to take two or more drugs and adopt a healthier lifestyle, the committee said.

But a Canadian-led trial published in the New England Journal of Medicine in April 2008 found the drug combination was only marginally better at lowering blood pressure than either drug alone, and patients taking both experienced more side-effects such as kidney problems.

The trial included 25,620 people who were age 55 or older with vascular disease or high-risk diabetes.

In updating the guidelines, the committee also considered other studies to understand the scope of the potential problem, Lum-Kwong said.

High blood pressure affects one in five Canadians, according to the foundation.

2009-01-07T12:01:00.000-08:00

Diabetics at risk of mental deterioration: U of A study

Thought function slowdown begins in early onset of disease, researchers find

by Keith Gerein
The Edmonton Journal

January 6, 2009

EDMONTON - In another red flag for health authorities trying to stem a growing diabetes epidemic, new University of Alberta research suggests adults who develop the condition can expect a slowdown in certain types of mental abilities.

This deterioration, which can affect activities such as driving and playing games, appears to occur near the onset of the disease and persists into old age, says the study published in this month's edition of Neuropsychology.

The results mean the rising number of adult diabetics around the world -- already known to be at greater risk for heart disease, hypertension and stroke -- may also be saddled with mild but lasting impairment to their thought functions.

"The basic idea of the study was to find what aspects of cognition were affected most and earliest," said lead author Roger Dixon, a U of A psychology professor.

For the study, Dixon's team analyzed several types of mental processes in 41 people between the ages of 53 and 90 with Type 2 adult-onset diabetes. Another 424 adults in good health were also tested for comparison.

The results reinforced previous findings that diabetes weakens cognition, but went further by identifying the abilities most affected.

Of the five "domains" tested, the diabetics performed significantly worse than the healthy adults in two areas -- processing speed and executive function.

Executive function is responsible for planning, abstract thinking, and working out unlearned approaches to novel situations.

In particular, Dixon said his team detected an impact on inhibition, which might make sufferers less able to stop themselves from saying something they know to be incorrect or inappropriate.

There were no major differences between the diabetic and healthy groups in tests of episodic and semantic memory, verbal fluency, and reaction time and perceptual speed.

This means the cognitive slowdown has little repercussion for most aspects of a diabetic's everyday life, but can become noticeable during activities that require a high degree of monitoring and response, Dixon said.

The study also found that among the diabetics, the pattern of mental deterioration was essentially the same across all age groups tested -- indicating the slowdown begins early on in the disease, the researchers suggest.

Dixon said scientists are still unsure exactly how diabetes causes cognitive degradation. His team's research was pulled out of a long-term project known as the Victoria Longitudinal Study, in which subjects are tracked at three-year intervals to examine the effects of aging.

Further research may determine whether the early mental decline from diabetes can get worse over time or add to normal, age-related impairment.

Dixon said early diagnosis and proper management, including a regimen of mental exercises, may help control the problem.

New cases of diabetes have nearly doubled over the past 10 years and are accelerating, according to the U.S. Centers for Disease Control. About 90 per cent of these cases in the United States are Type 2.

In Canada, the diagnosis rate is about 12 per cent for adults over 60.

2008-12-26T14:51:00.000-08:00

U.S. FDA warns Coca-Cola over nutritional claims on diet drink

Provided by: The Canadian Press
Written by: Matthew Perrone, THE ASSOCIATED PRESS
Dec. 23, 2008

WASHINGTON - Federal health regulators have scolded Coca-Cola for placing inappropriate nutritional claims on its Diet Coke Plus soft drink.

The Food and Drug Administration issued a warning letter to the company, objecting to the product's labelling, which describes the drink as "Diet Coke with Vitamins and Minerals."

Regulators said the beverage does not have enough nutrients to justify the use of the word "plus" in its name. According to the agency, foods labelled "plus" must have at least 10 per cent more nutrients than comparable products. Additionally, the FDA said it is inappropriate to add extra nutrients to "snack foods such as carbonated beverages."

In the Dec. 10 letter, the FDA calls on Coca-Cola to revise the drink's labelling and inform the agency of its plans within 15 days of receiving the message. The FDA posted the letter online Tuesday.

Coca-Cola said it will respond to the FDA in early January, but currently has no plans to change the label.

"This does not involve any health or safety issues, and we believe the label on Diet Coke Plus complies with FDA's policies and regulations," said spokesman Scott Williamson.

The company launched Diet Coke Plus in March 2007, touting it as a calorie-free soft drink with extra vitamins and minerals. According to the company's Web site, the drink contains vitamin B, zinc and magnesium.

Once a niche market, nutrient-enriched beverages have grown into multibillion dollar business, which includes everything from calcium-enhanced orange juice to energy drinks containing ginseng, ginkgo and other herbs.

In recent years the FDA has begun cracking down on companies that overstate the benefits of the products.

The FDA has endorsed health claims on several foods, but only after government researchers verified that the products help prevent disease. Oatmeal products, for example, can carry the FDA-approved claim, "may reduce risk of heart disease."

The FDA regularly issues warning letters to companies that do not follow regulations for manufacturing and marketing. The letters are not legally binding, but the agency can take companies to court if they are ignored.

Shares of Coca-Cola Co. fell 24 cents to $44.42 in midday trading Tuesday.

2008-12-26T14:44:00.000-08:00

Low- and No-Calorie Sweeteners

An EatingWell Guide for Diabetes
Provided by EatingWell.com

The debates in the nutrition world about the value of low- and no-calorie sweeteners are often loud and raucous, but when the discussion turns to their role in diabetes, the conversations become much more harmonious. Let's face it, the availability of something that makes food taste sweet, without contributing carbohydrate grams, can sometimes make life with diabetes a little easier. That said, there are still some important issues to keep in mind.

Safety
Currently, the U.S. Food and Drug Administration (FDA) has approved four low- or no-calorie sweeteners as safe for use: aspartame (NutraSweet, Equal), acesulfame potassium (Sunett, Sweet One), saccharin (Sweet'n Low, SugarTwin and other brands) and sucralose (Splenda). To earn FDA approval, these sweeteners had to undergo rigorous testing and be shown safe when consumed by the general public—including people with diabetes. However, some organizations—notably, the nonprofit consumer-advocacy group Center for Science in the Public Interest (CSPI)—remain skeptical. Of the currently approved sweeteners, only sucralose earns CSPI's vote as safe.

Taste
Low-calorie sweeteners have no problem in the sweetness department; most are hundreds of times sweeter than regular sugar. But some people find they have an aftertaste, or that the foods prepared with them "just don't taste right." It's a matter of personal preference, of course; some people claim saccharin has a bitter aftertaste, for example, while others appreciate that it isn't tooth-achingly sweet. And low-calorie sweeteners tend to be an acquired taste; people who regularly use a particular sweetener sometimes become loyal to its flavor profile. In our own Test Kitchen, we found sucralose, which is derived from cane sugar, came closest to the taste of regular sugar, but still had its own aftertaste.

Performance
If you use a low-calorie sweetener just to perk up your iced tea, just about any one will do. But when you want to use it for something more complex, like a batch of muffins, performance can be a problem. Aspartame, for instance, breaks down when heated, so it's a no-go in baking. Other problems result from the one-dimensionality of low-calorie sweeteners compared to sugar: while they contribute only sweetness, sugar adds volume and texture, and, when heated, it caramelizes, adding complex toasty flavors as well as an appealing browned look. Recreating those properties without using sugar can be tricky.

Substituting with Splenda
In the EatingWell Test Kitchen, sucralose is the only alternative sweetener we test with when we feel the option is appropriate. For nonbaking recipes, we use Splenda Granular (boxed, not in a packet). For baking, we use Splenda Sugar Blend for Baking, a mix of sugar and sucralose. It can be substituted in recipes (1/2 cup of the blend for each 1 cup of sugar) to reduce sugar calories by half while maintaining some of the baking properties of sugar. If you make a similar blend with half sugar and half Splenda Granular, substitute this homemade mixture cup for cup.
When choosing any low- or no-calorie sweetener, be sure to check the label to make sure it is suitable for your intended use.

What About Stevia?
While stevia (stevioside), a natural sweetener extracted from the leaves of the stevia plant, has not been approved by the FDA for use as a sweetener, it's widely available as a "dietary supplement" that makes no sweetening claims on its labels. Stevia is about 300 times sweeter than sugar, with a slight licorice flavor; some health-food aficionados seek it out as a "natural" alternative to manmade sweeteners.

The FDA hasn't given stevia the green light because of questions about its safety. There's a reason for setting the bar high: while the herb has been used safely for centuries in Paraguay, and since the 1970s in Japan, it's likely to be used much more liberally in the soft-drink-and-sweet-treat-loving United States. If you choose to use stevia, use it the way the Japanese and Paraguayans do, only in small amounts—say, to sweeten your coffee.

What About Fructose?
Fructose (sometimes called "levulose" on food labels) is a simple sugar that occurs naturally in foods, including fruits and honey; it's also a key component in table sugar (which is sucrose, a blend of half fructose and half glucose). While it has the same amount of calories and carbohydrate as sugar, fructose produces a lower and slower rise in blood glucose, and requires less insulin for the body to process. For that reason, some "health" or so-called "diabetic" foods are sweetened with fructose, and pure fructose is sold in the alternative sweetener section in supermarkets.

Should you buy fructose-sweetened foods? Most experts don't feel it's necessary or desirable. For one, foods sweetened with added fructose may contain other carbohydrates that can also affect your blood-glucose levels. And they cost more than traditionally sweetened foods. But perhaps the most important concern is that fructose can raise triglycerides and LDL cholesterol, potentially raising heart-disease risks. Some scientists and nutrition researchers are concerned about the rapidly growing presence of fructose in the food supply, largely through the increasing use of high-fructose corn syrup (HFCS).

HFCS, made by processing cornstarch to a highly sweet syrup, is cheaper than sugar, so it has been steadily replacing sugar in many foods and beverages, including soda, juice drinks, baked goods, breakfast cereals, desserts and condiments (ketchup, for example). Unlike fructose, HFCS is similar in composition to table sugar (about half glucose), so it doesn't have fructose's gentler effects on blood glucose. And because of its prevalence, it has become much easier to consume a lot of added fructose. Some experts believe the wide use of HFCS has played a part in the dramatic increases in the national obesity rate—which began its climb in the 1980s, when HFCS entered the food supply. Since people with type 2 diabetes are often overweight and at increased risk of heart problems, it makes sense to keep an eye on fructose by reading labels—and steering away from HFCS-sweetened foods. The American Diabetes Association recommends people with diabetes avoid fructose, other than that naturally occurring in foods.

What About Sugar Alcohols?
While their names sound less than appetizing, and sometimes like a boozy dessert sauce, sweetening agents like sorbitol, mannitol, xylitol, maltitol, lactitol and hydrogenated starch hydrolysates (HSH) are familiar to many people with diabetes. These so-called sugar alcohols are often added to food products such as "sugar-free" candy or gum, cookies or certain medications. They are listed on food labels under the Total Carbohydrate heading. Because these sweeteners are only partially digested compared to other sugars, they cause a lower rise in blood glucose. They also don't cause tooth decay. But their lack of digestibility can be a problem, causing stomach upset, gas or diarrhea in some people, especially if eaten in large amounts. The most important fact about sugar alcohols is that they still contribute some carbohydrate (about half is digested). To calculate how much, note the grams of carbohydrate contributed by any sugar alcohol listed on the food label, then subtract half that number from the Total Carbohydrate count.

2008-11-04T17:39:00.000-08:00

November is National Diabetes Awareness Month

Launch of JDRF Video Contest for kids with type 1 diabetes

TORONTO, Nov. 4 /CNW/ - Juvenile Diabetes Research Foundation (JDRF), the world's leading charitable funder of type 1 (juvenile) diabetes research, is celebrating National Diabetes Awareness Month this November with a variety of exciting awareness initiatives. The launch of the premiere JDRF Video Contest gives those living with type 1 diabetes the chance to create and star in a video featuring their personal trials and triumphs that impact many aspects of
their daily routine. United Nations-recognized World Diabetes Day on November 14 will be a highlight of the month with grassroots activities across Canada. Through November's initiatives, JDRF emphasizes the importance of research to find a cure for type 1 diabetes, a non-preventable disease affecting over 200,000 Canadians and their families.

"It is important for all Canadians to take some time this November to think about family, friends and colleagues who are impacted by diabetes, directly or indirectly," said Andrew McKee, JDRF President and CEO. "Most people do not understand what it means to live with type 1 diabetes, so the video contest we are launching will give Canadians the opportunity to share their story and personal struggle."

With the inaugural JDRF Video Contest, kids 13 and older with type 1 diabetes are invited to submit a creative three minute video with the theme "My T1 24/7 Story." A celebrity judging panel, including actor Colin Mochrie, TV-show host Carlos Bustamente, and mountain-climber Sébastien Sasseville, will choose the top three videos from among the entrants. They will be posted on www.jdrf.ca and the general public will vote for the winner.

In Spring 2009 the winner will be flown to Toronto to present his or her video at JDRF's annual general meeting in June. The approximate retail value of the "overnight trip" to Toronto prize (assuming a Vancouver departure) is $2,500. The contest closes at midnight (Eastern) on December 31, 2008. No purchase necessary. For more contest details, see the Official Rules at http://www.jdrf.ca/.

"Having diabetes is hard because I'm different from my friends in ways they don't know. When I get dressed I have to think about where to put my insulin pump, and before I eat I have to check my sugars and count carbohydrates. I hope my video will help my friends and family know what's like for me, and why it's so important to find a cure," said Krissy Keyworth of Vancouver, age 13, who is planning to enter the contest.

The Leafs Fund for Kids is also participating in National Diabetes Awareness Month by partnering with JDRF for the Maple Leafs Fund Charity of Choice Night on November 17th. JDRF Youth Ambassadors will interact with Leafs fans and appear on Leafs TV before the game. Maple Leafs mascot, Carleton, will wear a JDRF blue ribbon to show support for type 1 (juvenile) diabetes research.

For further information please visit http://www.jdrf.ca/, and the World Diabetes Day Canada website at http://www.worlddiabetes.ca/.

Type 1 Diabetes Facts

Over 200,000 Canadians have been diagnosed with type 1 diabetes.
Type 1 diabetes usually strikes in childhood or adolescence, and is often diagnosed before the age of 30.

To stay alive, people with type 1 diabetes must take multiple insulin injections daily or continually infuse insulin through a pump and test their blood sugar. While trying to balance insulin doses with their food intake and daily activities, children with this form of diabetes must try to avoid high blood sugars, which lead to a range of devastating complications, including heart disease, blindness and kidney disease, while also avoiding low blood sugars, which can be life-threatening. Although life-sustaining, insulin is not a cure nor does it prevent the debilitating
complications associated with the disease which can include kidney failure, blindness, nerve damage, amputation, heart attack and stroke.

Canada has sixth highest incidence rate of type 1 diabetes in children 14 years or younger in the world with the occurrence rate rising by three to five per cent per year; the greatest rise occurs in - five to nine year olds. The Federal government estimates that diabetes and its complications cost the Canadian economy more than $13.2 billion a year in health-care, absenteeism and lost productivity. The disease is a leading cause of adult blindness and end-stage kidney failure, and is the reason for most amputations, after accidents. In contrast to type 2 diabetes, in which the pancreas continues to produce insulin, type 1 diabetes is not preventable.

Type 1 Diabetes Symptoms

During November, JDRF is urging people to educate themselves about the symptoms of diabetes, which is critical because the disease can be mistaken or more common illnesses, such as the flu. But untreated, even over a very short timeframe, type 1 diabetes is life-threatening. The symptoms of type 1 diabetes, which often occur suddenly, are:
<< - Extreme thirst - Sudden weight loss
- Frequent Urination - Drowsiness, lethargy
- Sudden vision changes - Heavy, labored breathing
- Fruity, sweet or wine-like odor on breath - Stupor, unconsciousness
- Increased appetite >>

If you or your child exhibit one or more of these symptoms, you should call a doctor immediately. More information on type 1 diabetes and research leading to a cure is available at http://www.jdrf.ca/.

About JDRF

Juvenile Diabetes Research Foundation (JDRF) is the leading charitable
funder and advocate of type 1 diabetes research worldwide. Our mission is to
find a cure for diabetes and its complications through the support of
research. JDRF has been fundamentally involved in the support and delivery of
diabetes research advances. Our resilience, passion and progress in research
towards a cure, as well as advancements in science and management tools has
improved the lives of children and adults living with this complex disease.
The Foundation is structured on a business-world model that efficiently and
strategically directs resources to research aimed at finding a cure as soon as
possible. For more information please visit www.jdrf.ca

For further information:
Media contact:
Lesley Ciciretto,
National Communications Specialist,
Juvenile Diabetes Research Foundation,
W: (905) 944-4624, lciciretto@jdrf.ca

2008-11-04T17:37:00.000-08:00

Watching too much TV can boost diabetes risk

Tuesday, November 4, 2008
McClatchy Newspapers

No time for breakfast and too much TV time can trigger diabetes. Fitness magazine has identified nine surprising diabetes risk factors. The disease affects 21 million people in the U.S.
Skipping breakfast increases our risk as much as 50 percent, and watching TV for two or more hours per day boosts it 14 percent, according to Fitness.

Pam O'Brien, the magazine's article director, says the main reason for the story was to point out that people can lower their risk in about a month.

As a former no-breakfast type, Ms. O'Brien began forcing herself to eat breakfast a few years ago and has felt much better since.

"So many of us skip breakfast because we're busy and just grab a cup of coffee," she says. "It's one of the worst things you can do. People that eat high-fiber cereals respond better to insulin."

Diabetes, according to the American Diabetes Association, is caused when the body doesn't produce or properly use insulin. Insulin converts starches and sugars into fuel for the body.
While the exact cause is still unknown, the ADA points to studies that have concluded genetics and lifestyle factors such as obesity and lack of exercise appear to be linked to the disease.
Ms. O'Brien says her staff based its conclusions and risk factor percentages on university research and other studies and then crunched all the numbers.

While Fitness magazine targets women, the nine risks also affect men.

Ms. O'Brien's strategy to tackle the nine risk factors is to begin addressing two or three and gradually work in more.

"You don't want to feel like you have to change your life all at once," she says.

Also Online
Quiz: How much do you know about diabetic food choices?
Diabetes facts and symptoms 10 ways to be a smart diabetic
Diabetes glossary
Diabetes resources

2008-11-04T17:34:00.000-08:00

Use of Kids' Meds on the Increase
Obesity and its complications driving the trend, researchers say

by Steven Reinberg
HealthDay News
MONDAY, Nov. 3

Medication use among children across the United States is dramatically increasing as more kids are being treated for diabetes, asthma and attention-deficit hyperactivity disorder (ADHD), researchers report.

Increased prescribing may be due in large part to increasing obesity among children and the health consequences of that trend, researchers say.
"Across all the medication classes we looked at, the rates of use incre
ased -- sometimes dramatically," said study co-author Dr. Donna Halloran, an assistant professor of pediatrics at St. Louis University. "This is particularly concerning, given that several of these diagnoses have been linked to obesity -- diabetes, hypertension, depression, asthma."

The report was published in the November issue of Pediatrics.

For the study, Halloran's team looked at medication use among U.S. children from 2002 to 2005. Using a database of prescription claims from children with private health insurance, they were able to find prescriptions for almost 4 million children.

The researchers found that over four years, prescriptions for children aged 5 to 19 increased significantly. Among two drugs to treat type 2 diabetes, the use doubled. This increase was due to a 166 percent increase in prevalence of the disease among girls aged 10 to 14, and a 135 percent increase in prevalence among girls age 15 to 19.

In addition, the use of drugs to treat asthma rose by 46.5 percent, and the use of drugs to treat ADHD grew by 40.4 percent. The number of prescriptions for cholesterol-lowering drugs rose by 15 percent, the researchers found.

Halloran's group also found more modest increases in the use of blood pressure drugs and antidepressants (1.8 percent).

The increased rate of prescribing was much higher for girls than boys. For example, the use of drugs to treat type 2 diabetes increased 147 percent among girls, but only 39 percent among boys.

The use of drugs to treat ADHD increased 63 percent among girls and 33 percent among boys, and the use of antidepressants rose 7 percent among girls compared with 4 percent among boys.
"Whether the increased use of medications is a good thing really depends on your perspective," said study co-author Emily R. Cox, manager of outcomes research at Express Scripts Inc., in St. Louis. "Most people who would look at these numbers would indicate that these are worrisome trends."

"We need to understand what is driving this increase," Cox said. "Really, these are symptoms of underlying problems."

As the number of obese children increases, the number of children with chronic diseases is also increasing, Cox said. "That they are being treated is a good thing," she said. "The concern is, are doctors more likely to use drug therapy over diet and exercise?"

Dr. Michael Artman, head of the department of pediatrics at the University of Iowa, is concerned that children with chronic health problems who have private health insurance are getting better care than similar children who rely on government programs or who have no health insurance.
"I can imagine that the need is as great or even greater among disadvantaged children," Artman said. "We know the prevalence of those chronic conditions in disadvantaged socioeconomic classes is greater. This is kind of the tip of the iceberg in children's prescribing."

Artman also noted there is more data on prescribing medications to children, which makes doctors more confident in prescribing and means that children are getting better care.
"Now we actually have data on drug effects and side effects and toxicity and efficacy in children that we didn't have two or three decades ago," he said. "This is an important advance in pediatric medicine."

More information

For more about obesity in children, visit the U.S. National Library of Medicine.

SOURCES:
Emily R. Cox, Ph.D., manager, outcomes research, Express Scripts Inc., St. Louis; Donna Halloran, M.D., assistant professor, pediatrics, St. Louis University;
Michael Artman, M.D., professor and head, department of pediatrics, University of Iowa, Iowa City;
November 2008 Pediatrics

2008-11-04T17:33:00.000-08:00

U.S. diabetes rates double over the past decade

2008-11-04 14:01:38
Caymanmama.com - Health News News

Diabetes rate doubles over 10 years, US government review says

Bethesda, Maryland — The American diabetes epidemic is at a ten-year high, according to the government’s first state-by-state review of new diagnoses.

On Thursday, the review was released showing that the U.S. rate of new diabetes cases has doubled in the past decade, with the highest levels in the South.

Diabetes cases were most abundant in West Virginia, where approximately 13 in 1,000 adults were diagnosed with the disease. Minnesota saw the lowest rates with 5 in 1,000.

Nearly all of the cases were Type 2 diabetes, the type which is mostly linked to weight issues and obesity. The findings clearly reflect the stereotype that the souther U.S. states are the least active and are the heaviest linking them to more cases of heart disease.

“It isn’t surprising the problem is heaviest in the South — no pun intended,” said Matt Petersen, who oversees data and statistics for the American Diabetes Association.

Petersen indicated that thegovernment has pulled this information so as to have a better plan of action and to help health insurers locate the best places to enforce focus prevention campaigns.
The trend is increasing and the statistics are saddening. More than 23 million Americans have diabetes and that number is hastily increasing with nearly 1.6 million new cases diagnosed in adults over the age of 20 last year, according to the Centers for Disease Control and Prevention.
The report shows that West Virginia, South Carolina, Alabama, Georgia, Texas and Tennessee had the highest rates while Minnesota, Hawaii and Wyoming had the lowest.

2008-11-04T17:30:00.000-08:00

PhD student unlocks diabetes insulin mystery

By Tamara McLean
Australia Herald-Sun
November 05, 2008 11:58am

AUSTRALIAN scientists have uncovered a key clue in the mystery of how insulin works, bringing them closer to a cure for diabetes.

A Sydney PhD student Freddy Yip has solved a problem plaguing researchers worldwide for more than half a century - how insulin prompts fat and muscle cells to absorb glucose.

This process is defective in the growing number of people with type 2 diabetes so understanding it opens the way for new therapies to correct it.

"While we're certainly not saying we've found a way to cure diabetes, we are saying we've found a pretty significant clue," said David James, head of the diabetes program at the Garvan Institute for Medical Research.

"Since the 1920s, when Banting and Best discovered insulin, scientists have been battling to discover how it actually works," Professor James said.

"Then along comes Freddy Yip, doing his PhD, who unveils a completely novel action of insulin, one which we believe plays a fundamental role in glucose uptake."

The findings, published in the journal Cell Metabolism, focus on two intersecting problematic processes affecting diabetics, insufficient production of insulin in the pancreas after a meal and so-called insulin resistance, and the faulty uptake and storage of glucose in fat and muscle cells.
"In the cell we have series of motor proteins that have the ability to move other molecules from one place to another along intracellular railroad tracks," Mr Yip said.

"I have discovered that insulin activates a specific kind of motor protein known as Myo1c, which in turn performs a critical role in glucose uptake."

The motor protein helps move glucose transporter proteins from inside the cell to the surface membrane so that they can pump glucose into the cell.

The findings offer up a new target for diabetes treatment.

"We think there may be blockages in the signal between insulin and myo1c in people who develop insulin resistance," he said.

"If we're correct, it should be possible to target that pathway for development of new therapies."
Statistics show about 700,000 Australians suffered diabetes in 2005, a figure which has doubled since 1981.

2008-08-07T08:33:00.000-07:00

Another First for Diabetes:
Ontario becomes one of the world leaders in type 1 diabetes management

July 22, 2008

TORONTO - The Canadian Diabetes Association applauds the Government of Ontario for announcing the expansion of the provincial children’s insulin pump and supplies program to adult Ontarians with type 1 diabetes as part of the $741 million investment over 4 years in a new diabetes strategy.

Extending the free insulin pumps and supplies program to all Ontarians with type 1 diabetes removes a significant financial barrier to managing this condition and it will also help people who require an insulin pump prevent or delay the onset of heart attacks, strokes or kidney failure,” said Karen Philp, Acting Vice President, Research, Professional Education and Government Affairs, Canadian Diabetes Association. “We applaud the Government of Ontario for being one of the world leaders in the management of type 1 diabetes with this comprehensive strategy.”

Ontario is the first province in Canada—and is one of the first jurisdictions in the world–to provide this level of coverage for prescribed insulin pumps and supplies. Prior to today’s announcement, the Ontario insulin pump and supplies program was only available to children 18 years of age and under.

Insulin pumps are designed to deliver life-sustaining insulin at a steady rate based on an individual’s needs. A pump costs about $6,000 and an additional $3,600 a year for the insulin and associated supplies. Approximately 10 percent of the estimated 900,000 Ontarians living with diabetes today have type 1 diabetes.

Details of the Ontario Diabetes Strategy also announced today by the Ontario Minister of Health include plans to raise awareness of the prevention of type 2 diabetes through increased educational campaigns and the creation of a Diabetes Registry as a first step in implementing Ontario’s e-Health Strategy.

“The government’s Diabetes Strategy will support all Ontarians living with diabetes by giving them the skills, tools and information they need to better manage their condition and by being full partners in their own health,” added Philp. “The Diabetes Registry will also allow the government to set provincial targets for improving health outcomes and allow us to evaluate what’s working well and where. This will ultimately improve the health of Ontarians living with diabetes.”

The Canadian Diabetes Association works in communities across the country to promote the health of Canadians and eliminate diabetes through our strong nationwide network of volunteers, employees, healthcare professionals, researchers, partners and supporters. In the struggle against this global epidemic, our expertise is recognized around the world. The Canadian Diabetes Association: setting the world standard.

To learn more, visit diabetes.ca or call 1-800-BANTING (226-8464).

For information about insulin pumps for adults, see the following resources:
Assistive Devices Program
Questions and Answers : Insulin Pump Therapy
Ministry of Health and Long-Term Care

For media inquiries, please contact:
Randi Garcha
Marketing & Communications,
Ontario Canadian Diabetes Association
416-408-7207

2008-08-07T08:29:00.000-07:00

BMI and Mortality Inversely Linked in CHF, Confirming the Obesity Paradox

Reuters Health Information
by Megan Rauscher
Aug 05

NEW YORK - Overweight and obese patients with chronic heart failure (CHF) are at lower risk for death than their normal-weight counterparts, according to results of a meta-analysis of studies that examined the effect of body mass index (BMI) on mortality.

"Our paper provides evidence that a normal BMI is likely not the ideal BMI for heart failure patients," Dr. Antigone Oreopoulos from the University of Alberta, Edmonton, Canada noted in comments to Reuters Health.

Dr. Oreopoulos and colleagues reviewed nine observational studies measuring BMI and mortality in CHF patients and pooled the data to estimate the risk of death in patients who are underweight, overweight or obese compared to patients with a normal BMI. The studies involved a total of 28,209 CHF patients and had a mean follow up of 2.7 years.

According to the report in the July issue of the American Heart Journal, patients who were overweight (BMI 25.0-29.9) or obese (BMI 30 or greater) had lower all-cause mortality (relative risks 0.84 and 0.67, respectively) and cardiovascular mortality (RR, 0.81 and 0.60, respectively), compared to study patients with normal BMI.

In a risk-adjusted sensitivity analysis, being overweight or obese "remained protective against mortality," the researchers report, with adjusted hazard ratios of 0.93 and 0.88, respectively.
"CHF patients who were normal/underweight had the highest mortality," Dr. Oreopoulos noted.
"It remains unknown, however, if higher body fat levels are actually the cause of better outcomes in patients with heart failure."

"We believe there is a need for prospective studies to confirm these findings and elucidate potential mechanisms" for the potentially protective effect of increased BMI in CHF, Dr. Oreopoulos and colleagues conclude.

"Our findings," they point out, "are consistent with evidence in other chronic disease populations," including survivors of myocardial infarction and chronic hemodialysis patients, demonstrating lower mortality with higher BMI levels.

Am Heart J 2008;156:13-22.

2008-08-07T08:27:00.000-07:00

Soft Drinks and Fruit Drinks Linked to Diabetes Risk in African American Women

News Author: Laurie Barclay, MD

July 30, 2008 — Regular intake of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk for type 2 diabetes in African American women, according to the results of a prospective follow-up study reported in the July 28 issue of the Archives of Internal Medicine.

"Type 2 diabetes mellitus is an increasingly serious health problem among African American women," write Julie R. Palmer, ScD, from Slone Epidemiology Center, Boston University in Massachusetts, and colleagues. "Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third; however, to our knowledge, no data are available on African Americans regarding this issue. Our objective was to examine the association between consumption of sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes mellitus in African American women."

Since 1995, this study has observed 59,000 African American women, who reported on food and beverage consumption in 1995 and 2001 and completed biennial follow-up questionnaires to determine new diagnoses of type 2 diabetes. The present analyses involved data from 43,960 women who were free from diabetes at baseline and who provided complete dietary and weight information. The primary endpoint was the incidence of type 2 diabetes mellitus.

During 338,884 person-years of follow-up, 2713 incident cases of type 2 diabetes mellitus were identified. Higher intake of both sugar-sweetened soft drinks and fruit drinks was associated with a higher incidence of type 2 diabetes mellitus. The incidence rate ratio for 2 or more soft drinks per day was 1.24 (95% confidence interval [CI], 1.06 - 1.45), after adjustment for dietary factors and other confounding variables. The comparable incidence rate ratio for fruit drinks was 1.31 (95% CI, 1.13 - 1.52).

Although the association of diabetes with soft drink intake was almost entirely mediated by body mass index, the association with fruit drink consumption was independent of body mass index.

"Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women," the study authors write. "While there has been increasing public awareness of the adverse health effects of soft drinks, little attention has been given to fruit drinks, which are often marketed as a healthier alternative to soft drinks."

Limitations of this study include beverage consumption data collected at baseline, creating possible misclassification of exposure, and incident cases of type 2 diabetes based on self-report.

"Consumption of fruit drinks conveyed as high an increase in risk as did consumption of soft drinks," the study authors conclude. "The public should be made aware that these drinks are not a healthy alternative to soft drinks with regard to risk of type 2 diabetes."

In an accompanying editorial, Mark N. Feinglos, MD, CM, and Susan E. Totten, RD, from Duke University Medical Center in Durham, North Carolina, note that the greatest increase in weight was seen in those women who drank the most soft drinks.

"The critical issue in the development of diabetes is total caloric intake and subsequent weight gain rather than individual macronutrient composition, [but] modification of specific macronutrients might make it easier to decrease total calories," Drs. Feinglos and Totten write. "Until we have more information, we have to assume that calories trump everything else, and that our number 1 goal for the reduction of new cases of type 2 DM [diabetes mellitus] should be to reduce the intake of high-energy, low-benefit foods, particularly in young members of the most vulnerable populations."

The National Cancer Institute and the National Institute of Diabetes and Digestive and Kidney Diseases supported this study. Dr. Palmer has obtained funding. Another study author has received industry support from McNeil Consumer Healthcare and Boehringer Ingelheim.

Drs. Feinglos and Totten have disclosed no financial relationships.

Arch Intern Med. 2008;168:1485-1486, 1487-1492.

2008-08-07T08:23:00.000-07:00

Metabolic Syndrome Linked With Resistance to Thrombolysis in Stroke Patients

Reuters Health
Aug 01

NEW YORK - Patients with metabolic syndrome are more likely to experience resistance to thrombolysis in middle cerebral artery (MCA) ischemic stroke, according to a report in the July 15th Neurology.

Metabolic syndrome has been shown to be an independent risk factor for ischemic stroke, the authors explain, but its potential impact on acute ischemic stroke prognosis has not been carefully evaluated.

For the present study, Dr. Juan F. Arenillas from Germans Trias i Pujol Universitary Hospital in Barcelona, Spain, and colleagues conducted such an evaluation, in patients with and without metabolic syndrome who underwent thrombolysis with tissue plasminogen activator for acute MCA ischemic stroke.

Although metabolic syndrome did not appear to influence initial stroke severity, clots were more often resistant to lysis in patients with metabolic syndrome (41%) than in those without (11%).

In addition, patients without metabolic syndrome were more likely to recanalize fully than were patients with metabolic syndrome (81% versus 43%, respectively). Furthermore, at 24 hours after tPA administration, 57% of patients with metabolic syndrome had failed to recanalize fully, the investigators say, compared with only 19% of patients without metabolic syndrome.

Metabolic syndrome was independently associated with poor clinical outcome and a larger infarct volume in patients with atherothrombotic stroke, according to the researchers.

"The metabolic syndrome may not be only associated with an increased risk for incident and recurrent ischemic stroke, as previously known, but also with a poor response to thrombolytic therapy in patients with acute ischemic stroke," the authors conclude.

Neurology 2008;71:190-195.

2008-08-07T08:20:00.000-07:00

Diabetic eye disease may predict heart failure

Reuters Health

NEW YORK - In people with diabetes, a common eye condition called retinopathy more than doubles their risk of developing heart failure, new research suggests.

Diabetic retinopathy is the most common cause of blindness among working-aged Americans. The disease, which affects roughly half of diabetics in the U.S., is caused by damage to the blood vessels in the back of the eye.

As reported in the Journal of the American College of Cardiology, Dr. Tien Y. Wong from the University of Melbourne in Australia and colleagues analyzed data from 1,021 adults with type 2 diabetes who were without heart or kidney disease when the study began. Nearly 13 percent of the subjects did, however, have diabetic retinopathy.

During 9 years of follow-up, 10.1 percent of the patients developed heart failure, the investigators note.

Overall, 21.6 percent of patients with retinopathy developed heart failure compared with just 8.5 percent of those without retinopathy. After accounting for other factors that may have influenced the association, diabetic retinopathy increased the risk of heart failure by 2.2-fold.

Editorialists Dr. Hector O. Ventura and Dr. Madhavi Reddy, from the Ochsner Clinic Foundation in New Orleans, comment that these findings could have important implications for clinicians.

"Current guidelines already identify the need for routine screening for retinopathy in the diabetic patient. In addition to appropriate vision care," they suggest that "the detection of retinopathy might now also warrant a fuller cardiac evaluation and closer follow-up to prevent the development of heart failure."

SOURCE: Journal of the American College of Cardiology, April 22, 2008.

2008-08-07T08:18:00.000-07:00

'Low glycemic' diet helpful in youth with diabetes

Reuters Health

NEW YORK - In children and adolescents with type 1, or insulin-dependent, diabetes, consumption of a low glycemic index diet may improve blood sugar control, according to results of a National Institutes of Health-sponsored study.

Glycemic index, or GI, refers to how rapidly a food causes blood sugar to rise. High-GI foods, like white bread and potatoes, tend to spur a quick surge in blood sugar, while low-GI foods, such as lentils, soybeans, yogurt and many high-fiber grains, create a more gradual increase in blood sugar.

Dr. Tonja R. Nansel of the National Institute of Child Health and Human Development and colleagues tested the effects of high GI and low GI meals on blood sugar levels using continuous blood sugar monitoring in 20 type 1 diabetics who were between the ages of 7 and 16 years.

The findings, reported in the journal Diabetes Care, suggest that a low GI diet can improve blood sugar control "to a clinically meaningful degree above that obtained by careful carbohydrate counting and contemporary insulin regimens," Nansel noted in comments to Reuters Health.

"When consuming the low GI diet, blood glucose (sugar) levels were in the target range 66 percent of the time compared to 47 percent of the time when consuming the high GI diet," she explained. "This difference was statistically significant."

When consuming the low GI diet, study subjects also demonstrated significantly lower daytime average blood sugar levels compared to the high GI diet and fewer blood sugar excursions.

"It is plausible" based on the results of this study, Nansel said, "that a low glycemic index diet may reduce the dose of insulin required while improving blood sugar control.

SOURCE: Diabetes Care April, 2008.

2008-08-07T08:15:00.000-07:00

Diabetic weight-loss plan yields long-term success

By Martha Kerr
Reuters Health

SAN FRANCISCO - Researchers at the Joslin Diabetes Center report that a 12-week weight-loss program they devised for patients with type 2 diabetes continues to have a positive, long-lasting effect on weight loss 1 year later, long after patients are off on their own.

The findings of a 1-year follow-up of the 12-week "Why WAIT" weight-loss program were presented here this week at the 68th Annual Scientific Sessions of the American Diabetes Association by principal investigator Dr. Osama Hamdy.

The study involved 85 patients with type 2 diabetes, average age 54 years and a disease duration of approximately 10 years. The average weight was 235 pounds, average body mass index (BMI) was 38.4, average hemoglobin A1C was 7.5 percent, and average waist circumference was 46.7 inches.

Patients completed the 12-week diet and exercise program and were followed for another year without structured intervention.

Twelve weeks of the intervention resulted in an average weight loss of 24.6 pounds -- more than a 10 percent reduction -- a waist circumference reduction of 3.6 inches, and an average drop of 0.9 percent in A1C to 6.6 percent, indicating good control of blood sugar.

After 1 year of follow-up, weight remained lower than before the patients began the diet by more than 18 pounds -- a long-term loss of 7.6 percent. However, A1C levels increased to approximately 7.4 percent.

Overall, 55 percent of participants continued to lose weight on their own, Hamdy said. The other 45 percent gained back approximately 5 pounds, but their final weight remained 2.0 percent lower than their pre-diet weight.

Blood pressure, both top and bottom readings, were significantly lower at 12 weeks and 1 year compared with pre-diet readings, he added. Cholesterol levels improved significantly at 12 weeks, but had returned to pre-diet levels at 1 year, except for HDL, the "good" cholesterol, which remained significantly higher.

Hamdy said there was evidence that kidney function improved as well, with a small decrease in protein in the urine.

"The clinical implications are enormous," Hamdy told Reuters Health. "We've been glucose-focused for a long time. We need to be weight-focused. We need to focus on the cause of the problem and not the result of the problem."

The mainstays of the "Why WAIT?" program are a low carb diet and tailored exercise. "We use significant calorie reduction and reduce carbohydrates to 40 percent of calories and increase protein to 30 to 40 percent of calories -- this is key for patients to maintain muscle," Hamdy said. "In addition, we teach patients how to exercise, especially the type and the amount, and make sure it is age-appropriate. This is very important."

He added, "The main reason that patients regain weight is that they decrease their protein intake and don't exercise as much. The weight they gain is mostly fat, and visceral fat."

There is also an economic benefit. "Weight reduction leads to a reduction in need for medications. We saw a 65 percent-reduction in medical costs, or about $560 per year per patient -- and patients feel better," Hamdy reported.

2008-08-07T08:12:00.000-07:00

US advisers urge higher bar for new diabetes drugs

By Lisa Richwine
Reuters Life!

SILVER SPRING, Md. - U.S. regulators should require drugmakers to study the potential heart risks of all new diabetes medicines, an advisory panel said.

The recommendation could force companies to run longer and more expensive studies and delay new entrants in a $6 billion U.S. market that was hit last year by concerns surrounding GlaxoSmithKline PLC's diabetes pill Avandia.

"Although it might be a little more burdensome... we need more studies," said Dr. Clifford Rosen, a panel member and endocrinologist at the Maine Center for Osteoporosis.

Now, companies generally need to show only that their medicines lower blood sugar levels. That approach is inadequate for patients, panel members said.

The group of outside experts that advises the Food and Drug Administration voted 14-2 to recommend companies do a long-term study of cardiovascular effects or provide equivalent evidence to rule out an "unacceptable" risk of heart problems.

Studies need to last as long as five years to detect heart attacks, strokes and other problems, several panel members said. Many endorsed the idea of starting the study before approval and completing it after a drug reaches the market.

The requirement should apply to all experimental drugs even if they show no signs of concern in early testing, the committee said.

"That's a shift in expectations of what we are asking for. It's a higher level... of assurance that you've excluded cardiovascular risks," said Dr. John Jenkins, director of the FDA's Office of New Drugs.

Some drugs already on the market also may need more study of cardiovascular safety, panel members said.

The FDA will decide what rules to impose on companies but usually follows panel recommendations.

Diabetes medicines are among the biggest selling drugs. U.S. sales of the leading medicines exceeded $6 billion in 2007, according to healthcare information company IMS Health.

Several drugmakers, including Glaxo, Bristol-Myers Squibb Co, AstraZeneca Plc, Eli Lilly and Co and Amylin Pharmaceutical Co, are working to bring new diabetes drugs to the market.

If the FDA sets strict requirements, "you're going to see increased research and development budgets, and you're probably also going to see less development in diabetes," said Morningstar analyst Damien Conover.

Higher standards could help Merck & Co Inc by delaying rivals to its fast-selling drug Januvia, Conover said.

Nearly 24 million Americans have diabetes, the U.S. government estimates. Most cases are type 2 diabetes, which experts link to obesity, poor diet and lack of exercise.

Diabetics produce less insulin, or their bodies use it less effectively, which makes blood sugar rise. That can damage blood vessels and organs, leading to blindness, kidney disease, limb loss and heart disease.

Experts agree blood-sugar control helps prevent complications such as damage to the eyes and kidneys. But no conclusive evidence exists that any diabetes drug reduces heart disease, the top killer of diabetics, FDA officials said.

Concern that diabetes medicines may damage the heart arose last year when a study by Cleveland Clinic researchers found Glaxo's Avandia increased the chances of a heart attack.

Glaxo has said Avandia's safety is comparable to similar pills. But the company agreed to add a strong warning that the drug might increase heart attack risk with a note that the data was inconclusive. Studies of cardiac effects are continuing.

2008-08-07T08:11:00.000-07:00

Testosterone gel benefits some men with diabetes

By Megan Rauscher
Reuters Health

NEW YORK - Men with type 2 diabetes or the metabolic syndrome, or both, are prone to have low testosterone levels. If so, testosterone replacement therapy with a gel applied to the skin may improve their response to insulin and their sexual function, according to the results of a new clinical trial.

Testosterone levels fall if testicular function is subnormal, a condition termed hypogonadism. "Consideration should be given to screening type 2 diabetic and metabolic syndrome patients for hypogonadism," Dr. T. Hugh Jones told the Endocrine Society's annual meeting in San Francisco this week.

Jones, of Barnsley Hospital and the University of Sheffield in the UK, and colleagues tested the effect of a testosterone gel (Tostran) on insulin resistance and symptoms of hypogonadism in 221 men with low testosterone levels.

One average, the men were 60 years age with a body mass index of 32, in the obese range. Eighty percent had metabolic syndrome, 64 percent had type 2 diabetes, and 44 percent had both. They were randomly allocated to use the testosterone gel daily or a matching placebo gel.

The study showed a statistically significant improvement in insulin sensitivity in testosterone-treated men at 6 and 12 months, Jones reported.

Testosterone therapy also led to a significant improvement in the score on a standard assessment of erectile function after 6 and 12 months.

Adverse events were similar in the two groups. Skin-related problems were the most commonly reported adverse events, experienced by 19 (17 percent) placebo-treated and 27 (25 percent) testosterone-treated men.

"These data tell us that replacement therapy for low testosterone in hypogonadal males not only improves sexual function but, more importantly, can also have an impact on insulin sensitivity," Jones said. "Long-term improvements in insulin resistance may help to improve cardiovascular and other diabetes complications and improve quality of life in this at-risk population."

"Awareness of the problems caused by low testosterone is becoming more widespread and its connection to health issues like diabetes continues to become increasingly apparent," he added.

"As the incidence of hypogonadism continues to grow along with the aging population, we need to ... implement a more rigorous screening program, particularly in men with type 2 diabetes."
The study was sponsored by ProStrakan, with US headquarters in Bedminster, New Jersey, makers of Tostran (also marketed as Fortigel, Tostrex and Itnogen).

2008-08-07T08:06:00.000-07:00

Broccoli may undo diabetes damage

Tuesday, 5 August 2008 00:12 UK
BBC News Online

Eating broccoli could reverse the damage caused by diabetes to heart blood vessels, research suggests.

A University of Warwick team believe the key is a compound found in the vegetable, called sulforaphane.

It encourages production of enzymes which protect the blood vessels, and a reduction in high levels of molecules which cause significant cell damage.

Brassica vegetables such as broccoli have previously been linked to a lower risk of heart attacks and strokes.

People with diabetes are up to five times more likely to develop cardiovascular diseases such as heart attacks and strokes; both are linked to damaged blood vessels.

The Warwick team, whose work is reported in the journal Diabetes, tested the effects of sulforaphane on blood vessel cells damaged by high glucose levels (hyperglycaemia), which are associated with diabetes.

They recorded a 73% reduction of molecules in the body called Reactive Oxygen Species (ROS).
Hyperglycaemia can cause levels of ROS to increase three-fold and such high levels can damage human cells.

The researchers also found that sulforaphane activated a protein in the body called nrf2, which protects cells and tissues from damage by activating protective antioxidant and detoxifying enzymes.

Countering vascular disease

Lead researcher Professor Paul Thornalley said: "Our study suggests that compounds such as sulforaphane from broccoli may help counter processes linked to the development of vascular disease in diabetes.

"In future, it will be important to test if eating a diet rich in brassica vegetables has health benefits for diabetic patients. We expect that it will."

Dr Iain Frame, director of research at the charity Diabetes UK, stressed that research carried out on cells in the lab was a long way from the real life situation.

However, he said: "It is encouraging to see that Professor Thornalley and his team have identified a potentially important substance that may protect and repair blood vessels from the damaging effects of diabetes.

"It also may help add some scientific weight to the argument that eating broccoli is good for you."

2008-06-16T10:03:00.000-07:00

Is There a Link Between Diabetes and Glaucoma?

Posted 04/22/2008
Rod Foroozan, MD

Although the most important identified risk factor for open-angle glaucoma (OAG) is elevated intraocular pressure, a number of other factors, including ethnicity and systemic conditions, may come into play.

Ethnicity has proved a potent risk factor, with blacks having a higher risk for OAG and developing more severe optic neuropathy than whites. More recently, research into the Hispanic-American population has shown a high rate of OAG (4.7%) among Latinos.[1]

Based in part on reduced ocular blood flow, researchers suspect that cardiovascular diseases, such as diabetes mellitus, may also play a role.

Prior population-based studies, however, have found variable results when assessing an association between diabetes and OAG.[2,3] Now, the authors of the large, population-based Los Angeles Latino Eye Study (LALES) have sought to determine whether there is an association between type 2 diabetes and OAG in Latinos.

Source: http://www.medscape.com/viewarticle/571412?src=mp&spon=22&uac=50127HN

2008-06-16T10:00:00.000-07:00

Workplace programmes can improve health - study

GENEVA (Reuters) - Workplace programmes targeting physical inactivity and unhealthy dietary habits are effective in mitigating the impact of obesity, diabetes and heart disease, according to a study published on Monday.

Deaths from non-communicable diseases such as heart disease, stroke, cancer and diabetes are forecast to rise 17 percent in 2005-2015, said the joint study by business thinktank the World Economic Forum and the U.N.'s World Health Organisation (WHO).

The impact of these deaths and health problems on the economies of different countries is dramatic, with China forecast to lose $557.7 billion in the period, Russia $303.2 billion and India $236.6 billion, it said.

"Enhancing employee productivity, improving corporate image and moderating medical care costs are some of the arguments that might foster senior management to initiate and invest in WHP (workplace health promotion) programmes," it said.

Unhealthy diets and excessive energy intake, physical inactivity and tobacco use are major risk factors for non-communicable diseases, it said.

In 2005 about 35 million people died of non-communicable diseases such as heart disease, stroke, cancer and diabetes, accounting for 60 percent of all deaths worldwide, it said.

This is projected to rise to 47 million deaths a year in the next 25 years, the study said.

Around 80 percent of these deaths occur in low and middle-income countries that also have to deal with infectious diseases, poor maternal and perinatal conditions and nutritional deficiencies, it said.

Successful workplace programmes are linked to business objectives, enjoy strong management support, involve staff from the start and are adapted to social norms, it said.

The study cited scientific evidence that healthy diet and adequate physical activity - at least 30 minutes of moderate activity at least five days a week - help prevent non-communicable disease.

The study, based on programmes in rich countries mainly in Europe and North America, said further research was needed, especially for poor countries.

The study was presented as the WHO's annual World Health Assembly opened in Geneva. Business leaders attending the launch urged the 193-member state forum to tackle the causes of chronic disease in the workplace.

(For the report click on: www.weforum.org/en/initiatives/Wellness/index.htm)

2008-06-16T09:58:00.000-07:00

Half of people with diabetes in U.S. have arthritis, CDC says

By Julie Steenhuysen

CHICAGO (Reuters Life!) - People with diabetes are twice as likely to have arthritis, putting them in a double bind as the pain in their joints keeps them from getting the exercise they need to keep both diseases at bay, the U.S. Centers for Disease Control and Prevention said on Thursday.

They found that more than half of U.S. adults diagnosed with diabetes also have arthritis. "The prevalence of arthritis in a diabetic population is astoundingly high," said Dr. John Klippel, president of the Arthritis Foundation in a telephone interview. "If in fact you have both conditions, you are quite unlikely to be physically active," he said.

According to the report, nearly 30 percent of diabetics with arthritis are likely to be physically inactive, compared with 21 percent of diabetics who do not have arthritis.

That compares with 17.3 percent of adults with arthritis alone who are inactive, and 10.9 percent of adults with neither condition who are inactive.

The CDC said the study suggests the pain of arthritis presents a barrier to physical activity - the very thing that might offer people some relief.

"For people with diabetes, physical activity helps control blood glucose and risk factors for complications. For people with arthritis, physical activity reduces pain and improves function," said Janet Collins, director of the CDC's National Center for Chronic Disease Prevention and Health Promotion.

Klippel thinks two things stand in the way.

"Because arthritis affects the joints and is associated with pain, people with arthritis, when they begin to exercise, experience more pain," he said. "The other thing is there is a common misconception that exercise is bad for arthritis and it will damage joints."

He said many forms of exercise are in fact "joint-safe," including walking, swimming and biking. "If people walked 30 minutes a day it would have a profound effect on reducing their pain and improving their symptoms," he said.

Given the scope of the problem, Klippel said the finding will likely affect the way doctors and policymakers go about encouraging their patients to exercise.

"Public health programs that are directed at controlling diabetes are going to need to pay a lot more attention to arthritis if they hope to get people to be physically active," he said.

The report is based on data gathered from a random telephone survey in 2005 and 2007.

People were asked if they had ever been diagnosed with arthritis or diabetes.

It does not say what type of arthritis people had -- osteoarthritis, rheumatoid arthritis or another form -- or if people had type 2 diabetes, the most common kind that is associated with obesity and lack of exercise. Type 1 diabetes is an autoimmune disease often diagnosed at an early age.

2008-06-16T09:56:00.000-07:00

Low-carb diets work for overweight people with diabetes

By Joene Hendry

NEW YORK (Reuters Health) - Overweight people with type 2 diabetes can keep their weight and blood sugar under control over the long term by following a low-carbohydrate diet, Swedish researchers report.

"It is indeed possible to have a lasting success in the treatment of some of these patients," Dr. Jorgen Vesti Nielsen told Reuters Health.

The participants in the study limited their carbohydrate intake to 20 percent of total calories. The most significant effect of this low-carb diet is the absence of hunger, Nielsen added.

The consequent reduction in food intake allows the body to use its own stores of fat for fuel, which results in weight reduction, explained Nielsen, from the Blekingesjukhuset diabetes clinic, in Karlshamn, Sweden.

Moreover, avoiding starch-rich bread, pasta, potatoes, rice, and breakfast cereals, and limiting carbohydrate intake to 80 to 90 grams a day primarily from vegetables, salad, and crisp bread, also minimizes the glucose spikes that make it necessary for people with diabetes to take insulin, Nielsen said.

Nielsen and colleagues had previously reported superior weight loss and glucose control over a 22-month period among 16 obese patients with diabetes who followed a low-carbohydrate diet compared with 15 similar patients following a diet containing 55 to 60 percent of energy from carbohydrates.

In their current study, in the BioMed Central journal Nutrition and Metabolism, Nielsen's group reports 44 months of follow up data.

"Of the 16 patients, five have retained or reduced bodyweight since the 22 month point and all but one have lower weight at 44 months than at start," the investigators report. Furthermore, glucose levels dropped soon after starting the diet and have stayed down over the 44 month period.

"Advice to obese patients with type 2 diabetes to follow a 20% carbohydrate diet with some caloric restriction has a lasting effect on bodyweight and glycemic control," the investigators conclude.

SOURCE: Nutrition and Metabolism, May 2008

2008-06-16T09:35:00.000-07:00

Test misses 2 out of 3 pre-diabetic kids: Canadian study

Monday, June 16, 2008
The Canadian Press

Obese children at risk of developing Type 2 diabetes may not be getting the news soon enough to take preventive action because the test used to gauge their condition is not sensitive enough, a new study suggests.

Researchers at McMaster University in Hamilton showed the standard test alone — called a fasting glucose test — missed two out of three children diagnosed as pre-diabetic by the fasting glucose test followed by a second test, a glucose stress test.

Under-diagnosing the problem means that kids and their families are missing an opportunity to make important lifestyle changes that have been shown to lower the risk of developing full-blown diabetes. Those changes are increasing exercise, losing weight and changing dietary habits.

"Really it is the recognition on both the part of the physician and to some extent on the part of the family that the child has experienced some negative metabolic effect from the obesity," lead author Dr. Katherine Morrison, a pediatric endocrinologist, said in an interview.

"Many parents don't think that kids can get health consequences. And so they don't think about them."

Morrison presented the findings Sunday to the annual meeting of the Endocrine Society in San Francisco.

She and her colleagues studied 172 obese children aged five to 17 who had joined a program to help them reach and maintain a healthy weight.

All children underwent evaluation for risk factors for diabetes or the precursor condition, pre-diabetes.

Fasting glucose test missed condition

When the children were tested using the fasting glucose test — which checks the blood for sugar levels after a fast — eight per cent were found to be pre-diabetic. But when the children went through the second test, the glucose stress test, 25 per cent met the criteria for pre-diabetes.

The American and Canadian diabetes associations recommend the fasting test only.

The stress test is a bit like cardiac stress tests, which check the heart's ability to cope with the rigours of exercise. In the glucose stress test, children who have fasted and been tested are then given a sugary liquid to drink and their blood sugar levels are again tested two hours later.

Morrison said the test shows whether the individual can process sugar normally or has impaired ability to metabolize it.

Until relatively recently, it was thought Type 2 diabetes was only a disease of later life — which is why it used to be called late onset diabetes. But it is now known that even adolescents can develop it. The condition contributes to heart disease, suggesting people who develop it early in life may face complications by mid-life.

In fact, Morrison said a longitudinal study that looked at cardiovascular risk factors in children who were then followed into adulthood found that those with multiple risk factors such as diabetes were at a vastly higher risk of having a heart attack by age 48 than other young adults.

"This tells us that the length of time that your body's exposed to these risk factors is also important in terms of developing heart disease down the road," she said.

"Clearly we have to become more aware of it. We've sort of always assumed this was an adult problem and we weren't going to think about it. But the research is telling us that perhaps we should be."

Funding for the study came from the Canadian Institutes for Health Research and from the Heart and Stroke Foundation of Canada.

2008-05-01T07:39:00.000-07:00

Australian scientists report weight loss breakthrough

Mon Apr 28, 7:00 PM

SYDNEY (AFP) - Australian scientists may have discovered how to help people lose weight without cutting back on food, a breakthrough that could pave the way for fat-burning drugs.
Researchers in Melbourne found that by manipulating fat cells in mice they were able to speed up the animals' metabolisms.

They found that when a particular enzyme, known as angiotensin converting enzyme (ACE), was removed, mice were able to eat the same amount as other mice but burn more calories and therefore gain less weight.

Animals without the enzyme were on average 20 percent lighter than normal mice and had 50 to 60 percent less body fat, senior researcher at the Howard Florey Institute Michael Mathai said.

"It is very clear that they do have less body fat," he told AFP.

Mathai, who is also a lecturer in nutrition at Victoria University, said the slimmer mice also appeared to have less chance of developing diabetes because they processed sugar faster than normal mice.

He said the research, to be published Tuesday in the US-based Proceedings of the National Academy of Sciences, could be used to develop drugs to assist weight loss.

Drugs which impair the action of ACE already exist and are mostly used to combat high blood pressure.

"The drugs are out there because they are used for hypertension," he said.

"So we know their safety and their tolerability. What we don't know is whether or not they will work in humans. And we don't know whether it will work in all obese humans."

Mathai said it could be a question of finding the right dosage of hypertension medication, or developing a new type of drug of the same class, to be used as weight-loss pills.

"This might be one way in which you can increase metabolic rate in combination with managing nutrition to limit the intake of calories," he said.

Mathai said the research, conducted at the Howard Florey Institute, Victoria University, La Trobe University, Deakin University, the Baker Institute and the University of Melbourne, was yet to pinpoint why the genetic manipulation led to weight loss.

"Because we deleted the gene, the gene is gone from the whole body, that means that it is gone from all tissues including the brain," he said.

"And so we don't know whether it's a direct effect of the deficiency in the tissue or whether it's something coming from the brain."

2008-04-14T12:52:00.000-07:00

Better Diabetes Foot Care Leads to Fewer Amputations

NEW YORK (Reuters Health) Mar 27 - Following an initiative to provide better diabetes foot care in the South Tees area of northeastern England, rates of diabetes-related lower extremity amputations fell substantially, according to the results of a study published in the March issue of Diabetes Care.

Dr. Ronan J. Canavan, of St. Columcille's Hospital, Dublin, Ireland, and colleagues identified all cases of lower extremity amputation (LEA) in the South Tees region from July 1, 1995, to June 30, 2000.

Of the 454 LEAs (66.3% in men) identified, 223 were related to diabetes (49.1%).

Among diabetic patients, LEA rates decreased from 564.3 per 100,000 persons with diabetes in the first year to 176.0/100,000 in the fifth year. Over the same time period, non-diabetes-related LEA rates increased from 12.3 to 22.8 per 100,000 persons without diabetes, the researchers found.

"These diverging trends mark a significant improvement in care for patients with diabetic foot disease as a result of better organized diabetes care," Dr. Canavan's team writes.

"Our study shows the importance of including a non-diabetes-related LEA comparison," they add. "A case-control study would be an efficient approach to further explore the specific changes seen in our study."

Diabetes Care 2008;31:459-463.

-->

2008-04-14T12:46:00.000-07:00

Intensive intervention benefits those with type 2 diabetes

NEW YORK (Reuters Health) - Among high-risk type 2 diabetics, an intensive intervention with multiple drug combinations and behavioral modification has sustained benefits, a Danish study shows.

The study involved 160 adults with type 2 diabetes and microalbuminuria - a complication of diabetes marked by small amounts of the protein albumin in urine. It is the first sign of kidney disease and a marker of increased risk of heart disease.

Participants were randomly assigned to usual care or to an intensified regimen of tight blood sugar control along with low-dose aspirin, cholesterol-lowering agents and blood pressure medication. They were treated for an average of 7.8 years and then followed for 5.5 years.

According to Dr. Oluf Pedersen from the University of Aarhus, and associates, after 13.3 years of follow-up, far fewer individuals in the intensive-therapy group than the usual care group had died (24 versus 40).

There were 51 cardiovascular events, including 9 deaths from cardiovascular causes, in 25 patients in the intervention group. By contrast, there were 158 cardiovascular events in the usual care arm, including 19 deaths, in 48 patients.

"The reductions in risk -- a 59% reduction in the relative risk and a 29% reduction in the absolute risk -- in the composite of cardiovascular events fit with projections from trials involving single risk factors," the investigators note in this week's issue of The New England Journal of Medicine.

Adults who originally received intensive management were significantly less likely to develop diabetic kidney disease, to experience progressive nerve damage, or to require dialysis or eye treatment, Pedersen and his associates report.

SOURCE: The New England Journal of Medicine, February 7, 2008.

2008-04-14T12:45:00.000-07:00

Just how low should blood sugar go?

By Julie Steenhuysen

CHICAGO (Reuters) - Conventional thinking among doctors who treat people with type 2 diabetes has been the lower the blood sugar levels, the better.

Many doctors are now taking a second look.

A massive study of diabetics with a high risk of heart disease known as ACCORD has found that lowering blood sugar levels to what is considered normal for healthy people proved deadly for some, researchers said on Wednesday.

Older patients who underwent intensive therapy to reach that level had higher rates of death than a group of patients in the same study who were treated more conservatively.

"The study was designed asking the question if you really control blood sugar, do you actually prevent death?" said Dr. Faramarz Ismail-Beigi of the University Hospitals Case Medical Center in Cleveland, Ohio, one of the study's researchers.

"I think in the intensive group, the answer is no. It doesn't prevent heart attacks and stroke," he said.

Patients in the intensive treatment group of the ACCORD study were aiming for a hemoglobin A1c level - a standard measure of blood sugar -- of 6 percent or below. They achieved an average of 6.4 percent, whereas the more conservative treatment group had A1c levels of about 7.5 percent.

"We can move millions of people into this zone with a certain amount of resources," Ismail-Beigi said. To move them all down to 6, you would need five to 10 times more resources. In terms of public health, it makes a huge difference."

Dr. James Dove, president of the American College of Cardiology, said the study was a bit unsettling.

"I think it offers some concern and caution," Dove said in a telephone interview. "The standard theory has been the lower the blood sugar the better off it was for the patient in decreasing the side effects of diabetes."

Researchers at the National Heart, Lung and Blood Institute, which funded and organized the ACCORD trial, said they will study why patients in the aggressive arm of the study fared worse.

2008-04-14T12:43:00.000-07:00

Test helps detect diabetic nerve trouble

NEW YORK (Reuters Health) - The indicator plaster neuropad, or IPN, is a new test that can help diabetic patients identify nerve damage brought on by diabetes, clinicians report in the journal Diabetes Care.

"The IPN can be performed by the patient at home in 10 minutes, and the result can be offered to the doctor in the next visit," Dr. Nicholas Tentolouris from Athens University Medical School in Greece told Reuters Health.

"The test offers the opportunity to the patients to participate actively in the prevention of the devastating complications related to diabetic foot problems," he added.

The IPN turns a pink color when nerve conduction is normal and a blue color when nerve damage is present.

In a study involving 156 diabetic patients and their health care providers, the in-home IPN test proved reliable and accurate for the diagnosis of diabetic nerve damage, also called peripheral neuropathy, which can cause numbness, pain, and tingling sensations in the feet.

Patients and health care providers agreed in 90.3 percent of the cases, deciding that the IPN results were normal or abnormal.

Patients consistently rated the IPN test instructions as easy to understand, easy to use, and easy to evaluate. About one fifth of the patients said they needed help performing the test.

"The results of the tests agree with those obtained by more complex tests used for the diagnosis of the diabetic neuropathy," Tentolouris said.

Currently there is no treatment for diabetic peripheral neuropathy, "and prevention of this complication with good metabolic control is the only available option," Tentolouris explained. "Therefore, patients with an abnormal IPN test -- that is patients with peripheral neuropathy -- will be educated for the care of their feet, they will be instructed to use proper footwear, and they will have their feet examined by the health care professionals more often."

Tentolouris and colleagues recommend that patients with diabetes use the IPN once per year for the detection of peripheral neuropathy.

SOURCE: Diabetes Care, February 2008.

2008-04-09T20:23:00.000-07:00

How Can We Unlock the Mystery of Patient Nonadherence?

From Medscape Med Students
Roundtable Discussion

Posted 04/01/2008
Graham A. Walker; Pennie Marchetti, MD

Graham Walker, Medical Student: We Need to Understand How Patients Really Live

How much of pathology ... isn't?

I just saw a patient come into the hospital who was taking metoprolol tartrate 100 mg 3 times a day. He was on a number of other high doses of antihypertensive medications (the typical metoprolol tartrate dose is twice daily.) All of his irregular regimens and dosing schedules pointed me toward the idea that this was a case of nonadherence, not resistant hypertension. (Okay, and the fact that this patient had been discharged from the anticoagulation clinic for nonadherence clued me in, too.)

They say that the most common cause of resistant or refractory hypertension is patient nonadherence, but how many other refractory problems have similar etiologies? Notice that I'm saying "nonadherence" instead of "noncompliance," as the former implies that the patient and physician have together worked out some sort of "treatment plan" -- although often it doesn't seem like the case.

Sometimes I wonder how many medical mysteries could be solved if we focused on the patient's social history, beyond just the "alcohol, tobacco, drugs" bit. Is the patient not taking his or her meds? And if so, why not?

Is it forgetfulness? Maybe they need a better reminder system.

Is it cost? Maybe we can try a generic drug.

Is it access? Maybe we can have the medication(s) sent to the patient's home.

Incorrect administration? Maybe we can educate the patient.

I'm reminded of a paramedic ride-along I did as part of an Emergency Medicine rotation. Going into people's homes -- seeing how they truly live day to day -- can instantly illuminate a patient's story. No wonder the patient didn't seek medical attention until he could barely breathe, he can't get down his 4 flights of stairs. No wonder the patient isn't taking her medications, she's feeding her 12 cats instead. How much are we missing by not seeing our patients "in the wild?"

Instead of doing more tests with risks, or giving more medications with side effects, maybe it would be more cost-effective (and patient-effective) to rule out the social aspects of the disease first. Patients may be reluctant to tell their doctor about any social barriers that might prevent them from following the doctor's orders, but if we can get patients to trust us and not feel judged, so that we can get the data we need to improve their health, we all win: lower costs, fewer unnecessary medications prescribed, and more diagnostic mysteries solved.

Pennie Marchetti, MD: Some Patients Need Firm Guidance

As Graham points out, it's the wise physician who takes into account his patient's social situation and cultural biases to plan a tolerable treatment that has at least half a chance of being implemented. But Graham's solutions, as sound and practical as they are, aren't likely to make much of a dent in the rate of overall compliance, or "adherence," if you prefer.

This is an issue that's been studied for years now, and the reasons patients give for not taking their medicines are much more complicated and run much deeper into their psyches than cost and access.[1] In one survey of nonadherent patients, 51% said they didn't take their medication because they didn't think it was necessary, and another 22% said they just didn't want to take it. In a survey of elderly patients, 21% said they didn't take their medication because they figured it wouldn't work, while another 22% thought it better to suffer the illness than risk side effects of medication. Only 10% cited cost as a barrier, and that was in the 1990s when there was no Medicare prescription drug benefit.

Prescribing generics, improving access, and designing memory aids are easy. What's hard is getting patients to take their illnesses as seriously as we do. And that's where I would argue that the issue isn't so much "adherence" as "compliance." Failure to "adhere" implies that the patient shares the desire to treat whatever ails him. If the surveys are accurate, that's clearly not the case most of the time. Instead, the root of the problem appears to be an inability of some patients to recognize that they are subject to the laws of nature. It is a failure to comply with reality.

This is a much more difficult problem to solve. It means that the doctor must not only establish a rapport and earn the patient's respect, but also persuade him to alter his basic beliefs and assumptions about both his body and medicine. Sometimes, just getting to the point of agreement on what the problem is can be an insurmountable barrier.

I once had a diabetic patient who was convinced that it was best for him to have a blood sugar in the 300-400 range. He was willing to take enough medicine and watch his diet to keep it there, but he stalwartly refused to bring it any lower. He even monitored his blood sugar daily to keep it in his own desired range. I never succeeded in getting him to lower his goal, even in small increments. He was a trucker, and he feared that 1 hypoglycemic episode would mean loss of his trucking license. He wasn't taking any chances. He had excellent insurance coverage, with many educational resources available to him -- including coverage of a diabetic nurse educator and an insurance-provided chronic disease management program -- but nothing persuaded him. Over the 12 years that he was my patient, I never made 1 inch of headway in dislodging his deeply held belief that a blood sugar of less than 300 was too close for comfort to hypoglycemia. Maybe his new doctor will do a better job.

This brings me to a discomfiting realization that has lately begun to creep into my consciousness: maybe some of our patients are noncompliant because we ourselves are too compliant. Like an overindulgent parent who can't understand why his/her children misbehave, perhaps we overindulge our patients by tolerating their lapses in judgment.

Last week, one of my more recalcitrant hypertensives came back from a visit to the cardiologist with a normal blood pressure for the first time in 3 years. The cardiologist didn't change any of his medications or alter any of the dosages. I asked my patient what it was that the cardiologist said to him that made him realize his hypertension was a problem. My patient revealed the secret: "He told me all the things you told me. He's just meaner and scarier than you are." Evidently, it's all in the delivery.

In my better moments, I know that the mean and scary approach isn't going to work with everyone. For every patient who is persuaded by it, there is surely another who is forever frightened away from professional medicine. But that's part of the art of medicine -- to find a treatment approach that works best with any given personality. Like all art, it is imperfect. We do A and hope that B will happen. In the end, perhaps all we can do is our best over and over again in the hope that it will be enough.

2008-04-09T20:19:00.000-07:00

Exercise, Insulin, and Type 2 Diabetes

From Medscape Diabetes & Endocrinology
Ask the Experts about Insulin Therapy in Type 2 Diabetes
Posted 03/31/2008

Teresa L. Pearson, MS, RN, CDE

Question: Is there a guide for reducing the insulin dose during exercise for people with type 2 diabetes who are on basal/bolus insulin therapy?

Response from Teresa L. Pearson, MS, RN, CDE
Director, Diabetes Care, Fairview Health Services, Minneapolis, Minnesota

Exercise is a key component of a healthy diabetes treatment regimen, but when insulin is involved -- even in a person with type 2 diabetes -- precautions should be taken. Before embarking on an exercise program, the American Diabetes Association (ADA) emphasizes that a person with type 2 diabetes should be evaluated for cardiovascular disease or other conditions that might contraindicate certain types of exercise. It is important that the exercise program be individualized on the basis of findings of the evaluation as well as the therapy regimen.

There are other variables that need to be considered: How often does the person currently exercise? If he or she is not very active, the likelihood of hypoglycemia is greater. The length of time the person is active and the level of intensity will affect blood glucose response as well. Other medications, such as sulfonylureas or pramlintide, need to be considered.

Basically, if the person is on a basal/bolus insulin regimen, the primary concern is the prevention of hypoglycemia. The ADA recommends checking blood glucose before, after, and then several hours after exercise because hypoglycemia can occur hours after exercise. For exercise that continues for 30 minutes or more, carbohydrate (CHO) intake or the rapid-acting or short-acting insulin may need to be adjusted. If the blood glucose level is less than 100 mg/dL, the person should take 15 g of CHO before starting the activity. If the person is planning to exercise for 1 hour or longer, blood glucose should be checked during exercise. If blood glucose is below 100 mg/dL, 15 g of CHO may need to be added.

If the exercise is planned, the rapid-acting (or short-acting) insulin dose should be reduced 30% to 50%. It is better to be conservative at first. The short- or rapid-acting insulin dose given within an hour following the exercise may need to be reduced. It is important to keep good records of all blood glucose values, the duration and intensity of the activity, and CHO intake, and to use the information to guide adjustments in the future. The response will be different for everyone on the basis of the level of insulin resistance and physical fitness.

If the exercise is not planned and it has been more than 2 hours since the last meal, it is recommended that the person take an additional 15-20 g of CHO within 15 minutes of initiating the exercise for every 30 minutes of exercise. Again, this is a conservative recommendation that should be adjusted on the basis of response. In overweight individuals, this approach should be used only for unplanned activity; the preferred approach would be to reduce the insulin in order to avoid additional caloric intake.

Gradually increasing exercise and keeping good records will help keep everything in balance. Remember, it is important to consider activities that patients may not think of as exercise, such as shoveling snow, mowing the lawn, or gardening. Additional recommendations that can help your patients reduce the incidence of hypoglycemia include:

Don't exercise when insulin is peaking;
Avoid injecting into the arms or legs; use the abdomen to ensure more even absorption of insulin;
If exercising late in the day, have a snack before bedtime to avoid a delayed hypoglycemic reaction during the night; and
Don't forget hydration; fluids should be replenished during exercise, especially when exercise lasts for more than 1 hour and there is significant perspiration.
All in all, the best rule of thumb is to be proactive and prevent problems before they occur.

Further Reading

Berger M. Adjustment of insulin and oral agent therapy. In: The Handbook of Exercise. Rudeman N, Devlin JT, Schneider SH, Kriska A, eds. Alexandria, Va: American Diabetes Association; 2002:365-376.

Mullooly CA. Physical activity. In: Mensing C, ed. The Art and Science of Diabetes Self-Management Education. American Association of Diabetes Educators; 2006:297-319.

Sigal RJ, Casteneda-Sceppa C, Kenny GP, White RD, Wasserman DH. Physical activity/exercise and type 2 diabetes: a consensus statement. Diabetes Care. 2006;29:1433-1438.

Steppel JH, Horton ES. Exercise. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders. American Diabetes Association; 2004:149-156.

This activity is supported by an independent educational grant from Novo Nordisk.

2008-04-09T20:16:00.000-07:00

Initial Therapy in an Obese, Symptomatic Patient With Type 2 Diabetes

From Medscape Diabetes & Endocrinology
"Ask the Experts about Insulin Therapy in Type 2 Diabetes"
Posted 03/31/2008

Jay Huber, DO

Question: Would you begin insulin therapy immediately in an obese, 50-year-old patient with recently diagnosed type 2 diabetes patient who is symptomatic (not ketoacidotic) with fasting blood glucose levels of 312 mg/dL and a glycated hemoglobin of 11.2%? There is no intercurrent disease.

Response from Jay Huber, DO
Assistant Program Director, University of North Dakota Center for Family Medicine, Bismarck, North Dakota

Early and aggressive control of hyperglycemia is an important concept. In a patient such as the one described in this question, it is unlikely that a single antidiabetic drug other than insulin will achieve glycemic control. It is also highly likely that insulin will be required at some point, because the disease progresses. At the time of the diagnosis of type 2 diabetes, less than 50% of pancreatic beta-cell function remains,[1] and loss of beta-cell mass and function will continue, making insulin necessary at some point.

The benefits of early and aggressive control of hyperglycemia have been demonstrated in multiple trials.[2-4] Recently, the Steno-2 trial[5] showed that intensive therapy led to significant reductions in vascular complications, as well as cardiovascular and all-cause mortality. Li and colleagues[6] showed significant improvement and long-lasting glycemic control with intensive use of insulin at the time of the diagnosis. Aggressive control and targeting glycated hemoglobin (A1C) levels to < 6.5% have been associated with reduction of all-cause mortality and cardiovascular events.[7]

As always, lifestyle interventions, diet, and weight control are paramount to the successful management of diabetes. Education and self-management are also of great importance, and must be initiated at the time of diagnosis. An effective option for the obese individual described in this question is a once-daily analog basal insulin. Close follow-up and titration to target are key. The PREDICTIVE 303 trial gives us an easy and safe model for titration of basal insulin.[8]

The use of metformin in conjunction with basal insulin is supported by the European Association for the Study of Diabetes guidelines, and if renal function is sufficient for the use of metformin, it would be my recommendation to start concomitant metformin as well.

This activity is supported by an independent educational grant from Novo Nordisk.

2008-04-09T20:14:00.000-07:00

Insulin Therapy and Weight Gain

Posted 03/31/2008

George Y. Chao, MD
Medscape Diabetes & Endocrinology

Question: Why do patients gain weight while on insulin therapy?

Response from George Y. Chao, MD
Medical Director, Diabetes Program, Memorial Hospital, Modesto, California;
Chief, Division of Endocrinology, Sutter Gould Medical Foundation, Modesto, California

It is well known that insulin treatment is associated with weight gain. Before the discovery of insulin, the treatment of type 1 diabetes mellitus was limited to a "starvation diet," and most patients became quite cachectic and emaciated before they died. When the first patients were treated with insulin, their glycemic control improved; their nutritional status improved; and all of them regained the weight that they had lost.

Several reasons may account for the weight gain associated with insulin therapy. First, insulin therapy quickly improves hyperglycemia. Such rapid improvement of glucose levels may lead to "insulin edema" with associated weight gain from fluid retention. With improvement of hyperglycemia, glycouria and calorie-wasting due to glycouria are eliminated. Unless the patient can burn off the excess calories retained due to improved glycemic control, weight gain may be the consequence of improved glycemic control. Insulin may also cause hypoglycemia, and the extra calories consumed by patients to treat hypoglycemic episodes may also contribute to weight gain. In addition, insulin is an anabolic hormone, and may indeed have appetite-stimulating effects.

Other mechanisms that may account for the weight gain associated with insulin therapy need to be explored. For example, recent studies have suggested that the amount of weight gain may be dependent on the type of insulin used. Further understanding of the differential effects of different insulins on weight gain may shed some light on this issue.

This activity is supported by an independent educational grant from Novo Nordisk.

2008-04-09T20:12:00.000-07:00

Pioglitazone Prevents Atherosclerosis Progression in Diabetics

News Author: Shelley Wood
Medscape Medical News

From American College of Cardiology (ACC) 57th Annual Scientific Session
From Heartwire — a professional news service of WebMD

April 2, 2008 (Chicago) — A new study of pioglitazone (Actos, Takeda Pharmaceuticals) suggests that it can prevent progression of atherosclerosis and produce meaningful improvements in cardiovascular risk factors over 18 months, as compared with glimepiride (Amaryl, Sanofi-Aventis) [1]. Experts say results of the Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation (PERISCOPE) trial, presented here at the American College of Cardiology 2008 Scientific Sessions, raise new questions about how best to lower blood sugar levels in type 2 diabetics.

Dr Steven Nissen (Cleveland Clinic, OH), who presented the results during a late-breaking trial session here, called the results a "huge surprise."

"What we saw was that the people who got one of the most widely used therapies — glimepiride, a sulfonylurea — had unequivocal progression of coronary atherosclerosis by [intravascular ultrasound] IVUS, while pioglitazone had a little less plaque at the end of the study, and the difference between the two therapies was highly statistically significant. . . . To our knowledge, this is first time that a diabetes study has been shown to slow progression of coronary atherosclerosis."

Nissen emphasized that while no one study should change clinical practice, particularly one based on a surrogate end point — in this case, atherosclerosis progression as measured by IVUS.

The trial did not address impact on clinical events. But Nissen also pointed out that the PERISCOPE results come in the wake of the PROspective pioglitazone Clinical Trial In macroVascular Events (PROACTIVE), which showed a nonsignificant 10% reduction in its primary end point of all macrovascular events and a significant 16% reduction in its secondary end point of death, myocardial infarction (MI), and stroke with pioglitazone. "I think the totality of information suggests this is a beneficial therapy, but PERISCOPE alone doesn't answer all the questions," he said.

But commenting on the study for heartwire, Dr Roger Blumenthal (John Hopkins University, Baltimore, MD) warned against making too much of a small imaging study on top of a larger clinical trial that failed to meet its primary end point. "We need more supportive data. Right now the totality of evidence is not enough to change guidelines," he said. "The chance of this having a significant impact on clinical practice is the same as a snowball's chance in Hades."

The PERISCOPE results have also been published online March 31, 2008 in the Journal of the American Medical Association.

2008-04-09T20:10:00.000-07:00

Soy Intake May Benefit Patients With Type 2 Diabetes and Nephropathy

News Author: Laurie Barclay, MD
Medscape Medical News

April 3, 2008 — Intake of soy protein had beneficial effects on cardiovascular risk factors and kidney-related biomarkers in patients with type 2 diabetes and nephropathy, according to the results of a longitudinal, randomized trial published in the April issue of Diabetes Care.

"Several short-term trials on the effect of soy consumption on cardiovascular risks are available, but little evidence exists regarding the impact of long-term soy protein consumption among type 2 diabetic patients with nephropathy," write Leila Azadbakht, PhD, from the Isfahan University of Medical Sciences in Isfahan, Iran, and colleagues. "To determine the effects of long-term soy consumption on cardiovascular risks, we measured C-reactive protein (CRP) and kidney function indexes among type 2 diabetic patients with nephropathy."

Of 41 patients with type 2 diabetes and nephropathy who were enrolled in this study, 18 were men and 23 were women. The soy protein group (n = 20) was assigned to a diet containing 0.8 g protein/kg body weight (35% animal proteins, 35% textured soy protein, and 30% vegetable proteins), whereas the control group(n = 21) was assigned to a similar diet containing 70% animal proteins and 30% vegetable proteins. Duration of the study was 4 years.

The soy protein group fared better than the control group regarding effects on cardiovascular risk factors. Mean change in the soy protein vs control groups for fasting plasma glucose levels was–18 ± 3 vs 11 ± 2 mg/dL (P = .03); for total cholesterol levels,–23 ± 5 vs 10 ± 3 mg/dL (P =.01); for low-density lipoprotein (LDL) cholesterol levels, –20 ± 5 vs 6 ± 2 mg/dL (P = .01); and for serum triglyceride levels, –24 ± 6 vs –5 ± 2 mg/dL (P = .01).

Compared with the control group, the soy protein group also had greater decreases in serum CRP levels (1.31 ± 0.6 vs 0.33 ± 0.1 mg/L; P = .02) and significant reductions in proteinuria (–0.15 ± 0.03 vs 0.02 ± 0.01 g/day;P = .001) and urinary creatinine levels (–1.5 ± 0.9 vs 0.6 ± 0.3 mg/dL; P = .01).

Limitations of the study include evaluation of only CRP rather than other inflammatory markers, evaluation of only a single dosage range and formulation of soy protein, lack of data on the effects of soy protein according to estrogen receptor genotype, and measurement of urinary urea nitrogen and urinary creatinine as concentrations rather than as 24-hour excretions.

"Longitudinal soy protein consumption significantly affected cardiovascular risk factors and kidney-related biomarkers among type 2 diabetic patients with nephropathy," the study authors write. "As diabetic nephropathy is a progressive disease, we expected that the conditions of these patients would have gotten worse after 4 years, but because of medical and dietary control, their conditions improved in some respects."

The costs of publication of this article were defrayed in part by the payment of page charges, mandating that it must therefore be hereby marked "advertisement" solely to indicate this fact.

Diabetes Care. 2008;31:648-654.

2008-04-09T20:08:00.000-07:00

Diabetic Ulcer Gel Linked to Increased Cancer Death

by Yael Waknine
Medscape Medical News

March 28, 2008 — A safety review of becaplermin gel (Regranex, Johnson & Johnson) is being conducted after study results suggested an increased risk for cancer-related mortality, the US Food and Drug Administration (FDA) warned healthcare professionals yesterday.

In the study, a health insurance database was used to identify 2 groups of diabetic patients aged 19 years and older with similar diagnoses, drug use, and use of health services from January 1998 through June 2003. One group had been prescribed becaplermin gel, and the other had not.

Analysis revealed an overall increase in the number of cancer deaths among patients who had been prescribed the gel 3 or more times for diabetic foot and leg ulcers. Insufficient information was available to determine whether there was an increase in the incidence of new cancers, the FDA said.

The findings supported those of a long-term study completed by the manufacturer in 2001, which also showed more cancers in patients using becaplermin compared with those who did not.

While the review is ongoing, the FDA recommends that healthcare professionals discuss the potential risks and benefits of becaplermin gel with their patients, according to an alert issued by MedWatch, the FDA’s safety information and adverse event reporting program.

Becaplermin 0.01% gel is a recombinant form of human platelet–derived growth factor that is indicated for the treatment of lower extremity diabetic neuropathic ulcers with an adequate blood supply that extend into the subcutaneous tissue or beyond.

Adverse events associated with use of becaplermin gel should be reported to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, MD 20852-9787.

Related Links
Resource Centers
Adverse Drug Events Reporting Resource Center
Diabetic Microvascular Complications Resource Center

2008-04-02T13:00:00.000-07:00

Aerobic Exercise Boosts Peripheral Insulin Sensitivity in Type 2 Diabetics

By Megan Rauscher

NEW YORK (Reuters Health) Mar 27 - The improvement in whole-body insulin sensitivity seen in type 2 diabetics who engage in aerobic exercise is due to gains in peripheral, not hepatic, insulin sensitivity, study findings indicate.

Dr. Jason J. Winnick from the department of molecular physiology at Vanderbilt University Medical Center, Nashville, and colleagues at Ohio State University, Columbus, determined the effect of 7 days of aerobic exercise training on peripheral and hepatic insulin sensitivity in 18 obese, mildly diabetic adults.

As reported in the Journal of Clinical Endocrinology and Metabolism for March, all study subjects discontinued their diabetes medications and then maintained an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 days.

During the second week, 9 randomly selected subjects also walked on a treadmill for 50 minutes daily at 70% of maximum oxygen consumption. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after the first dietary control week and a second clamp after completing the second week.

Dr. Winnick told Reuters Health, "In response to our 1-week exercise training protocol that involved moderate intensity walking, there was a fairly large increase in insulin's ability to stimulate glucose uptake by the whole body (i.e., whole-body insulin sensitivity) and muscle (i.e., muscle insulin sensitivity). However, within the same time frame, the exercise training did not improve insulin's ability to stimulate decreases in liver glucose production."

It is likely, the researcher added, that in the absence of caloric restriction, it takes more than a week to improve hepatic insulin sensitivity in people with diabetes.

It is also worth noting, Dr. Winnick said, that, despite discontinuation of diabetes medications, the fasting blood glucose values did not change over the intervention period -- so glucose metabolism can improve within one week of starting an exercise program.

"In particular, blood glucose after a meal may be improved due to improved muscle glucose uptake, despite not showing a change in the fasting blood glucose level," Dr. Winnick explained.

J Clin Endocrinol Metab 2008;93:771-778.

2008-04-02T12:59:00.000-07:00

Skin Test Predicts Microvascular Complications in Diabetes

NEW YORK (Reuters Health) Mar 25 - Skin autofluorescence measurements can noninvasively identify type 2 diabetic patients at risk of developing microvascular complications, Dutch researchers report in the March issue of Diabetes Care.

Dr. Esther G. Gerrits of Isala Clinics, Zwolle and colleagues note that the approach reflects the level of tissue accumulation of advanced glycation end products (AGEs), which are indicative of cumulative glycemic and oxidative stress.

The method has already been of use in assessing total and cardiovascular mortality risk in diabetic patients, and the researchers now examine its utility in identifying those at risk of microvascular complications.

At baseline, the team used an autofluorescence meter to evaluate 973 patients with well-controlled diabetes. Follow-up at a mean of 3.1 years in 881 surviving patients showed that autofluorescence at baseline was significantly higher in patients who developed any microvascular complication, neuropathy, or microalbuminuria.

Baseline autofluorescence measurements were not predictive of the development of retinopathy. Diabetes duration at baseline was the only significant predictor of this complication.

The researchers call for further study and longer follow-up, but conclude that this "noninvasive and time-saving application makes the autofluorescence reader an easy clinical tool that is useful in the outpatient clinic in risk assessment."

Summing up, Dr. Gerrits told Reuters Health that skin autofluorescence "seems to play an important role in certain patient groups like diabetes mellitus or patients receiving hemodialysis. Skin autofluorescence is related to and predictive for morbidity and mortality in these patient groups."

Diabetes Care 2008;31:517-521.

Related Links
Resource Centers
Diabetic Microvascular Complications Resource Center

2008-04-02T12:58:00.000-07:00

Simvastatin and Fenofibrate Better Than Either Alone for Mixed Dyslipidemia in Diabetics

NEW YORK (Reuters Health) Mar 24 - Combination therapy with simvastatin and fenofibrate is better than monotherapy with either drug for treating mixed dyslipidemia in patients with type 2 diabetes, according to a report in the February 15th American Journal of Cardiology.

"I believe every diabetic should be initially treated with a statin, with an LDL goal of at least 100 and probably even 70 would be better," Dr. Joseph Brent Muhlestein told Reuters Health. "I secondarily also look at triglycerides and HDL. I then target additional lipid therapy based on which of these three lipid values remain the most off-goal."

Dr. Muhlestein from the Intermountain Medical Center and LDS Hospital, Salt Lake City, Utah and associates investigated the effects of simvastatin alone, fenofibrate alone, and the combination of simvastatin and fenofibrate on lipid subparticles in 498 patients with type 2 diabetes without coronary heart disease.

Combination therapy reduced dense VLDL cholesterol significantly more than did fenofibrate or simvastatin monotherapy, the investigators found. Simvastatin lowered intermediate density lipoprotein (IDL) cholesterol significantly more than did fenofibrate.

The percentage of LDL cholesterol pattern B constituting total LDL cholesterol was significantly reduced by fenofibrate (a 13.7% reduction) and by the combination (an 11.1% reduction), but not by simvastatin.

Similarly, fenofibrate and the combination (but not simvastatin) significantly increased the percentage of buoyant LDL cholesterol constituting total LDL cholesterol.

"Thus," the investigators say, "fenofibrate and combination therapy favored the shift from LDL cholesterol pattern B to the more buoyant, less atherogenic LDL cholesterol."

Patients with higher triglyceride levels tended to experience greater reductions in LDL cholesterol pattern B and dense VLDL cholesterol with treatment, the researchers note.

"Diabetic dyslipidemia appears to be a very important contributor to the overall cardiovascular risk associated with diabetes," Dr. Muhlestein explained. "This risk comes from the combination of elevated LDL, elevated triglycerides, and low HDL. Aggressive treatment of this mixed dyslipidemia may be very important in saving the lives of our diabetic patients."

"We are now testing a possible benefit of triple drug lipid therapy in diabetics, comparing the double combination of simvastatin + fenofibrate with the triple combination of simvastatin + ezetimibe + fenofibrate," Dr. Muhlestein commented.

Am J Cardiol 2008;101:486-489.

2008-04-02T12:57:00.000-07:00

Metformin May Delay Onset of Diabetes in At-Risk Subjects

NEW YORK (Reuters Health) Mar 24 - In non-diabetics who are at risk for developing diabetes, treatment with metformin leads to modest improvements in weight, lipid profiles and fasting glucose, and substantial reductions in insulin resistance and new-onset of diabetes, results of a meta-analysis indicate.

Dr. Shelley R. Salpeter from Stanford University School of Medicine, California and colleagues pooled data from 31 trials that compared metformin with placebo or no treatment in 4570 adults at risk for diabetes followed for 8267 patient-years.

Metformin treatment, compared with placebo or no treatment, reduced body mass index by 5.3%, fasting glucose by 4.5%, fasting insulin by 14.4%, and calculated insulin resistance by 22.6%, according to the report in the February issue of the American Journal of Medicine.
Metformin treatment also reduced triglycerides and LDL cholesterol by 5.3% and 5.6%, respectively, and increased HDL cholesterol by 5.0% compared with placebo or no treatment.
"The incidence of new-onset diabetes was reduced by 40% (odds ratio, 0.6), with an absolute risk reduction of 6%, during a mean trial duration of 1.8 years," the investigators found.

Dr. Salpeter and colleagues think metformin could be added to diet and exercise if these lifestyle modifications alone are not sufficient to reduce the risk of diabetes in at-risk individuals.

"Future long-term trials will be needed to show that the metabolic benefits of metformin treatment result in a reduction in cardiovascular morbidity and mortality," they conclude.

Am J Med 2008;121:149-157.

2008-04-02T12:55:00.000-07:00

Weighing Up the Cardiovascular Benefits of Thiazolidinedione Therapy: The Impact of Increased Risk of Heart Failure

from European Heart Journal
Posted 03/25/2008
Erland Erdmann; Robert G. Wilcox

Abstract

Type 2 diabetes and heart failure commonly occur together and this combination is associated with poor outcomes. The relationship is likely to be multifactorial and also may involve a specific, though ill-defined, diabetic cardiomyopathy. Glucose-lowering therapies may also be associated with an increased risk of heart failure. Data from recent large-scale clinical trials have drawn particular attention to the thiazolidinediones that appear to increase the risk of heart failure in patients with type 2 diabetes. Although pioglitazone therapy has been shown to decrease the risk of macrovascular events, the overall cardiovascular benefit needs to be addressed together with the apparent increase in heart failure risk. In this review, we provide appropriate context for assessing this balance from several perspectives. First, we consider the high underlying risk of heart failure already present in type 2 diabetes. Secondly, we highlight a potential distinction between genuine heart failure due to cardiac dysfunction and thiazolidinedione-associated oedema that may simply unmask previously undiagnosed cardiac dysfunction without itself having any direct impact on heart muscle. Most importantly, we emphasize the apparent lack of any long-term mortality consequences and a relative improvement in outcomes associated with thiazolidinedione-induced ‘heart failure’ and discuss the potential mechanisms underlying this apparent paradox. Finally, we review the current guidelines for thiazolidinedione use and heart failure and suggest potential future strategies for avoiding and/or minimizing this association.

Eds note: details on the complete study can be found here

2008-04-02T12:50:00.000-07:00

Drug company-funded study finds drugs Actos and Amaryl can slow arterial disease

Tuesday, April 01, 2008
by Harlan Spector
Plain Dealer Reporter

CLEVELAND - Doctors say they have shown for the first time that a diabetes drug can prevent the progression of coronary heart disease.

The Cleveland Clinic-led study involved 543 patients with Type 2 diabetes. It compared two drugs, Actos and Amaryl, which act in opposite ways: Actos is part of a newer class of drugs that reduce insulin resistance, while Amaryl is an older drug that increases insulin production.

Using intravascular ultrasound, researchers found that after 18 months, Actos was significantly better at reducing progression of plaque buildup in arteries of the heart.

"Seventy-five percent of diabetics will die of a cardiovascular-related cause," study leader Dr. Steven Nissen, the Clinic chief of cardiovascular medicine, said in an interview Monday. "If you can find a therapy that reduces progression of heart disease and atherosclerosis, that will potentially have a very big impact."

The study is published in Wednesday's Journal of the American Medical Association. Results were released Monday, after presentation at the American College of Cardiology scientific conference in Chicago.

Previous studies have shown that Actos may lower the risk of heart attack and stroke. The drug also carries increased risk of heart failure and bone fractures.

The question of whether blood-sugar control can reduce heart disease has been controversial, an editorial that accompanied the study said. Part of a federally sponsored trial was stopped this year, after an unexpected number of patients died while undergoing aggressive therapy to lower blood sugar.

Warnings have also been raised about the diabetes drug Avandia -- a chemical relative of Actos -- after Nissen last year tied Avandia to increased risk of heart attack.

Doctors said the new results suggest that lowering blood sugar may not be as important for heart health as the choice of drug.

"There's clearly more to the story than just getting the sugars down," said Dr. Emil Hayek, medical director of Akron General Medical Center's Heart and Vascular Center. "I think it should change clinical practice. There's clearly a benefit to using some of the more novel ways to treat diabetes."

Hayek said the results suggest Actos may prevent heart attacks and strokes, but "that's a much more difficult question to answer."

Takeda Pharmaceuticals North America Inc., which makes Actos, paid for the study.

2008-03-31T14:28:00.000-07:00

Researchers find six more diabetes genes: study

by Michael Kahn
Sun Mar 30, 1:05 PM ET

LONDON (Reuters) - U.S. and European scientists have found six more genes that make people more susceptible to developing type 2 diabetes, in a study they say may help prevent and treat the chronic condition.

The finding extends the total number of genes linked to the disease to 16 and provides clues to how the biological mechanisms that control blood sugar levels go awry when people get type 2 diabetes, the researchers said.

"None of the genes we have found was previously on the radar screen of diabetes researchers," said Mark McCarthy, a diabetes researcher at the University of Oxford, who co-led the study.

"Each of these genes therefore provides new clues to the processes that go wrong when diabetes develops, and each provides an opportunity for the generation of new approaches for treating or preventing this condition."

A diabetic's blood glucose levels tend to rise too high. Too much glucose in the blood can damage the eyes, kidneys and nerves, and lead to heart disease, stroke and limb amputations.

Type 2 diabetes accounts for about 90 percent of all diabetes cases and is closely linked to obesity and physical inactivity. The World Health Organisation estimates that more than 180 million people worldwide have diabetes -- a number likely to more than double by 2030.

In the study published in Nature Genetics, researchers from over 40 centers analyzed the genetic data of more than 70,000 people. The team turned up six genetic differences that each individually slightly raise a person's risk of diabetes.

But the risk for the few people unlucky enough to inherit all six variations is two to three times higher than the average risk, McCarthy said in a telephone interview.

"By getting a handle on the mechanisms involved in disease we can start to tackle them in a more systemic and scientific way," he said.

One of the surprising finds was the link between type 2 diabetes and a gene called JAZF1, which researchers recently showed plays a role in prostate cancer, the researcher added.

The researchers believe the genes -- which also include the CDC123-CAMK1D, TSPAN8-LGR5, THADA, ADAMTS9 and NOTCH2 genes -- are involved in regulating the number of insulin-producing cells in the pancreas, McCarthy said.

2008-03-31T14:27:00.000-07:00

Breath Test for Diabetes

POSTED: 12:25 pm EDT March 30, 2008
Source: http://www.news4jax.com/health/15744938/detail.html

It's painful, invasive, and time-consuming, yet every day -- many times a day -- millions of diabetics draw blood to check their blood sugar levels. But there may soon be a way to monitor those levels without ever touching the skin.

14-year-old Robbie Mansfield pricks his finger seven times a day. That means this young baseball fan tests his blood sugar 2,555 times a year. But now, there may be a painless way to collect those numbers.

Doctor Pietro Galassetti thinks he's found it. Dr. Galassetti collected breath samples from diabetic children while blood sugar levels were high and as levels fell in response to insulin. Using a technique developed to test air pollution, chemists detected high concentrations of methyl nitrate -- a byproduct of the damage to body tissue -- when blood sugar levels are too high.
And we saw that the children who had high blood sugar had very high methyl nitrate in their breath and then as we gradually corrected the blood sugar, the methyl nitrate in their breath was coming down," says Pietro Galassetti, M.D., a diabetes researcher at the University of California, Irvine Medical Center in Irvine, Calif.

While still five to ten years off, Dr. Galasetti sees a hand-held breath analyzer replacing the standard blood test.

"Not having to stop and test his blood -- just be able to blow into a canister or whatever. It'll be amazing," Robby's mom, Julie, says.

"It would be a lot easier. I could have more of a normal life without having to step out every couple of hours to test my blood sugar," Robby says.

If it's easy, kids are more likely to do it. Controlling glucose levels now lowers Robby's chance of complications down the road … and increases his shot at the big leagues.

Breath analysis has already shown promise in diagnosing ulcers and cystic fibrosis. Dr. Galassetti says eventually, we may be able to monitor insulin and cholesterol with a breath test.

FOR MORE INFORMATION, PLEASE CONTACT:
University of California,
Irvine Pietro Galassetti, M.D.
pgalasse@uci.edu

UCI Medical Center
101 The City Dr.
Building 25, 2nd Floor

2008-03-31T14:22:00.000-07:00

Diabetes seen as 'cultural genocide'

The Press Source: Diabetes NZ
Monday, 31 March 2008

His prediction that Maori and many other indigenous people were threatened with `extinction' from diabetes caused an international outcry. But Australian expert Professor Paul Zimmet tells RUTH HILL he stands by his prognosis.

In the 10 seconds it takes you to scan these first few paragraphs, one person will die from diabetes somewhere in the world.

Professor Paul Zimmet, director of Monash University's International Diabetes Institute, says the world is facing "the biggest epidemic in history" fuelled by growing obesity rates.

When he and Wellington-based epidemiologist and cardiologist Dr Ian Prior started talking about a diabetes epidemic 30 years ago, they were met with scepticism from doctors and politicians alike.

They had no idea how big it would get.

"Who could have anticipated that we would need bigger seats on planes, bigger stretchers in ambulances, bigger CAT scanners in hospitals because people are so much fatter?"

The obscene paradox is that while millions are still dying of malnutrition in the developing world, many more are dying of a surfeit of food.

At the International Diabetes Federation Western Pacific Region Conference, which begins in Wellington today, Zimmet will unveil the institute's forecast for the next 20 years.

There are about 250 million type 2 diabetics in the world -- two-thirds of them in the Asia-Pacific region -- and that figure is set to balloon to 390 million by 2025.

The alacrity with which people in non-Western nations have abandoned their traditional diets in favour of fatty, sugary foods, coupled with a decrease in physical activity, is a recipe for a health disaster.

In 1975, Prior was the first scientist to identify higher rates of diabetes among Pacific Islanders. Intrigued by the findings, Zimmet went to Nauru, where he found the highest rates in the world.
Maori and other Polynesians are more genetically susceptible to developing type 2 diabetes.

Furthermore, children who are exposed to high levels of glucose in the womb from diabetic mothers are at greater risk of developing diabetes in later life.

Zimmet's controversial 2006 claim that some ethnic populations -- including Maori -- were facing "cultural genocide" from diabetes made headlines around the world.

"Unfortunately that upset some Maori leaders," he says. "But it did open up a dialogue between us and we came to a very firm agreement that diabetes is a huge threat to Maori."

One in four indigenous adults in the Pacific and North America is affected by diabetes, and they are dying in droves due to kidney failure, cardiac disease and infections.

While the United Nations passed a rare unanimous resolution in 2006 recognising the disease as an international health problem, many developing nations are turning their backs on the diabetes tsunami as they face more immediately pressing concerns.

Zimmet's organisation estimates there will be 285,000 Kiwis with diabetes by 2025. He says the New Zealand Government should be commended for allocating $76 million over four years to fight obesity -- but he is wary of the cash being gobbled up by small local projects.

"These local interventions are great for small communities but they do not result in any widespread societal change," he said.

"There's no point beating people up for being overweight unless we change the environment that's making them fat."

Banning trans fats and informing children only goes so far; he wants better urban planning to create space to exercise.

He almost despaired recently when the education minister in Victoria asked parents not to send their children to school early because of the "liability issues" if they were hurt in the playground.
"We used to spend half an hour before school playing cricket or kicking around a football, but now mothers are driving their kids to the school gate in 4WDs," he said.

"Probably the best thing we could do is keep raising the price of petrol, which will force people to walk or cycle.

"This obesity epidemic is horrible, but the biggest tragedy is it's a preventable epidemic."

WEIGHTY BURDEN
Obesity rates doubled between 1988 and 2003.

One in three children (five-14) is overweight or obese.

500,000 adults are obese.

Obesity is linked to heart disease, stroke and type 2 diabetes.

About 142,000 have been diagnosed with type 2 diabetes, set to rise to 180,000 by 2011.

Type 2 diabetes cost taxpayers $540 million last year and will reach $2 billion by 2021.

The disease accounts for 20 per cent of all Maori deaths, and 4 per cent of non-Polynesian deaths.

Maori women are 10 times more likely and Maori men 6.5 times more likely to die from diabetes than non-Maori.

2008-02-07T01:50:00.000-08:00

Deaths halt part of diabetes-heart clinical trial

Study aimed to cut blood sugar of type 2 diabetics' at high risk of heart attack, stroke

WASHINGTON (AP) -- An unexpected number of deaths among patients receiving intense therapy to lower their blood sugar forced the National Institutes of Health to abruptly cut short part of a major study on diabetes and heart disease.

The therapy was aimed at reducing to normal levels the blood sugar of type 2 diabetics at especially high risk of heart attack and stroke. There were 257 deaths among people receiving intense diabetes treatment, compared with 203 in the standard treatment group, NIH's National Heart Lung and Blood Institute said.

More than 18 million Americans have diabetes, with type 2 the most common form.

Last fall the Food and Drug Administration added new warnings to the label of the popular diabetes drug Avandia, listing concerns about heart ailments. However, in Wednesday's announcement NHLBI officials stressed that they have been unable to link the increased deaths in the study to any drug, including Avandia.

Some 10,251 people were enrolled in the Action to Control Cardiovascular Risk in Diabetes, or ACCORD, study, with an average participation time of four years.

The participants were in groups receiving three types of treatment, intensive lowering of blood sugar, lowering blood pressure or reducing cholesterol.

"A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these especially high-risk patients with type 2 diabetes," said Dr. Elizabeth G. Nabel, director of the institute.

"Though we have stopped this part of the trial, we will continue to care for these participants, who now will receive the less-intensive standard treatment. In addition, we will continue to monitor the health of all participants, seek the underlying causes for this finding, and carry on with other important research within ACCORD," she said in a statement.

The study focuses on treatments for adults with type 2 diabetes, the most common form, who are at especially high risk for heart disease, meaning they had at least two risk factors, which include high blood pressure, high cholesterol, obesity and smoking.

Dr. William Friedewald, professor of Public Health and Medicine at Columbia University, and chairman of the ACCORD Steering Committee, said that there were "about 10 percent fewer nonfatal cardiovascular events such as heart attacks in the intensive treatment group compared to the standard treatment group. However, it appeared that, if a heart attack did occur, it was more likely to be fatal. In addition, the intensive treatment group had more unexpected sudden deaths, even without a clear heart attack."

The action was recommended by an independent advisory group of experts in diabetes, heart disease, epidemiology, patient care, biostatistics, medical ethics and clinical trial design that has been monitoring ACCORD since it began.

Participants will continue to receive blood sugar treatment from their study clinicians until the planned trial conclusion in June 2009.

Nabel stressed that diabetes patients should not change their treatment without consulting their doctor. The American Diabetes Association agreed and said it continues to encourage control of blood sugar in treatment of diabetes.

NHLBI said the intensive treatment group had a target blood sugar goal of less than 6 percent, which is similar to blood sugar levels in adults without diabetes. The standard treatment group aimed for a target similar to what is achieved, on average, by those with diabetes in the United States, of 7 to 7.9 percent.

2008-01-24T14:56:00.000-08:00

Obesity surgery seen as potential diabetes cure

Study: Bariatric surgery more likely than standard care to rid patients of diabetes

CHICAGO, Illinois (AP) -- A small new study gives the strongest evidence yet that obesity surgery can cure diabetes.

Obesity is a major risk factor for diabetes; rates for both are climbing.

Patients who had surgery to reduce the size of their stomachs were five times more likely to see their diabetes disappear over the next two years than were patients who had standard diabetes care, according to Australian researchers.

Most of the surgery patients were able to stop taking diabetes drugs and achieve normal blood tests.

"It's the best therapy for diabetes that we have today, and it's very low risk," said Dr. John Dixon of Monash University Medical School in Melbourne, Australia, lead author of the study, which involved 55 patients.

The surgery performed was stomach banding, a procedure more common in Australia than in the United States, where gastric bypass surgery, or stomach stapling, predominates.

Gastric bypass is even more effective against diabetes, achieving remission in a matter of days or a month, said Dr. David Cummings, who wrote an accompanying editorial in the journal but was not involved in the study.

"We have traditionally considered diabetes to be a chronic, progressive disease," said Cummings of the University of Washington in Seattle. "But these operations really do represent a realistic hope for curing most patients."

Diabetes experts who read the study said surgery should be considered for some obese patients, but more research is needed to see how long results last and which patients benefit most.

Surgery risks should be weighed against diabetes drug side effects and the long-term risks of diabetes itself, they said.

Experts generally agree that weight-loss surgery would never be appropriate for diabetics who are not obese, and current federal guidelines restrict the surgery to obese people.

The diabetes benefits of weight-loss surgery were known, but the Australian study in Wednesday's Journal of the American Medical Association is the first of its kind to compare diabetes in patients randomly assigned to surgery or standard care. Scientists consider randomized studies to yield the highest-quality evidence.

The study involved 55 patients, so experts will be looking for results of larger experiments under way.

"Few studies really qualify as being a landmark study. This one is," said Dr. Philip Schauer, who was not involved in the Australian research but leads a Cleveland Clinic study that is recruiting 150 obese people with diabetes to compare two types of surgery and standard medical care. "This opens an entirely new way of thinking about diabetes."

Obesity is a major risk factor for diabetes, and researchers are furiously pursuing reasons for the link as rates for both climb. What's known is that excess fat can cause the body's normal response to insulin to go haywire. Researchers are investigating insulin-regulating hormones released by fat and the role of fatty acids in the blood.

In the Australian study, all the patients were obese and had a diagnosis of type 2 diabetes during the previous two years. Their average age was 47. Half the patients underwent a type of surgery called laparoscopic gastric banding, where an adjustable silicone cuff is installed around the upper stomach, limiting how much a person can eat.

Both groups lost weight over two years; the surgery patients lost 46 pounds on average, while the standard-care patients lost an average of 3 pounds.

Blood tests showed diabetes remission in 22 of the 29 surgery patients after two years. In the standard-care group, only four of the 26 patients achieved that goal. The patients who lost the most weight were the most likely to eliminate their diabetes.

Both patient groups learned about low-fat, high-fiber diets and were encouraged to exercise. Both groups could meet with a health professional every six weeks for two years.

The death rate for stomach band surgery, which can cost $17,000 to $20,000, is about 1 in 1,000. There were only minor complications in the study. Stomach stapling has a 2 percent death rate and costs $20,000 to $30,000.

In the United States, surgeons perform more than 100,000 obesity surgeries each year.

The American Diabetes Association is interested in the findings. The group revises its recommendations each fall, taking new research into account.

"There is a growing body of evidence that bariatric surgery is an effective tool for managing diabetes," said Dr. John Buse of the University of North Carolina School of Medicine in Chapel Hill, the association's president for medicine and science.

"It's just a question of how effective is it, for what spectrum of patients, over what period of time and at what cost? Not all those questions have been answered yet."

Medical devices used in the study were provided by the manufacturers, but the companies had no say over the study's design or its findings, Dixon said.

All About Diabetes • Obesity

2008-01-11T09:51:00.000-08:00

Statins for all diabetics urged

BBC Online News
Friday, 11 January 2008

Millions of statins are prescribed annually in the NHSPeople with diabetes should receive cholesterol-busting drugs regardless of whether they have signs of heart disease, UK researchers say.

Statins cut the risk of heart attack, stroke and death in diabetic people even in those with low cholesterol levels, analysis of 14 trials shows.

It means hundreds of thousands more people could benefit from treatment, the Lancet report said.

There are 2.5 million people diagnosed with diabetes in the UK.

Many more do not realise they have the condition and statins are "underused" in people with diabetes the researchers said.

Guidance from the National Institute of Clinical and Health Excellence (NICE) in England and Wales issued in 2006 estimated around 3.3 million people are eligible for treatment with statins.
This includes people with diabetes who have a 20% risk of developing cardiovascular disease in the next 10 years.

Benefits

A team of researchers at Oxford University reviewed studies of more than 90,000 people - 19,000 with diabetes - and found that many more would benefit from statins than previously realised.

They found that standard daily treatment with statins would prevent about one third of heart attacks and strokes in people with diabetes.

The benefits were seen regardless of age, sex and whether patients were already showing signs of cardiovascular disease.

After five years, 42 fewer people with diabetes had major problems, such as heart attacks or stroke, for every 1,000 treated with statins.

The only exceptions for treatment should be those with exceptionally low risk, such as children or those who cannot take the drugs for other reasons, such as pregnant women.

Study leader Professor Colin Baigent said there had been some debate about whether statins would have the same benefits in people with diabetes as those with heart disease in general.
"People with diabetes are a clearly defined group of people at an increased risk of cardiovascular disease.

"What we're saying is statins are clearly effective in every type of person with diabetes."
Diabetes UK estimates 60% of all diabetics currently receive statins. That would mean the vast majority of the remaining 40% could also benefit from these drugs, according to the researchers.
However, Douglas Smallwood, chief executive of Diabetes UK, recommended statins for people with diabetes over the age of 40 or diabetics younger than 40 with another risk factor.

"Diabetes UK also strongly recommends that good diabetes management should rely not only on medication, but also on a healthy lifestyle and diet," he added.

2007-12-11T14:00:00.000-08:00

Canadian study finds heart risks with Avandia

Updated Tue. Dec. 11 2007 4:10 PM ET
CTV.ca News Staff

The popular diabetes medication Avandia is under scrutiny again. A new Canadian study finds that the drug, along with others like it, increases the risk of heart failure, heart attacks and death in older adults.

The study authors say their results provide further evidence that this class of medication may cause more harm than good.

The study, published in the Journal of the American Medical Association, looked at the glitazone class of drugs, which include rosiglitazone, the pharmaceutical name for Avandia and pioglitazone (sold under the name Actos). Both drugs work by increasing the body's sensitivity to insulin.

The researchers say this study is distinct from previous studies because it was not a clinical trial but the first real-world, population-based examination of the drugs.

The study examined Ontario health-care databases, looking for residents aged 65 years or older who were treated with diabetes medications and then followed them for almost four years, until March 2006.

During this time, 7.9 per cent of patients made a visit to the hospital for congestive heart failure, 7.9 per cent went to the hospital for a heart attack, and 19 per cent died. The researchers found that, compared to patients taking other diabetes medications, patients taking glitazones (Avandia & Actos) had:

A 60 per cent relative increase in heart failure,
A 40 per cent relative increase in heart attacks,
And a 30 per cent relative increase in death.

This translates into an estimated three additional episodes of heart failure, four additional heart attacks and five additional deaths for every 100 individuals taking these drugs, over a four-year period in the older population.

The researchers say the risk was found predominantly among those taking Avandia. They say the much small numbers of people taking Actos limited their ability to be certain about adverse events in patients taking that drug.

They also add that they cannot be sure whether similar results would be found in patients younger than 65. But lead author Dr. Lorraine Lipscombe, a researcher with the Institute for Clinical Evaluative Sciences, says her study presents a concern for older diabetic patients taking these drugs, since diabetics already have a higher risk of heart problems.

She also noted that seniors have the highest prevalence of diabetes and represent over 40 per cent of the population with the disease.

"We found that in this older group that the risks outweigh the benefits, and they should talk to their physicians about whether other alternatives should be considered," she told CTV News.

The study comes on the heels of the Food and Drug Administration in the U.S. deciding to slap a black box label warning on Avandia, telling patients that it may, or may not, increase the risk of heart attacks. It is the most severe type of warning the agency can require pending further research.

Co-author and senior ICES scientist Dr. David Alter says patients taking Avandia shouldn't panic.

"Treatment decisions must remain individualized with doctors and patients weighing the potential harms and benefits of these drugs, especially when used among the elderly who are at higher-risk of cardiac complications," he says.

Dr. Amir Hanna, deputy division head of endocrinology and metabolism at St. Michael's Hospital in Toronto and a member of the national board of the Canadian Diabetes Association, says he still believes that Avandia and other glitazones have a role to play in treating diabetes.

"We have to choose our patients well. We have to balance the pros and cons of each drug," he says.

"Older people who have underlying kidney and heart disease would not be good candidates for Avandia... For other people who are healthy, early on in the course of the disease, it is safe -- either by itself or in combination with metformin."

GlaxoSmithKline (GSK), the makers of Avandia, disagrees with the new study, saying it has "significant limitations and generates misleading conclusions." They add that larger U.S.-based studies have found "no consistent or systematic evidence that rosiglitazone increases the risk of (heart attacks) or death in comparison to other anti-diabetic agents."

GlaxoSmithKline has agreed to do a longer-term study comparing the drug to other medications, but those results won't be available for another six years.

There were 1.2 million prescriptions for Avandia issued in Canada during the past year, according to IMS Health Canada, a private company that tracks prescription drug sales.

In November, GSK issued new restrictions on the use of the drug, in consultation with Health Canada. Among the restrictions, they said it should not be taken by patients with any stage of heart failure.

The authors suggest those restrictions don't go far enough.

"Our findings argue against current labeling of (glitazones) that warns against use only in persons at high risk of (congestive heart failure), as we did not identify any subgroup of older diabetes patients who may be protected from adverse effects of (glitazones)," the authors write.

As for whether Avandia should be pulled from Canadian pharmacies, Lipscombe was not prepared to say.

"Experts from regulatory bodies such as Health Canada and the Food and Drug Administration will have to consider our findings in the context of all the evidence so far, to decide the future of these drugs," she said in a statement.

2007-11-18T07:01:00.000-08:00

New Edmonton diabetes institute houses world's top researchers

12-year-old diabetic's grandfather donated $1 million to support construction

Wednesday, November 14, 2007

CBC News

EDMONTON - Canada's largest diabetes research centre opened in
Edmonton Wednesday, bringing the world's leading
researchers under one roof to find new ways of
preventing, treating and ultimately curing the disease.

The Alberta Diabetes Institute recruited Dr. Ronald
Gill from a top post at the University of Colorado to
be the new facility's scientific director.

The Alberta Diabetes Institute brings leading
researchers under one roof.
(CBC) "This group has a large number of Type 1 and Type
2 diabetes researchers, which is very, very rare
anywhere in the world," Gill said.

Diabetes leaves the body unable to produce its own
insulin, a hormone that regulates sugar in the blood.

More than 1,000 cases of diabetes are diagnosed every
month in Alberta. It's estimated treating diabetes and
its complications in Canada costs about $10 billion
ever year.

The $300-million institute at the University of Alberta
was built with both public and private funding.

Don Hamilton, an investor in the Edmonton Oilers,
donated $1 million to support the construction because
he wants to see his granddaughter continue playing
competitive soccer.

'Now scientists have an actual building where they can
actually do the work and help people like me lead a
normal life.' —Margaret Hamilton-Lane, 12, Type 1 diabeticMargaret
Hamilton-Lane, 12, is one of 250,000 Albertans
suffering from Type 1 or Type 2 diabetes. She's excited
about the prospect of a cure being found in Edmonton.

"I really want to see what they can do because now
scientists have an actual building where they can
actually do the work and help people like me lead a
normal life," she said.

Hamilton-Lane already benefits from advances in
diabetes treatment. She wears a high-tech insulin pump
the size of a pager clipped onto her belt and connected
to her stomach with a tiny tube. The pump constantly
measures her blood sugar, which means she doesn't need
to prick her finger with a needle for a test every few
hours.

Edmonton Protocol was major diabetes breakthroughEdmonton proved to be a pioneer in diabetes research
when a team from the University of Alberta isolated
islets, clusters of insulin-producing cells from the
pancreas, and transplanted them into the livers of
patients with Type 1 diabetes in 1999.

The procedure, known as the Edmonton Protocol, frees
most patients from the need for daily injections and is
hailed as the biggest advance in research since the
discovery of insulin.

The institute at the corner of 112 Street and 87 Avenue
will house researchers as well as support staff,
doctors and nutritionists.

"There's just no substitute for having people in a
micro-environment where the things are happening, where
they can actually see each other, give seminars, do
collaborative projects, sometimes sit down, have coffee
and just talk about ideas, so the location is really
important," said Gill.

2007-11-14T17:16:00.000-08:00

British schools 'failing' diabetic pupils

BBC News
Last Updated: Wednesday, 14 November 2007, 00:01 GMT

Schools are not giving pupils with diabetes the support they need and are demanding parents come in to treat their child, charities claim.

Some 70% of 2,500 schools surveyed by a coalition of diabetes charities said that when pupils could not inject themselves, parents were asked to help.

Diabetic children were also missing out on school trips, the charities said.

The report follows a study which said 83% of children with diabetes are not achieving recommended glucose levels.

This puts them at risk of a range of complications from Type 1 diabetes, including unconsciousness, fits and comas, as well as more serious longer term problems such as blindness, amputation and kidney disease.

Diabetes UK, the Juvenile Diabetes Research Foundation, support group Input and UK Children with Diabetes Advocacy Group have put together a series of recommendations.

They said while care plans did exist, schools needed to invest more in the training of staff in diabetes care and where necessary bring in outside staff who can administer injections.

Although 50% of the Local Education Authorities (LEAs) surveyed said they had funding for diabetes care, only 30% of schools knew that some form of financial support might be available.

It is simply not acceptable, the charities argue, that parents - often mothers - are having to give up work to attend to their child, and unfair on the child as it may isolate them from school life.

Numbers rising

"This research confirms what too many parents have been telling us - that children with diabetes get a raw deal at school," said Douglas Smallwood, chief executive of Diabetes UK.

Karen Addington, head of JDRF, said: "Diabetes is a legally recognised disability and all children with Type 1 diabetes have the right to appropriate onsite care to enable them to take part in a full school life, including extra-curricular activities."

The National Union of Teachers said it fully supported the recommendations and would welcome provision for extra training.

However it stressed that it would always be up to the individual teacher to decide whether to help with injections, as this was not in his or her professional remit.

"What's key is that schools draw up individual care plans for pupils with diabetes so everyone knows what they are doing," said a spokeswoman.

A spokesperson from the Department for Children, Schools and Families added that pupils "with medical conditions, including diabetes, should not be prevented from taking part in school trips or participating in school sports.

"We have issued specific guidance to schools to plan effectively for trips and to adapt teaching of sports to meet individual needs. We also recommend schools should consult with parents and professionals so that pupils with diabetes can be involved."

The number of children with Type 1 diabetes is rising, with some studies suggesting it is increasing across Europe at a rate of 2-3% each year.

The reasons for this are unclear, but there has been some speculation that it may be linked to children's immune system not getting adequate exposure as a result of modern standards of hygiene.

According to the latest figures from information registered by GPs, the number of people in Britain diagnosed with diabetes has shot up by 100,000 in just the last year.

A total of 2.3 million Britons are now diagnosed diabetics, and the vast majority have the Type 2 disease. A further 750,000 are believed to have Type 2 diabetes without knowing it.

2007-11-14T04:33:00.000-08:00

Diabetes Communities Unite to Celebrate World Diabetes Day November 14

Leading Diabetes Organizations Join Forces to Fight Diabetes as World Diabetes Day

NEW YORK, NY (Nov. 5 2007) - Diabetes currently affects 246 million people globally, including nearly 21 million children and adults in the United States. For all of them and the many millions more at risk, November 14, 2007 is a highly significant date as it marks the first United Nations-observed World Diabetes Day.

The International Diabetes Federation (IDF), who leads the campaign, will be joined by the American Diabetes Association (ADA), the Juvenile Diabetes Research Foundation (JDRF), and many other organizations to mark the day in celebrations throughout the United States.

World Diabetes Day is the primary global awareness campaign of the diabetes world. It was introduced by IDF and the World Health Organization in response to concern over increasing numbers of people with diabetes around the world. The date marks the birthday of Frederick Banting who, along with Charles Best, first conceived the idea which led to the discovery of insulin in 1921. With the passage of the United Nations' World Diabetes Day Resolution in December 2006, November 14 has now become a United Nations-observed day.

Thousands of New Yorkers will join the millions of people worldwide who will use the day to raise awareness of diabetes and its serious complications. IDF has planned a host of activities throughout the city. These include the formation of a human blue circle on the grounds of the United Nations - the blue circle is the global symbol for diabetes; a 246-step march from the UN down 1st Avenue in honor of people with diabetes worldwide; and a diabetes education rally that will include musical performances and celebrity appearances. As the sun sets on World Diabetes Day, over 120 iconic sites and buildings around the world will light up in blue to mark the day.

Monuments in the US include the Empire State Building in New York, Sears Tower in Chicago, Prudential Tower in Boston, Los Angeles Airport (LAX) in Los Angeles, the Soldiers' and Sailors' Monument in Indianapolis, the Four Freedoms Monument in Evansville, San Francisco City Hall and Coit Tower in San Francisco, Qwest Stadium in Seattle and the Naismith Memorial Basketball Hall of Fame in Springfield.

Professor Martin Silink, President of the International Diabetes Federation explained the significance of the lightings: "These landmarks are lighting up as beacons of hope for the 246 million people living with diabetes worldwide. The illumination of so many landmarks is a prominent statement to governments everywhere: the global diabetes epidemic can no longer be ignored."

American Idol finalist and recording artist Elliott Yamin, who has type 1 diabetes, will perform "Promise to Remember Me," a song written for JDRF by Grammy-award winning composer Alan Silvestri and lyricist Steven Schwartz. He will be joined in song at the U.N.'s Rose Garden opening ceremony by children with diabetes. Restaurateur and television host B. Smith will emcee the Diabetes Education Rally and lead hundreds of World Diabetes Day supporters. This inspirational and educational event follows the 246-step march from the U.N. building to Guastavino's restaurant under the 59th Street Bridge, with each step representing one million people with diabetes.

Dr. Francine Kaufman, who leads the campaign to raise awareness of diabetes in children, the theme of this year's World Diabetes Day hopes that increased awareness of diabetes can lead to improved care: "The United Nations now recognizes diabetes as a serious disease that poses severe risks for families, countries and the entire world. Governments everywhere have now acknowledged the negative effect on economies and development. We now need individuals to appreciate the risks of diabetes and understand what can be done to control the disease and prevent or delay its life-threatening complications."

New York's Mayor Michael Bloomberg and Governor Eliot Spitzer, Chicago's Mayor Richard Daley, Los Angeles' Mayor Antonio R. Villaraigosa, and the Mayor of St. Louis, Francis Slay among others, have all officially proclaimed November 14 as World Diabetes Day in their respective cities. City and town officials throughout the country have responded to the need to recognize the day and the significance of diabetes for so many Americans.

This first U.N.-observed day is a result of the landmark resolution recognizing that diabetes presents as great a threat to global health as HIV/AIDS, tuberculosis and malaria.
For more details on World Diabetes Day and events around the U.S., please visit www.worlddiabetesday.org

About IDF
The International Diabetes Federation (IDF) is an organization of over 200 member associations in more than 160 countries. Its mission is to promote diabetes care, prevention and a cure worldwide. IDF is a non-governmental organization in official relations with the World Health Organization and is associated with the Department of Public Information of the United Nations. Visit www.idf.org .

About ADA
The American Diabetes Association is the nation's premier voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. In 2006, the Association provided a record $43.3 million toward funding research to combat type 1 and type 2 diabetes in all people of ages and races. For more information on diabetes, please visit www.diabetes.org or call 1-800-DIABETES (1-800-342-2382). Information from both these sources is available in English and Spanish.

About JDRF
JDRF was founded in 1970 by the parents of children with type 1 diabetes - a disease that strikes children, adolescents, and adults suddenly, makes them insulin dependent for life, and carries the constant threat of devastating complications. Since inception, JDRF has provided more than $1.16 billion to diabetes research worldwide. More than 85 percent of JDRF's expenditures directly support research and research-related education. JDRF's mission is constant: to find a cure for diabetes and its complications through the support of research. For more information on type 1 diabetes, please visit www.jdrf.org .

-----------------------

MEDIA CONTACTS:
Kerrita McClaughlyn, IDF, +32-487530625, media@idf.org
Angela Russo, ADA, (800) 676-4065 ext. 3425, arusso@diabetes.org
Joana Casas, JDRF, (212) 479-7560, mcasas@jdrf.org
Download Press Release (PDF)

2007-11-14T04:30:00.000-08:00

Global landmarks mark first United Nations World Diabetes Day

BRUSSELS, BELGIUM (Nov. 12 2007) - On November 14th over 200 landmarks will light up in blue to mark the first United Nations-observed World Diabetes Day. Included among them are many of the world's most iconic buildings and sites. The landmarks will light up the skyline in the blue colour of the diabetes circle, the global symbol for diabetes.

The Empire State Building, one of New York's most famous landmarks, was the first building to join the World Diabetes Day campaign and agree to light up in blue. Since then the campaign has been joined by some of the world's most famous landmarks, including the Sydney Opera House, the London Eye, Leaning Tower of Pisa, Tokyo Tower, Niagara Falls, the Burj Al Arab in Dubai, the Aleppo Citadel in Syria, the Obelisk in Buenos Aires, the Sears Tower in Chicago, Christ the Redeemer in Brazil, and the building currently considered the world's tallest: the Taipei 101 Tower in Taiwan.http://www.worlddiabetesday.org/bluemonuments

Professor Martin Silink, President of the International Diabetes Federation (IDF), the organization that leads the World Diabetes Day campaign explained the significance of the lightings: "These buildings are lighting up as beacons of hope for the 246 million people living with diabetes worldwide. The illumination of so many landmarks is a prominent statement to governments everywhere: the global diabetes epidemic can no longer be ignored."

The UN-recognition of World Diabetes Day follows the passage of Resolution 61/225 in December 2006. The resolution was the first milestone of an ambitious campaign led by IDF to raise awareness of diabetes and its serious complications. The World Diabetes Day Resolution recognizes diabetes as a chronic, debilitating and costly disease that poses severe risks for families, countries and the entire world. The UN has thrown its support behind World Diabetes Day and encourages countries to act now to reverse the diabetes epidemic.

Today, 246 million people live with diabetes globally. If nothing is done, this figure will reach 380 million within 20 years. The World Diabetes Day Resolution urges governments to implement national policies for the prevention, care and treatment of diabetes in line with the sustainable development of their healthcare systems. This is the first time that a non-communicable disease has been recognized as posing as serious a global health threat as infectious epidemics like malaria, tuberculosis and HIV/AIDS.

To mark the importance of World Diabetes Day, individuals are encouraged to wear the diabetes pin, which incorporates the blue circle - the global symbol for diabetes. Further details of the campaign and how people can show their support can be found at http://www.worlddiabetesday.org/.

ENDS

Note to Editors
The International Diabetes Federation (IDF) is an umbrella organization of over 200 member associations in more than 160 countries, representing almost 250 million people with diabetes, their families, and their healthcare providers. The mission of the IDF is to promote diabetes care, prevention and a cure worldwide. Its main activities include education for people with diabetes and healthcare professionals, public awareness campaigns and the promotion and exchange of information. IDF is a non-governmental organization in official relations with WHO and associated to the United Nations' Department of Public Information. For more information, please visit www.idf.org.

Introduced by IDF and the World Health Organization in 1991, World Diabetes Day has been celebrated by diabetes representative organizations worldwide ever since. The date of 14 November was chosen because it marks the birthday of Frederick Banting, who, along with Charles Best, is credited with the discovery of insulin. UN Resolution 61/225 establishes November 14 as a United Nations observed day from 2007. Visit www.worlddiabetesday.org for further information about the campaign and for a full list of landmarks that will light up.

-----------------------

MEDIA CONTACTS:
Kerrita McClaughlyn, IDF, +32-487530625 or +1 203 962 1222, media@idf.org
Phil Riley, IDF, +32-495 204964Broadcast videos are available at: http://www.thenewsmarket.com/wdd Download Press Release (PDF) - EN - FR - ES

2007-11-02T17:17:00.000-07:00

Excess body fat, red and processed meats, alcohol raise cancer risk

by Sheryl Ubelacker,
Health Reporter, Canadian Press
Oct. 31, 2007

WASHINGTON - Many kinds of cancer could be prevented with simple lifestyle choices, says a comprehensive new report, which recommends keeping a lean body weight, limiting red meat consumption and ditching processed foods like bacon, hot dogs and luncheon meats except for the odd special occasion.

The 517-page report, released Wednesday by the American Institute for Cancer Research and the World Cancer Research Fund, says there is also convincing evidence linking consumption of alcohol to elevated cancer risk.

But the report by the groups' expert panel - its second in 10 years - aimed its prevention guns at excess body fat as a prime contributor to numerous forms of malignancies, including cancer of the esophagus, pancreas, colon, kidney and uterus, as well as breast cancer in post-menopausal women.

U.K. expert panel member Dr. Philip James told a Washington news conference that reducing average weight on a population basis could slash the number of new cancers worldwide by a third.

"And it's not just a question of simply being fat," he said in a message to individuals. "The evidence that has accumulated is that it's best to be as lean as possible."

James, who established the International Obesity Task Force, said people should aim to be near the bottom of the range that constitutes a healthy body mass index, or BMI.

Regular physical activity - which could be as simple as working up to an hour of brisk walking each day - can help take off pounds as well as cut the risk of several cancers in and of itself, he said.

Dr. Walter Willett, a professor of medicine at the Harvard School of Public Health, said obesity is nipping at the heels of cigarette smoking as the leading cause of preventable cancer.

"We are making progress and need to maintain reduced smoking," Willett said. "Now overweight and obesity are going up. So it will not be too far in the future that overweight and obesity will become the Number 1 cause of cancer."

The report also called on consumers to trim red meats like beef, pork and lamb from their diets to prevent colorectal cancer, saying that intake should be limited to about 500 grams of cooked meat per week. That's the equivalent of six 85-gram portions, each about the size of a deck of cards.

Scientific evidence suggests that every 48 grams of red meat consumed each day beyond the 500-gram weekly allotment increases cancer risk by 15 per cent, compared to someone eating no extra beef, pork or lamb.

But the panel was even more pointed in its recommendations about processed foods as culprits in increased cancer risk. Evidence shows "there is no safe level of consumption" for smoked, cured or salted products such as bacon, ham, sausage and luncheon meats.

"That's why we recommend that if people eat processed meat at all, they save it for special occasions like ham at Christmas or the occasional hot dog at a baseball game," James said.

The meat-limiting message brought a swift reaction from producers.

Lisa Mina, a spokeswoman for Canada's Beef Information Centre, said studies have shown that beef has 14 nutrients essential to good health and is part of Canada's Revised Guide to Healthy Eating. She said Canadians on average already eat less than the amount recommended by the expert panel.

"There is no convincing scientific evidence that consuming red meat, as part of a healthy balanced diet, increases the risk of cancer," the Beef Information Centre, Canadian Pork Council and the Canadian Meat Council said in a joint release. "Cancer is a complex disease with many contributing factors, including physical activity, obesity, smoking, alcohol consumption, diet, as well as family history and age."

The American Meat Institute (AMI) echoed that view, calling the report's conclusions "extreme and unfounded."

"Processed meats that contain nitrate (a preservative) are safe and sodium nitrate is an essential ingredient whose safety is without question," Randy Huffman, AMI Foundation vice-president of scientific affairs, said in a statement.

But the Canadian Cancer Society lauded the report's findings and recommendations.

"What this report is telling us today is that the evidence is more and more convincing about how we live, what we eat and our individual risk of cancer, that there is a role for individuals to reduce their risk of cancer," said Heather Logan, the society's director of cancer control policy.

"Certainly our perspective in looking at the key recommendations from this report is that less is more."

The expert panel also found convincing evidence that alcohol consumption is linked to cancer of the mouth, pharynx, larynx and esophagus, and is implicated in colorectal cancer among men and the probable cause of liver cancer and colorectal cancer in women.

"It doesn't matter whether you are talking about wine, beer or spirits, when it comes to cancer, even small amounts of alcohol raise your risk," James said. "In light of evidence suggesting that small amounts of alcohol protect against heart disease, however, the panel decided to recommend limiting rather than avoiding consumption."

The report advises keeping consumption to no more than two drinks a day for men and one drink daily for women.

The report, entitled Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, is the most comprehensive ever published on the evidence linking cancer risk to diet, physical activity and weight. It is the culmination of a five-year process that involved nine independent teams of scientists from around the world, hundreds of peer reviewers and 21 international experts who reviewed and analyzed more than 7,000 large-scale studies.

-
On the Net:
http://www.dietandcancerreport.org/

-
Here are the key recommendations by the expert panel for preventing cancer:
-Be as lean as possible within the normal range of body weight.
-Be physically active as part of everyday life.
-Limit consumption of energy-dense foods high in fat and sugar but low in fibre. Avoid sugary drinks.
-Eat mostly foods of plant origin.
-Limit intake of red meat and avoid processed meat.
-Limit alcoholic drinks.
-Limit consumption of salt.
-Aim to meet nutritional needs through diet alone.
-Mothers to breastfeed; children to be breastfed.
-Cancer survivors to follow the recommendations for cancer prevention.
"And always remember - do not smoke or chew tobacco."

2007-09-05T08:09:00.000-07:00

The Newest Revolution in Diabetes Treatment: Continuous Glucose Sensing

Posted 08/27/2007
by Anne Peters, MD

Imagine standing on a ledge with your eyes closed, not knowing if your next step forward is to go plummeting downwards or continue climbing up a wall. That is what it is like to have insulin-requiring diabetes and monitor your blood sugar levels just 4 times per day. Insulin is one of the most powerful medications we use, yet is subject to more variation in response than almost any other treatment. Inject too much, exercise more than usual, or eat too little and blood sugar levels can fall fast and hard, at times to the point of a loss of consciousness. Too much carbohydrate causes glucose levels to skyrocket back up.

Any patient taking insulin will tell you that it is tough being a surrogate pancreas. An emerging technology called continuous glucose monitoring is making life a little easier.[1] Patients insert a small sensor under the skin which beams an infrared signal to a receiver where the blood sugar levels are displayed. The pager-like receiver reveals what the blood sugar level is and in which direction it is going. A "normal" blood glucose level of 100 mg/dL that is rising quickly requires a different action than a blood glucose level of 100 mg/dL that is falling quickly.[2] More importantly, these devices alarm at night, alerting patients to potential hypoglycemic reactions. However, all advances come with a price, which includes taking the time to learn and understand this device.

Continuous glucose monitoring suddenly provides up to 1440 daily blood glucose values and it might not reduce A1C levels, because both rates of highs and lows are reduced, leaving the average blood sugar the same. But this technology is worth the price of learning. It is new, imperfect, and somewhat cumbersome,[3,4] yet it stands to help patients with diabetes lead less precarious lives. And ultimately it may evolve into a true "closed loop" system that will make the guesswork of insulin administration a thing of the past.

That's my opinion.

I'm Dr. Anne Peters, Professor of Medicine at the University of Southern California, Keck School of Medicine.

2007-09-05T08:05:00.000-07:00

Rosiglitazone Wrangling Continues in NEJM Correspondence

from Heartwire

by Shelley Wood

(Shelley Wood is a journalist for Medscape. She joined theheart.org, part of the WebMD Professional Network, in 2000 and specializes in interventional cardiology. She studied literature at McGill University and the University of Cape Town and received her graduate degree in journalism from the University of British Columbia, specializing in health reporting. She can be reached at SMWood@webmd.net.)

August 29, 2007 (Boston, MA) - Reaffirming its title as the most hotly disputed drug of the year, rosiglitazone was once again the focus of debate--this time in correspondence appearing in this week's print issue of the New England Journal of Medicine and in additional letters released early online the same day [1,2,3,4,5,6,7,8,9]. Most of the print issue letters quibble with the statistical methods used in Nissen and Wolski's original meta-analysis [10]--to which the authors respond--while the online letters trade barbs over a subsequent rosiglitazone Perspective [11].

In the print issue, Dr Michael B Bracken (Yale University, New Haven, CT); Drs Edoardo Mannucci, Matteo Monami, and Niccolò Marchionni (University of Florence, Italy); and Drs George Diamond and Sanjay Kaul (Cedars-Sinai Medical Center, Los Angeles, CA) all present criticisms of the methods used in the original meta-analysis and offer their own reanalyses to show that the ones chosen by Nissen and Wolski overestimate the degree of risk associated with rosiglitazone. In response, Nissen and Wolski write that they chose the Peto method for their meta-analysis because "it is widely viewed as the optimal approach" for the type of data they were analyzing. They also argue that they did not include other statistical methods in their analysis because they believed the issue needed to be approached "with the same rigor as that used in a randomized trial" and as such prospectively chose a single method and did not apply others in a post hoc manner. They also defend their inclusion of the DREAM and ADOPT trials and reject the Bayesian approach used by Diamond and Kaul as "controversial."

Yet another letter, this one by Dr Alan S Brett (University of South Carolina, Columbia), takes issue with points made in the Psaty and Furberg editorial that originally accompanied the Nissen-Wolski meta-analysis [12]. Psaty and Furberg, writes Brett, "disparage physicians who have prescribed rosiglitazone" because of its effect on glycemic control. "It is unreasonable to expect that practicing physicians would be more knowledgeable about fine distinctions between outcomes and surrogate end points than are the experts who guide clinical practice," Brett notes. In response, Psaty and Furberg counter that the rapid uptake of rosiglitazone happened in the absence of a trial examining hard events and that physicians chose rosiglitazone over other available antidiabetic drugs despite not having hard data showing health benefits of glucose-lowering. "Treatment decisions based on surrogate end points should be made with caution," they insist.

Debating FDA reform

This week's print issue also contains the Perspective by Dr Clifford J Rosen (St Joseph Hospital, Bangor, ME), published online August 8, 2007, as previously reported by heartwire. It, too, produced a minor squall of letters released online today. In one, FDA officials, led by Dr Hyton V Joffe, defend the use of surrogate end points in the approval of diabetes drugs but concede that postapproval studies looking at cardiovascular outcomes might be a "reasonable approach." A second letter, this one from rosiglitazone manufacturer GlaxoSmithKline (GSK), suggests that Rosen's Perspective "leaves readers with a misconception" about the FDA advisory committee's advice to the FDA. In his letter, senior VP of worldwide development, Dr Ronald Krall, clarifies that the advisory committee drew a distinction between rosiglitazone's MI risk as compared with placebo and as compared with other antidiabetic drugs, with the major signal of risk being seen when a placebo comparator was used. Rosen, in a third letter, replies that his primary intention had been to provide "an individual account of an extraordinary FDA advisory committee meeting."

But Rosen reiterates his views about important improvements he believes are needed to the FDA approval and oversight, insisting that the process of reporting adverse events needs an overhaul, including the creation of a "totally independent" data and safety monitoring board within the FDA.

References

1. Bracken MB. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:937-938.
2. Mannucci E, Monami M, Marchionni N. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:938li>
3. Diamond GA, Kaul S. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:938-939.
4. Brett AS. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:939.
5. Nissen SE, Wolski K. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:939-940.
6. Psaty BM, Furberg CD. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 357:940.
7. Joffe HV, Parks MH, Meyer RJ, et al. Rosiglitazone and the FDA. N Engl J Med 2007; DOI: 10.1056/NEJMc076347. Available at: http://www.nejm.org.
8. Krall RL. Rosiglitazone and the FDA. N Engl J Med 2007; DOI: 10.1056/NEJMc076347. Available at: http://www.nejm.org.
9. Rosen CJ. Rosiglitazone and the FDA. N Engl J Med 2007; DOI: 10.1056/NEJMc076347. Available at: http://www.nejm.org.
10. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular disease. N Engl J Med 2007; 356:2457-2471. Abstract
11. Rosen C. The rosiglitazone story. Lessons from an FDA advisory committee meeting. N Engl J Med 2007; 357: 844-846. Abstract
12. Psaty B and Furberg C. Rosiglitazone and cardiovascular risk. N Engl J Med 2007; 356:2522-2524. Abstract

The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

2007-09-05T07:57:00.000-07:00

Treating the Whole Patient for Optimal Management of Type 2 Diabetes

Considerations for Insulin Therapy

Carlos Campos, MD, MPH

South Med J. 2007;100(8):804-811.
Posted 08/28/2007

Abstract and Introduction

Abstract
Primary care physicians are responsible for providing healthcare to most patients with type 2 diabetes. In this role, it is critical that physicians utilize a whole-patient treatment approach that includes lifestyle modifications and pharmacotherapy aimed to achieve glycemic control, in addition to the management of any comorbid conditions or risk factors for cardiovascular complications of diabetes. Due to the progressive nature of the disease, most patients with type 2 diabetes will eventually require insulin to achieve and maintain glycemic control, because of both increased insulin resistance and diminished secretory capacity of the pancreatic ß cells. Thus, physicians need to be knowledgeable about and comfortable with the use of insulin, as well as with educating patients and discussing any potential barriers to insulin therapy. The use of a stepwise approach-beginning with basal insulin therapy and adding prandial insulin if necessary-is simple, effective, and appropriate for use in many patients.

Introduction
In the United States, the incidence of diabetes has increased substantially over the past few years, reaching nearly 21 million in 2005, and is expected to continue to grow.[1] Of note, the occurrence of diabetes varies by ethnicity, with African Americans, Hispanic and Latino Americans, Native Americans, and Alaska Natives being 1.7 to 2.2 times more likely to have diabetes than non-Hispanic whites.[1] Diabetes frequency also varies by age.[1,2]

Several factors have contributed to the rising prevalence of diabetes seen in the United States, including the aging of the population, increasing rates of obesity in the general population, and the shift to more sedentary lifestyles.[3] The pervasiveness of diabetes among children and adolescents is also recognized as a serious health problem.[4] The total healthcare costs for diabetes were estimated at $132 billion in the United States in 2002, with direct medical costs of approximately $92 billion.[1] It is clear that diabetes represents a serious and costly public health issue that has reached epidemic proportions.

Type 2 diabetes is a progressive disease, characterized by both insulin resistance and the gradual decline of insulin secretion. Prediabetes-defined as the presence of impaired glucose tolerance or impaired fasting glucose or both-often leads to the development of type 2 diabetes and increases the risk of heart disease and stroke.[1] Although insulin resistance (a condition where the body does not respond to or utilize insulin appropriately) remains relatively stable throughout the course of type 2 diabetes, the pancreatic ß cells gradually lose the ability to secrete enough insulin to overcome the hyperglycemia caused by insulin resistance. As the degree of ß-cell function progressively worsens, patients eventually become insulin deficient and often suffer from the complications associated with chronic hyperglycemia, including heart disease, kidney disease, and stroke.

Primary care physicians play a major role in the care of patients with diabetes, providing diabetes care to 39% of patients with type 1 diabetes and 82% of those with type 2 diabetes.[5] These physicians face multiple challenges in providing comprehensive treatment, and the focus has shifted from merely managing the patient's diabetes to actively addressing other coexisting conditions (such as hypertension, dyslipidemia, and obesity) within the context of diabetes management. Finally, individual factors and potential barriers to treatment must also be taken into consideration when selecting an appropriate treatment regimen.

Management of Type 2 Diabetes: More Than Just Glycemic Control
The treatment of diabetes has traditionally focused on glycemic control. Furthermore, recent clinical studies have provided strong evidence that optimal disease management should include strategies that address traditional cardiovascular (or cardiometabolic) risk factors commonly seen in patients with type 2 diabetes. These risk factors include hypertension, dyslipidemia, lack of physical activity, smoking, and poor dietary habits, which promote the development of insulin resistance and heart disease.[6] An intensive, integrated approach that addresses multiple components of cardiometabolic risk is warranted considering the serious impact of diabetes on cardiovascular outcomes. Epidemiologic studies have documented a much higher prevalence of coronary heart disease in people with diabetes (approximately 45%), compared with people without diabetes (approximately 23%).[7] Furthermore, cardiovascular disease has been estimated to account for approximately 65% of all deaths in patients with diabetes.[1] Table 1 summarizes currently recommended goals for the treatment of hypertension and dyslipidemia in patients with diabetes, with the goal of reducing cardiovascular risk.

With regard to glycemic control, comprehensive consensus guidelines for the management of type 2 diabetes have been issued by the American Diabetes Association (ADA) and the American College of Endocrinology (ACE). The primary goals of treatment are to achieve normoglycemia and prevent the development of the microvascular and macrovascular complications associated with type 2 diabetes. Some clinicians advocate for a more individualized approach, aimed toward reducing A1c concentrations as low as possible without causing unacceptable hypoglycemia in older patients and reserving intensive therapy for younger patients.[5]

Unfortunately, recent surveys indicate that a large proportion of patients with diabetes fail to meet any of these recommended glycemic goals, despite numerous advances in treatment. In one survey conducted by the American Association of Clinical Endocrinologists (AACE), data were collected from more than 157,000 people with type 2 diabetes over a 2-year period (2003-2004) and measured against the AACE A1c goal of ≤6.5%.[8] Two out of 3 patients (67%) failed to meet that goal.[8] These findings are consistent with those of earlier cross-sectional surveys such as the Third National Health and Nutrition Examination Survey (NHANES III, conducted 1988-1994) and NHANES 1999 to 2000, which revealed that 56 to 63% of patients with diabetes failed to achieve the ADA recommended target A1c of <7.0%.[9] Furthermore, the overall percentage of patients who achieved currently recommended goals for the treatment of hypertension and hyperlipidemia in connection with the target A1c level was only 7.3% in NHANES 1999 to 2000, and a slightly lower percentage (5.2%) achieved all 3 goals simultaneously in NHANES III.[9] Clearly, improved strategies that address all of the pathophysiologic mechanisms of diabetes-beyond glycemic control-are urgently needed for the optimal management of diabetes.

Disease Monitoring and Treatment Response
The optimal management of diabetes requires vigilant tailoring of therapy to the requirements of the patient. Blood glucose concentrations can be measured directly (ie, fasting and postprandial glucose measurements) to assess glycemic control at any given point in time. Glycemic control is also assessed by measuring A1c concentrations, which result from the nonenzymatic glycosylation of the ß chain of hemoglobin with plasma glucose. A1c concentrations increase in proportion to plasma glucose levels and indicate the extent of a patient's overall glycemic control over the preceding 2- to 3-month period.[10]

The relationship between A1c and the incidence of diabetic complications in patients with type 2 diabetes has been explored in the United Kingdom Prospective Diabetes Study (UKPDS). This study compared the effects of conventional (dietary modification) and intensive (sulfonylurea or insulin) therapy on glycemic control and the risk of complications in patients with newly diagnosed type 2 diabetes.[11] Median A1c values were 7.0% in the intensive diabetes treatment group-an 11% reduction during the 10-year treatment period relative to the conventional treatment group. The reduction in A1c seen with intensive treatment was associated with improved morbidity and mortality, with the risk of any diabetes-related endpoint (ie, sudden death, death from hyperglycemia or hypoglycemia, myocardial infarction, angina, heart failure, stroke, renal failure, amputation, retinopathy, blindness, or cataract surgery) 12% lower in the intensive therapy group compared with the conventional therapy group (P = 0.029). Similarly, the risk of diabetes-related death was reduced by 10% and all-cause mortality was reduced by 6% in patients receiving intensive therapy.[11]

Ethnicity and Diabetes Complications
Ethnicity also appears to play a role in the risk of the development of long-term complications of diabetes. African Americans experience higher rates of cardiovascular disease, blindness, amputation, and end-stage renal disease than are seen in the general population of patients with diabetes.[2] Evidence from NHANES III also suggests that Mexican Americans are at higher risk of retinopathy than non-Hispanic blacks and non-Hispanic whites.[12] However, the increased rates of complications may reflect the level of glycemic control achieved; thus, it is expected that improved glycemic control would reduce the development of complications in these ethnic populations.

Results from two key studies suggest that if hyperglycemia and other risk factors are addressed appropriately, the rates of complications may actually be comparable among ethnic groups. The San Luis Valley study examined the prevalence of diabetes complications (namely, neuropathy, retinopathy, and nephropathy) in both Hispanic and non-Hispanic white patients in southern Colorado.[13,14] The investigators found that the prevalence of neuropathy and nephropathy were comparable and that the duration-adjusted prevalence of retinopathy was actually higher in non-Hispanic white patients than in Hispanics.[14] Of note, there were no significant differences between ethnic groups in terms of the duration of diabetes and A1c concentrations. The second study compared the incidence of diabetic complications in Jamaicans, West Indian blacks, and whites in Britain.[15] After adjusting for between-group differences in the duration of diabetes, no significant differences were noted in the incidence of background retinopathy or other complication rates, even though whites had significantly lower A1c concentrations than either West Indian blacks or Jamaicans.[15] Taken together, these results may imply that when all diabetes-related factors are equal (ie, blood glucose and other risk factors are controlled) the rate of diabetic complications in high-risk ethnic groups is comparable to that of non-Hispanic whites, further emphasizing the importance of optimal glycemic control in reducing the risk of complications in patients with type 2 diabetes.

Traditionally, the management of diabetes includes dietary modifications and exercise, either alone or in combination with pharmacologic therapy. In addition to the need to achieve good glycemic control, the presence of other comorbid conditions must be evaluated and managed with appropriate interventions. Obesity, high blood pressure, and dyslipidemia are all risk factors for cardiac disease and may necessitate earlier initiation of insulin therapy in addition to aggressive lifestyle modifications and pharmacologic treatment of the conditions themselves. Such interventions can reduce the risk of diabetes-related cardiovascular complications by approximately 20 to 50%.[1]

Throughout the course of treatment, glycemic control should be evaluated using a combination of A1c testing and results from patient self-monitoring of blood glucose ( Table 1 ).[10] A1c concentrations should be measured at 3-month intervals to determine whether glycemic targets are being met. Fasting plasma glucose and postprandial plasma glucose results obtained by self-monitoring both contribute to overall glycemic control and can help guide treatment dose adjustments.[16,17] By reviewing all of these endpoints with patients, physicians can identify patterns of glycemic control and easily identify a need for intensification of treatment.

When sufficient efforts with diet and exercise fail to achieve glycemic control, pharmacologic treatment is indicated. As shown in Figure 1, the next steps in diabetes management usually involve treatment with 1 or more oral antidiabetic drugs (OAD).[18] Currently, there are 6 classes of oral agents available: sulfonylureas, meglitinides, biguanides, α-glucosidase inhibitors, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors. Review of the literature indicates that each class reduces A1c by 1.0% to 2.0%; because each class has its own distinct mechanism of action, combined treatment approaches are frequently used, with potential additive effects on glycemic control.[19,20] A detailed review of OAD therapy is beyond the scope of this review; however, those wishing more information are directed to reviews by Inzucchi[19] and Willett and Albright.[21]

Figure 1.
Stepwise approach to glycemic control in patients with type 2 diabetes. Goals. d• FPG <100 mg/dL.• 2-hour PPG <140 mg/dL.• A1c as low as possible without serious hypoglycemia.A1c, glycosylated hemoglobin; AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association; FPG, fasting plasma glucose; PPG, postprandial plasma glucose.a Oral agent may be started simultaneously with diet and exercise.b May require 6 months to see maximal effect of a thiazolidinedione.c Insulin may be used earlier and as initial therapy in some patients, such as those who are pregnant, hospitalized, or very symptomatic.d May start 2 oral agents together (eg, if high baseline A1c).e Exenatide has recently become available and may be a consideration.[27]f AACE recommends an A1c level ≤6.5%, FPG level ≤110 mg/dL, and PPG level ≤140 mg/dL; ADA recommends an A1c level <7.0%, FPG level 90 to 130 mg/dL, and PPG (1-2 h) level <180 mg/dL.Adapted with permission from Dailey G. A timely transition to insulin: identifying type 2 diabetes patients failing oral therapy. Formulary 2005;40:114-130.

Although treatment with OADs is effective when used alone or in combination, the progressive decline in pancreatic ß-cell function seen in patients with type 2 diabetes will eventually result in the need for insulin therapy to achieve or maintain adequate glycemic control.[22-24] Results from the UKPDS have shown that one half of the patients receiving sulfonylurea treatment were able to maintain A1c <7.0% after 3 years of treatment. As time went on, fewer patients were able to achieve glycemic control with sulfonylurea therapy alone, with 34% of patients having A1c levels <7.0% after 6 years of treatment.[22] After 9 years of treatment, only 24% of patients were able to achieve adequate glycemic control with sulfonylurea treatment.[22] Notably, treatment with other OADs was associated with a similar progressive decline in glycemic control over time.[22] Because treatment failure may occur over a short period of time, regular patient monitoring at 3-month intervals is recommended in patients who are not achieving glycemic goals as measured by self-monitoring of blood glucose.[10]

When Is the Initiation of Insulin or Intensification of the Existing Insulin Regimen Appropriate?
Treatment options for patients who are already receiving maximum doses of 2 OADs involve either adding a third OAD (such as a thiazolidinedione) to the current regimen or the initiation of insulin to achieve glycemic control; no longer than 3 months (6 mo if a thiazolidinedione is added) should be allowed to elapse without intensifying treatment for patients who are not achieving glycemic targets (Figure 1).[16,18,25] Generally, physicians should consider starting basal insulin therapy in patients whose A1c level is >7.0% (>6.5% if following ACE guidelines) despite optimal oral therapy.

The goals of insulin therapy involve the administration of exogenous insulin to approximate the normal physiologic patterns of pancreatic insulin secretion and reduce A1c, fasting, and postprandial plasma glucose concentrations to recommended target levels. Thus, physiologic insulin regimens attempt to mimic normal insulin secretion in healthy individuals by addressing basal and prandial needs separately. From a clinical perspective, basal insulin replacement mimics the constant physiologic release of insulin that regulates metabolism and hepatic glucose production.[26] Prandial insulin replacement is intended to mimic the postmeal insulin response to nutrient intake. Another injectable agent that may be considered for postprandial glucose control, the incretin mimetic exenatide, is administered before morning and evening meals but is not yet approved for use with insulin.[27] Finally, correction-dose insulin is given to control pre- or between-meal hyperglycemia.[26] Thus, the selection of insulin therapy is based on pharmacokinetic properties ( Table 2 ), with longer-acting insulins used for basal therapy and rapid-acting insulins used prandially. Several premixed insulin preparations are also available and are aimed toward simplifying insulin regimens with twice-daily dosing. However, these preparations have limited flexibility, which may be an issue for a patient whose insulin deficiency is severe, as there may not be sufficient insulin available to meet postlunch requirements.[26] Thus, mixed insulins may be most appropriate for patients who eat relatively small lunches or are unable to adhere to more complex insulin regimens.[26] Importantly, due to the progressive loss in the insulin secretory capacity of pancreatic ß cells, type 2 diabetes, there is a need for exogenous insulin therapy.

Basal Insulin Therapy
Perhaps the most simple and effective approach toward intensifying therapy is to add basal insulin to the existing OAD regimen. This approach improves glycemic control and decreases the risk of diabetic complications by first reducing fasting plasma glucose concentrations, which in turn results in lower postprandial plasma glucose concentrations.[28] Intermediate-acting insulin, such as neutral protamine Hagedorn (NPH), and long-acting insulin analogs such as insulin glargine and insulin detemir, provide therapeutic options for basal insulin replacement ( Table 2 ).[5] Insulin glargine has a relatively consistent time-action profile, is effective for use as a once-daily injection, and offers greater dosing flexibility, as it may be administered either at bedtime or in the morning.[29-31] Insulin detemir was approved recently for once- or twice-daily dosing.

A 22-week comparison between once- or twice-daily insulin detemir plus a rapid-acting analog versus NPH plus regular human insulin was conducted in patients with type 2 diabetes.[32] The A1c reduction was comparable with a lower but not statistically different rate of hypoglycemia in patients receiving insulin detemir; the majority of patients required twice-daily dosing in both treatment groups. Several clinical studies have compared once-daily insulin glargine with once- or twice-daily NPH insulin when added to OAD therapy in patients with type 2 diabetes.[30,31,33-35] In each of these studies, the addition of insulin glargine or NPH insulin to oral therapy improved glycemic control from baseline levels, with 2 studies indicating better glycemic control with insulin glargine.[30,34] With regard to safety, insulin glargine has demonstrated a consistent advantage over NPH insulin in terms of significantly fewer episodes of nocturnal hypoglycemia.[30,31,33,35,36] This is an important difference, as concerns about the risk of hypoglycemia may be a common barrier to the initiation of insulin for both physicians and patients.[37]

Prandial Insulin Therapy
Although both the fasting plasma glucose and postprandial plasma glucose contribute to A1c, the relative contribution of prandial glucose excursions to A1c is greater at lower A1c levels.[38] Thus, patients may need the addition of prandial insulin to basal insulin therapy if they are nearing target fasting plasma glucose concentrations but their A1c level is >7.0% and/or postmeal blood glucose concentrations remain above target levels. Available options for initiating prandial insulin therapy include regular human insulin, rapid-acting insulin analogs (insulin aspart, insulin lispro,[5,39] insulin glulisine) and inhaled insulin. The rapid-acting insulin analogs are particularly well-suited for prandial glycemic control, with peak concentrations occurring within 1 hour of administration and antihyperglycemic effects lasting for 5 hours, which closely mimics normal physiology ( Table 2 ).[5] Inhaled insulin similarly has a rapid onset and peak and offers a noninjectable option. Regular human insulin has a delayed absorption and prolonged duration of action, making it less desirable because it must be given 30 to 45 minutes before a meal. However, although the addition of prandial insulin to basal insulin is an effective approach to physiologic insulin replacement, some patients may be resistant to multiple daily injections.[18]

An effective strategy for introducing prandial insulin is to add it gradually, starting with administration before the largest meal of the day, with the goal of improving glycemic control in patients already receiving basal insulin therapy. As the disease progresses, prandial insulin can be added to additional meals if required to maintain glycemic control.
Premixed Insulins
As mentioned previously, premixed insulins have been developed in an effort to address basal and prandial insulin requirements with fewer injections, but these products require rigid adherence to regular mealtimes and limit the ability to adjust the dosages of the individual components.

Potential Barriers to Insulin Therapy
Despite the many clinical benefits of insulin therapy for patients with type 2 diabetes, many patients and physicians are reluctant to begin insulin treatment, even if it is clearly indicated to achieve optimal glycemic control. There are many potential reasons for this reluctance. Physicians may be concerned about the possible side effects (ie, weight gain, hypoglycemia), as well as having limited time for patient education regarding proper insulin administration techniques.[18] In addition to the anxiety about potential side effects and learning self-injection techniques, patients may be concerned about the possibility of discomfort related to injections and complexity of regimens. Finally, some patients have the misperception that the need to start insulin therapy is a signal that their diabetes has advanced to a more serious stage or that they have failed in their efforts to achieve glycemic control.[40]

Physicians can help their patients by taking an active role in addressing or eliminating some of these barriers to treatment. Patients should be informed that hypoglycemia can be expected with the initiation of insulin therapy but that severe hypoglycemia is rare in patients with type 2 diabetes, affecting less than 1% of patients receiving insulin.[37] Education about proper self-monitoring of blood glucose, in conjunction with discussions of how to avoid, recognize, and treat the symptoms of hypoglycemia, may also be helpful in addressing the fear of hypoglycemia as a barrier to treatment. In addition, group diabetes patient education programs have been shown to improve glycemic control and quality of life in patients with type 2 diabetes, as well as the ability of such patients to self-manage their insulin therapies.[41]

It is important to explore the potential barriers to treatment with each patient and enlist family members to help encourage the patient to accept and adhere to the insulin regimen. For example, a patient may be a candidate for insulin therapy but has a language barrier that further complicates the initiation of insulin. The use of Spanish-speaking healthcare staff in offices serving large Hispanic populations would facilitate patient education. Notably, the ADA offers a Spanish-language website with patient education information and resources (www.portufamilia.org).[42] A recent study observed that culturally appropriate health education has a high potential to positively impact the health of Hispanic migrant farmworkers.[43]

Addressing Socioeconomic Barriers to Care: A Nonprofit Model
It is difficult to care for the whole patient and not address his or her socioeconomic situation. Healthcare professionals and community groups should partner to address such issues. For example, I founded a nonprofit organization, The Institute for Public Health and Education Research Inc., (TIPHER),[44] to help address community healthcare issues. We collaborated with other foundations, as well as private and public organizations, to build and manage a community center in the most indigent section of our service area. Free diabetes education classes are provided at this center that address patient health management. In addition, high-school diploma equivalency (GED) and English as a second language (ESL) classes are provided to improve the patient's ability to obtain better employment and thus gain access to healthcare (health insurance). A medical ESL class is also offered to increase the patient's ability to understand healthcare providers and thus facilitate healthcare for themselves and their families. This class teaches medical terminology, which can prepare students to take a certified nurse assistant class and can open employment opportunities in the healthcare industry. Additional community support services include after-school tutoring for children at risk for dropping out of school and a volunteer-run soup kitchen that serves a noon meal Monday through Friday. My experience with this center illustrates that primary care physicians can facilitate more than prevention of end-organ damage when addressing the whole patient. We truly need to be advocates for our patients. Addressing barriers that affect access to healthcare is imperative.

Conclusions
Primary care physicians are responsible for providing healthcare to most patients with type 2 diabetes. In this role, it is critical that physicians utilize a whole-patient approach that includes lifestyle modifications and pharmacologic therapy designed to achieve glycemic control, as well as management of any other comorbid conditions and risk factors for the cardiovascular complications of diabetes.

Although many patients initially will achieve adequate glycemic control with OADs, the progressive nature of type 2 diabetes results in the eventual need for the addition of insulin; indeed, the addition of insulin therapy is the key to glycemic control in many patients. Thus, physicians need to be comfortable with the use of insulin, as well as with educating patients and discussing any potential barriers to insulin therapy. The use of a stepwise approach-beginning with the initiation of basal insulin therapy and adding prandial insulin if necessary-is simple, effective, and appropriate for many patients. By individualizing care and taking the patient's specific needs and concerns into consideration, physicians can successfully manage diabetes and prevent the development of long-term complications.

References:

1. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2005.
2. American Diabetes Association. Diabetes statistics for African Americans. Available at: http://www.diabetes.org/diabetes-statistics/african-american.jsp . Accessed April 8, 2007.
3. Skyler JS, Oddo C. Diabetes trends in the USA. Diabetes Metab Res Rev 2002;18(suppl 3):S21-S26.
4. Pinhas-Hamiel O, Zeitler P. The global spread of type 2 diabetes mellitus in children and adolescents. J Pediatr 2005;146:693-700.
5. DeWitt DE, Hirsch IB. Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review. JAMA 2003;289:2254-2264.
6. Gæde P, Pedersen O. Multi-targeted and aggressive treatment of patients with type 2 diabetes at high risk: what are we waiting for? Horm Metab Res 2005;37(suppl 1):76-82.
7. Wingard DL, Barrett-Connor E. Heart disease and diabetes. In: Harris MI, Cowie CC, Stern MP, Boyko EJ, Reiber GE, Bennett PH, et al (eds). Diabetes in America. 2nd ed. Washington, DC, National Institutes of Health, 1995: pp. 429-448.
8. American Association of Clinical Endocrinologists. State of diabetes in America [press release] Available at: http://www.aace.com/newsroom/press/2005/index.php?r=20050510 . Accessed April 8, 2007.
9. Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 2004;291:335-342.
10. American Diabetes Association. Standards of medical care in diabetes: 2006. Diabetes Care 2006;29(suppl 1):S4-S42.
11. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853.
12. Harris MI, Klein R, Cowie CC, et al. Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A US population study. Diabetes Care 1998;21:1230-1235.
13. Hamman RF, Marshall JA, Baxter J, et al. Methods and prevalence of non-insulin-dependent diabetes mellitus in a biethnic Colorado population: the San Luis Valley Diabetes Study. Am J Epidemiol 1989;129:295-311.
14. Hamman RF, Franklin GA, Mayer EJ, et al. Microvascular complications of NIDDM in Hispanics and non-Hispanic whites: San Luis Valley Diabetes Study. Diabetes Care 1991;14:655-664.
15. Cruickshank JK, Alleyne SA. Black West Indian and matched white diabetics in Britain compared with diabetics in Jamaica: body mass, blood pressure, and vascular disease. Diabetes Care 1987;10:170-179.
16. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2005;28(suppl 1):S4-S36.
17. Rohlfing CL, Wiedmeyer H-M, Little RR, et al. Defining the relationship between plasma glucose and HbA1c: analysis of glucose profiles and HbA1c in the Diabetes Control and Complications Trial. Diabetes Care 2002;25:275-278.
18. Dailey G. A timely transition to insulin: identifying type 2 diabetes patients failing oral therapy. Formulary 2005;40:114-130.
19. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360-372.
20. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999;131:281-303.
21. Willett LL, Albright ES. Achieving glycemic control in type 2 diabetes: a practical guide for clinicians on oral hypoglycemics. South Med J 2004;97:1088-1092.
22. Turner RC, Cull CA, Frighi V, et al. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA 1999;281:2005-2012.
23. UK Prospective Diabetes Study Group. UK Prospective Diabetes Study 16: overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 1995;44:1249-1258.
24. Wright A, Burden ACF, Paisey RB, et al. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the UK Prospective Diabetes Study (UKPDS 57). Diabetes Care 2002;25:330-336.
25. Yale J-F, Valiquett TR, Ghazzi MN, et al. The effect of a thiazolidinedione drug, troglitazone, on glycemia in patients with type 2 diabetes mellitus poorly controlled with sulfonylurea and metformin: a multicenter, randomized, double-blind, placebo-controlled trial. Ann Intern Med 2001;134:737-745.
26. Hirsch IB. Insulin analogues. N Engl J Med 2005;352:174-183.
27. Heine RJ, Van Gaal LF, Johns D, et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med 2005;143:559-569.
28. Carroll MF, Izard A, Riboni K, et al. Fasting hyperglycemia predicts the magnitude of postprandial hyperglycemia: implications for diabetes therapy. Diabetes Care 2002;25:1247-1248.
29. Lepore M, Pampanelli S, Fanelli C, et al. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes 2000;49:2142-2148.
30. Fritsche A, Schweitzer MA, Häring HU. Glimepiride combined with morning insulin glargine, bedtime neutral protamine Hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med 2003;138:952-959.
31. Yki-Järvinen H, Dressler A, Ziemen M. HOE 901/3002 Study Group: less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care 2000;23:1130-1136.
32. Rašlova K, Bogoev M, Raz I, et al. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract 2004;66:193-201.
33. Riddle MC, Rosenstock J, Gerich J, et al, on behalf of the Insulin Glargine 4002 Study Investigators. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-3086.
34. Ryysy L, Yki-Järvinen H, Hänninen J. Simplifying treat to target - the LANMET study. In: Program and abstracts of the 40th European Association for the Study of Diabetes Annual Meeting. September 5-9, 2004; Munich, Germany. Abstract 749.
35. Massi Benedetti M, Humburg E, Dressler A, et al. A one-year, randomised, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes. Horm Metab Res 2003;35:189-196.
36. Rosenstock J, Schwartz SL, Clark CM Jr, et al. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001;24:631-636.
37. Miller CD, Phillips LS, Ziemer DC, et al. Hypoglycemia in patients with type 2 diabetes mellitus. Arch Intern Med 2001;161:1653-1659.
38. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA1c. Diabetes Care 2003;26:881-885.
39. Dailey G, Rosenstock J, Moses R, et al. Glycemic control with insulin glulisine versus regular human insulin in a basal-bolus regimen in patients with type 2 diabetes. In: Program and Abstracts of the American Diabetes Association 64th Annual Scientific Sessions. June 4-8, 2004; Orlando, FL.
40. Hunt LM, Valenzuela MA, Pugh JA. NIDDM patients' fears and hopes about insulin therapy: the basis of patient reluctance. Diabetes Care 1997;20:292-298.
41. Meneghini LF, Wick AK, Delamater AM, et al. Group-based self-management intervention for intensification of insulin therapy. In: Program and Abstracts of the American Diabetes Association 63rd Annual Scientific Sessions. June 13-17, 2003; New Orleans, LA. Abstract 131-OR.
42. American Diabetes Association. Por tu familia: la diabetes y los latinos. Available at: http://www.portufamilia.org . Accessed April 8, 2007.
43. Heuer L, Hess CW, Klug MG. Meeting the health care needs of a rural Hispanic migrant population with diabetes. J Rural Health 2004;20:265-270.
44. TIPHER: The Institute for Public Health and Education Research. Available at: http://www.tipher.com/index.htm . Accessed April 8, 2007.
45. American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control. Endocr Pract 2002;8(suppl 1):5-11.
46. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-2572.
47. National Cholesterol Education Program. Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Final Report. Washington, DC: US Department of Health and Human Services, National Institutes of Health. September 2002. NIH Publication No. 02-5215.
48. Levemir [package insert]. Princeton, Novo Nordisk Inc, 2005.
49. Apidra [package insert]. Kansas City, Aventis Pharmaceuticals Inc, 2004.
50. Exubera [package insert]. New York, Pfizer Inc, 2006.

Funding Information
This article was supported by Sanofi-Aventis US.

Reprint Address
Carlos Campos, 189 E Austin, Suite 102A, New Braunfels, TX 78130. Email: camposmdmph@yahoo.com .

Carlos Campos, MD, MPH, Institute for Public Health and Education Research Inc., New Braunfels, TX

Dr. Campos receives grants from the following companies: Eli Lilly and Co; Bristol-Myers Squibb Company; Merck & Co, Inc; Sanofi-Aventis US; Novartis Pharmaceuticals Corporation; Amylin Pharmaceuticals, Inc; AstraZeneca Pharmaceuticals LP; and Forest Pharmaceuticals, Inc.

2007-07-29T17:53:00.000-07:00

Diabetes drugs could double risk of heart failure

Last Updated: Friday, July 27, 2007
CBC News

A class of diabetes drugs may greatly increase a person's chance of heart failure, says a U.S. research review.

The risk of heart failure in patients taking thiazolinediones, can be up to 100 per cent higher than in those who forgo the drugs, researchers at Wake Forest University in North Carolina have found after studying randomized trials, controlled observational studies and case reports.

Thiazolinediones led to heart disease even in patients who had no known cardiac risks, the report finds.
Thiazolinediones, which include medications like Avandia and Actos, are known to enhance insulin sensitivity.
The research findings will appear in the August issue of Diabetes Care.

In the research review, heart failure occurred equally at high and low doses. The medium time for the onset of heart failure was 24 weeks after beginning drug therapy. The median age of victims was 67, with 26 per cent of all cases below age 60.

"The occurrence of heart failure several months after initiation of treatment suggests a long-term effect of the drugs, which may not be avoided by beginning with low doses," said Sonal Singh, lead author of the report, in a release.

Currently, the product label for both drugs cautions patients with severe heart failure about taking the drugs. It also warns about the increased risk of heart failure if used in combination with insulin, a mainstay of diabetes treatment.

But the report finds that heart failure can occur even if patients don't have any heart problems. For that reason, the authors call for a review of the recommendations of both the American Heart Association and the American Diabetic Association. Both groups recommend thiazolinediones to diabetics with early-stage heart failure or one or more risk factors for cardiac problems, without heart disease.

The researchers theorize that the development of heart failure may be caused by fluid retention brought on by the thiazolinediones in people who are susceptible, or in people who have latent heart disease.

On May 31, Health Canada issued an communique about Avandia, regarding its connection to an increased risk of heart attack and cardiovascular death in patients with Type 2 diabetes. Further investigation of these results is underway.

According to the Canadian Diabetes Association, two million Canadians have diabetes. Four out of five people with diabetes will die of heart disease and studies also show that people with diabetes are prone to heart disease at a much earlier age than those without diabetes.

Risk factors include high blood glucose levels, elevated blood pressure, being overweight and having high cholesterol levels.

2007-07-09T16:00:00.000-07:00

Selenium supplements do not prevent diabetes and may actually be harmful, concludes a new study in Annals of Internal Medicine.

Source: http://news.sympatico.msn.ctv.ca/TopStories/ContentPosting.aspx?feedname=CTV-TOPSTORIES_V2&showbyline=True&newsitemid=CTVNews%2f20070709%2fselenium_070709

Researchers reviewed a study that was designed to evaluate whether selenium supplements prevented skin cancer and looked at the effects the supplement had on diabetes incidence.

Among the 1,202 participants who participated in the study, half of the group received a 200-microgram selenium supplement and half received a placebo pill for an average of 7.7 years.

They found that those who took the selenium supplement had an increased risk of developing Type 2 diabetes than those who took a placebo or dummy pill.

They found:
58 out of 600 participants in the selenium group developed type 2 diabetes
only 39 out of 602 participants in the placebo group developed the disease.
By the end of the study, the relative risk rate was approximately 50 per cent higher among those in the selenium group than among those in the placebo group. The risk of developing diabetes tended to be higher in people who had higher blood selenium levels at the start of the study.

Selenium is a naturally occurring trace mineral present in soil and foods. The body needs selenium in minute amounts to aid in metabolism.

Selenium supplements are widely promoted on the Internet for conditions ranging from cold sores and shingles to arthritis and multiple sclerosis. They are sold to prevent aging, enhance fertility, prevent cancer and get rid of toxic minerals such as mercury, lead and cadmium.

Selenium supplements have shown some promise in preventing prostate cancer. Because of selenium's antioxidant activities, some scientists feel it might be effective against diabetes.
Dr. Saverio Stranges, lead author of the study, says it's not clear why selenium would be associated with an increased risk of developing diabetes.

"No single study can provide the answer to a scientific question, but at this time, selenium supplementation does not appear to prevent type 2 diabetes, and it may increase risk of the disease. However, our understanding of the mechanisms whereby selenium would increase risk of diabetes is very limited at this time and this issue needs to be further explored.

"Nevertheless, I would not advise patients to take selenium supplements greater than those in multiple vitamins."

In an accompanying editorial, Dr. Eliseo Guallar from Johns Hopkins University Bloomberg School of Public Health, agrees that selenium seems to offer few benefits and at high levels, may be toxic.

Dr. Guallar says most people have adequate selenium in their diet.

"Moreover, taking selenium supplements on top of an adequate dietary intake may cause diabetes."

2007-06-11T07:36:00.000-07:00

Time Watching Television Linked to Glucose Control in Pediatric Type 1 Diabetes

Source: http://www.medscape.com/viewarticle/557463?src=mp

May 30, 2007 — In children and adolescents with type 1 diabetes, there is a continuous increase in glycated hemoglobin (HbA1c) level with every hour of watching television, according to the results of a population-based study published in the June issue of Diabetes Care.

"Sedentary behavior is associated with increased risk of obesity and cardiovascular disease (CVD) risk factors, and physical inactivity and lack of physical fitness are directly associated with increased mortality from CVD," write Hanna D. Margeirsdottir, MD, from the University of Oslo in Norway, and colleagues from the Norwegian Study Group for Childhood Diabetes. "One of the most common leisure time sedentary behaviors, television viewing, has been studied extensively in nondiabetic subjects.... To our knowledge, no studies have reported the influence of television watching on blood glucose control or CVD risk factors in children and adolescents with type 1 diabetes."

At 9 hospitals in the eastern part of Norway, 70% of eligible subjects participated in this study for a total of 538 children and adolescents. Time spent watching television and time spent using a computer were determined separately by interview, and other clinical data were also collected.

Mean age was 13.1 ± 3.7 years, mean diabetes duration was 5.4 ± 3.4 years, and mean HbA1C level was 8.6% ± 1.3% (reference range, 4.1% - 6.4%).

Sixty-two (11%) subjects had daily television viewing of less than 1 hour (mean HbA1C level, 8.2% ± 0.9%); 189 (35%) subjects, 1 to 2 hours (mean HbA1C level, 8.4% ± 1.2%); 166 subjects (31%), 2 to 3 hours (mean HbA1C level, 8.7% ± 1.4%); 75 subjects (14%), 3 to 4 hours (mean HbA1C level, 8.8% ± 1.2%); and 46 (9%) subjects, 4 or more hours (mean HbA1C level, 9.5% ± 1.6%; P < .001 for trend).

Even after adjustment for age, body mass index, and insulin dose, the association between television viewing and HbA1C level remained significant. There was no apparent correlation between HbA1C level and personal computer use.

"Extensive television watching is associated with poor blood glucose control in children and adolescents with type 1 diabetes," the authors write.

Study limitations include lack of data concerning physical activity, eating habits, other leisure activities apart from television viewing, or socioeconomic or psychological status.

"A potential implication of this study is to ask about the time spent watching television and other leisure activities, especially if the metabolic control of the children is poor," the authors conclude. "Improvement in long-term blood glucose control is important because it is a strong predictor of early coronary atherosclerosis and CVD events. Our findings lend support to the American Academy of Pediatrics' recommendation and suggest that encouraging children with type 1 diabetes to watch less television may be important for improved blood glucose control and better health outcomes."

The costs of publication of this article were defrayed in part by the payment of page charges, mandating that the article was therefore marked "advertisement" solely to indicate this fact.

Diabetes Care. 2007;30:1567-1570.

2007-06-11T07:30:00.000-07:00

Insulin Resistance, the Metabolic Syndrome, and Risk of Incident Cardiovascular Disease

Jørgen Jeppesen,MD, DMSc; Tine W. Hansen,MD, PhD; Susanne Rasmussen,MD, PhD; Hans Ibsen,MD, DMSc; Christian Torp-Pedersen,MD, DMSc; Sten Madsbad,MD, DMSc
J Am Coll Cardiol. 2007;49(21):2112-2119.
Posted 05/29/2007

Abstract and Introduction
Abstract
Objectives: The goal was to clarify if insulin resistance (IR) would predict cardiovascular disease (CVD) independent of the metabolic syndrome (MetSyn).
Background: Although the cause of MetSyn is not well defined, IR has been proposed to be an important cause. Only a small number of population-based studies have sought to clarify if IR predicts CVD independent of MetSyn.
Methods: This was a prospective Danish population-based study of 2,493 men and women, age 41 to 72 years, without major CVD at baseline. We defined MetSyn according to both the International Diabetes Foundation (IDF) and the National Cholesterol Education Program (NCEP) criteria, and we quantified IR by the homeostasis model assessment (HOMA-IR). Prevalence of MetSyn was 21% according to IDF criteria and 16% according to NCEP criteria. Accordingly, we defined IDF-HOMA-IR as belonging to the highest 21% of the HOMA-IR distribution, and NCEP-HOMA-IR as belonging to the highest 16% of the HOMA-IR distribution.
Results: Over a median follow-up of 9.4 years, the incidence of CV end points (CV death, nonfatal ischemic heart disease, and nonfatal stroke) amounted to 233 cases. In proportional hazard models, adjusting for age, gender, smoking, and low-density lipoprotein cholesterol, and with IDF-HOMA-IR and IDF-MetSyn included in the same model, the relative risk of an end point was 1.67 (95% confidence interval [CI] 1.22 to 2.29) for IDF-HOMA-IR and 1.16 (95% CI 0.84 to 1.60) for IDF-MetSyn. The corresponding figures for NCEP-HOMA-IR and NCEP-MetSyn included in the same model were 1.49 (95% CI 1.07 to 2.07) and 1.56 (95% CI 1.12 to 2.17).
Conclusions: In this Danish study, both HOMA-IR and NCEP-MetSyn were independent predictors of incident CVD.

Introduction
Although others had proposed similar concepts before 1988,[1,2] the Reaven[3] Banting lecture from that year, introducing the concept of syndrome X as a fundamental factor in the pathogenesis and clinical course of what are often referred to as the diseases of Western civilization–type 2 diabetes, hypertension, and atherosclerotic cardiovascular disease (CVD)–received much attention. Reaven's syndrome X originally consisted of resistance to insulin-stimulated glucose uptake, hyperinsulinemia, hyperglycemia, an increased concentration of very-low-density lipoprotein triglyceride, a decreased concentration of high-density lipoprotein cholesterol (HDL-C), and high blood pressure. Reaven[3] proposed that insulin resistance (IR) with compensatory hyperinsulinemia was the culprit in syndrome X.

Reaven's work inspired much research interest in the area.[1,2,4] Reaven[3] did not offer specific criteria for having syndrome X, and he did not include obesity or visceral obesity as a criterion. Later, others, including leading organizations and associations working in primary and secondary prevention of CVD, added measures of visceral obesity and offered specific criteria to define the metabolic syndrome (MetSyn).[1,4,5] Recently, however, the importance of the MetSyn as a risk factor of CVD and the role of IR as a cause of the MetSyn has become an issue for discussion.[1]

The purpose of the present study was to present an analysis of data from a large Danish population-based study dealing with some of the latest issues regarding the MetSyn and risk of CVD. We were particularly interested in clarifying if IR would predict incident CVD independent of the MetSyn, and how 2 different definitions of the MetSyn would affect the risk of CVD associated with the MetSyn and IR. We used the homeostasis model assessment (HOMA) to assess IR,[6,7] and we defined the MetSyn according to both the International Diabetes Foundation (IDF) criteria[5] and the National Cholesterol Education Program (NCEP) criteria.[4]

Methods
Study Population
In 1982 to 1984, a random sample of 4,581 men and women from the southwestern part of Copenhagen County were invited to participate in the Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA-1) health survey.[8] According to the MONICA protocol, participants were selected to represent an equal number of men and women age 30, 40, 50, and 60 years. Eventually, 3,785 (83.0%) participated. In 1993 to 1994, the MONICA participants were asked if they would be willing to participate in a new study. Since the first examination, 428 subjects had died and 23 had moved or could not be reached. Of the remaining 3,785 subjects, 2,656 (70.2%) were willing to participate in a new study protocol. The study was performed in the Research Center for Prevention and Health in Glostrup. All subjects completed a questionnaire about current and prior diseases, use of medication, and presence and absence of CVD risk factors. For the present study, 163 subjects with a previous diagnosis of myocardial infarction or stroke or taking digoxin or nitrates were excluded, leaving 2,493 men and women to be studied. The study was conducted in accordance with the Second Helsinki Declaration and approved by the Ethics Committee for Copenhagen Country. Written informed consent was obtained from all of the subjects.

Classification of Metabolic Status
For this study, we defined the MetSyn according to both the IDF[4,5] and the NCEP[4] criteria. Regarding the NCEP criteria, we used the latest version.[4] According to the IDF criteria with specific reference to a European population,[4,5] the MetSyn was based on the existence of a waist circumference ≥80 cm in women and ≥94 cm in men and 2 or more of the following components: 1) a fasting triglyceride concentration ≥1.7 mmol/l; 2) an HDL-C concentration <1.29 mmol/l in women and <1.03 mmol/l in men; 3) a blood pressure ≥130 mm Hg (systolic) or ≥85 mm Hg (diastolic) or use of antihypertensive drugs; and 4) a fasting plasma glucose ≥5.6 mmol/l or use of antidiabetic drugs. Based on the IDF criteria, 514 subjects (20.6%) had the MetSyn. According to the NCEP criteria, the MetSyn was based on the existence of 3 or more of the following components: 1) a waist circumference ≥88 cm in women and ≥102 cm in men; 2) a fasting triglyceride concentration ≥1.7 mmol/l; 3) an HDL-C concentration <1.30 mmol/l in women and <1.03 mmol/l in men; 4) a blood pressure ≥130 mm Hg (systolic) or ≥85 mm Hg (diastolic) or use of antihypertensive drugs; and 5) a fasting plasma glucose ≥5.6 mmol/l or use of antidiabetic drugs. Based on the NCEP criteria, 409 subjects (16.4%) had the MetSyn.

Regarding IR, we used HOMA to quantify IR (fasting glucose × fasting insulin/22.5).[6,7] The HOMA-IR values have been shown to correlate well with values obtained using the "gold standard" clamp technique.[7] We entered HOMA-IR both as a categoric variable and as a continuous variable in our analyses. Because the prevalence of the MetSyn was 20.6% according to IDF criteria and 16.4% according to NCEP criteria, we defined IDF-HOMA-IR as belonging (as closely as possible) to the highest 20.6% of the HOMA-IR distribution, and NCEP-HOMA-IR as belonging (as closely as possible) to the highest 16.4% of the HOMA-IR distribution. The reason we did this and did not use the usual definition of IR (highest 25%)[1,4] was that we did not want a priori to start our analyses knowing that around 4% or 9% of the defined insulin-resistant subjects would not be classified as having the MetSyn, depending on which definition of the MetSyn was used. We preferred to study and compare equal proportions in our categoric analyses to provide results that were easy to understand and interpret.

Measurements
Fasting concentrations of lipids, insulin, and glucose were analyzed by standard methods.[9,10] Blood pressure was measured in the sitting position after 5 min of rest using a random zero mercury sphygmomanometer. Determinations of body mass index (BMI), waist, hip, waist-to-hip ratio, heart rate, and alcohol intake, as well as subdivisions of the population according to smoking status and low or high level of physical activity, were done as described in detail elsewhere.[11]

End Points
Complete follow-up regarding death was obtained through information from the Civil Registration System. Information on cardiovascular mortality was obtained from blinded classification of death certificates, and information on hospitalizations was recorded from the Danish National Health Register, which is known to have high sensitivity and predictive value.[12] The prespecified end point was the combination of cardiovascular mortality, ischemic heart disease (ICD-8 codes 410 to 414 or ICD-10 codes I20 to I25), and stroke (ICD-8 codes 431, 433, and 434 or ICD-10 codes I61 and I63).

Statistical Analysis
All analyses were performed with the Statistical Analysis System, version 9.1 (SAS Institute, Cary, North Carolina). Baseline characteristics, presented as median and 5% to 95% percentiles or as percent, were compared with nonparametric rank sum tests for continuous variables and chi-squared tests for categoric variables. Spearman correlation coefficients analysis was used to assess the relation between IR and the continuously distributed individual components of the MetSyn. Survival was analyzed with Cox proportional hazard models. In the outcome analysis, for participants who experienced multiple events we only considered the first. The assumption of linearity was assessed by demonstrating that inclusion of variables representing quintiles did not improve the model. Interaction was tested with a likelihood ratio test and the proportional hazard assumption was tested by demonstrating no importance of variables multiplied by time as time-dependent variables.[13] Population-attributable risk estimates were calculated as described in detail elsewhere.[14] All statistical tests were 2-sided and the significance level was chosen as p < 0.05.

Results
Baseline characteristics of the participating women and men are summarized in Table 1 . In total, 2.6% had fasting glucose levels ≥7.0 mmol/l, and 1.0% had fasting glucose levels ≥10.5 mmol/l. The median (range) of HOMA-IR was 6.2 (0.8 to 201.1) U. Based on both IDF and NCEP criteria, the male participants had a higher prevalence of the MetSyn, and they also had higher HOMA-IR values and higher levels of fasting insulin.

Table 2 describes the baseline characteristics of the participants according to definition of the MetSyn and definition of IR. It is seen in Table 2 that the frequency of concordance among those individuals with the MetSyn and IR only amounted to 52.6% and 56.5%, depending on which definition of the MetSyn was used.

Table 3 shows the correlation coefficients between HOMA-IR and the continuously distributed individual components of the MetSyn, including fasting insulin.

The median study duration, from baseline evaluation until follow-up on October 1, 2003, was 9.4 years (5th to 95th percentile interval 4.0 to 10.1 years). In the follow-up period, 233 end points were recorded: 56 cardiovascular deaths, 140 coronary events (including 66 acute myocardial infarctions), and 37 strokes. The incidence of a cardiovascular end point was 14.6% in participants with the MetSyn based on IDF criteria and 16.6% in participants with the MetSyn based on NCEP criteria. Because we found no gender-based difference (p = 0.46) in the relationships between MetSyn and IR and risk of CVD, we pooled all of the data together in our outcome analysis to increase power.

Table 4 shows the relationship between the MetSyn based on IDF criteria, IDF-HOMA-IR, HOMA-IR as a continuous variable, and risk of CVD, adjusted for age, gender, smoking, and low-density lipoprotein cholesterol (LDL-C). It is seen that, when entered individually in the models, both the MetSyn and IDF-HOMA-IR were significant predictors of a cardiovascular end point. However, when entered with IDF-HOMA-IR in the same model, the MetSyn based on IDF criteria was no longer a significant predictor of CVD. It is also seen in Table 4 that the results were the same when HOMA-IR was entered as a continuous variable.

Table 5 shows the relationship between the MetSyn based on NCEP criteria, NCEP-HOMA-IR, HOMA-IR as a continuous variable, and risk of CVD, adjusted for age, gender, smoking, and LDL-C. When entered individually in the models, both the MetSyn and NCEP-HOMA-IR were significant predictors of risk of a cardiovascular end point. When entered with NCEP-HOMA-IR in the same model, both the MetSyn based on NCEP criteria and NCEP-HOMA-IR were significant predictors of CVD. It is also seen in Table 5 that the results were the same when HOMA-IR was entered as a continuous variable.

Table 6 shows the hazard ratios (HRs) of CVD of the various components in the MetSyn compared with their respective counterparts in multivariate models adjusted for age, gender, smoking, and LDL-C.

Additional Analyses
Repeating the analyses excluding subjects with diabetes, based on either history, use of antidiabetic drugs, or fasting glucose ≥7.00 mmol/l (n = 73; 2.9%) did not change the results much. When the MetSyn based on IDF criteria and IDF-HOMA-IR were included in the same model and adjusted for age, gender, smoking, and LDL-C, the HRs were 1.16 (95% confidence interval [CI] 0.83 to 1.63; p = 0.39) and 1.56 (95% CI 1.12 to 2.18; p = 0.009), respectively. When the MetSyn based on NCEP criteria and NCEP-HOMA-IR were included in the same model and adjusted for age, gender, smoking, and LDL-C, the HRs were 1.48 (95% CI 1.05 to 2.12; p = 0.027) and 1.39 (95% CI 0.98 to 1.99; p = 0.066), respectively. Finally, when HOMA-IR was entered as a continuous variable with the MetSyn based on either IDF or NCEP criteria in the model described above, HOMA-IR was significantly related to risk of CVD with HRs of 1.025 (95% CI 1.010 to 1.040; p = 0.0013) and 1.020 (95% CI 1.005 to 1.036; p = 0.011), respectively, per unit increase.

We also examined the relationship between IR and the MetSyn and risk of CVD with adjustment for the Framingham risk score.[15] The median Framingham risk score value with 5% to 95% percentiles was 7 points (-1 to 12). As seen in Table 7 and Table 8 , IDF-HOMA-IR, the NCEP definition of the MetSyn, NCEP-HOMA-IR, and HOMA-IR entered as a continuous variable were all significant predictors of incident CVD after adjustment for the Framingham risk score.

We also calculated population-attributable risk estimates.[14] Based on a model including age, gender, smoking, and LDL-C and entering the various definitions of the MetSyn and IR individually, the population-attributable risk estimate was 8.7% for the IDF definition of the MetSyn, 13.9% for IDF-HOMA-IR, 12.4% for the NCEP definition of the MetSyn, and 11.8% for NCEP-HOMA-IR. In comparison, age (>60 years), male gender, and smoking accounted for more than 60% of all CVD events in the present study population.

Finally, we found no interactions regarding the MetSyn, gender, age, or its individual components.

Discussion
The present study provided interesting results: 1) IR predicted incident CVD independent of the MetSyn based on either IDF or NCEP criteria; 2) adjusted for IR, the MetSyn based on NCEP criteria was a significant predictor of CVD, whereas the MetSyn based on IDF criteria was not; 3) the MetSyn and IR were significant risk factors of CVD in the nondiabetic population; 4) IR, defined as belonging to the highest 20.6% of the HOMA-IR distribution, predicted incident CVD independent of the Framingham risk score with an approximate 1.5-fold increased risk; and 5) the rate of concordance among those individuals with the MetSyn and IR amounted to around 50%.

Recently, the importance of the MetSyn as a risk factor of CVD and the role of IR as a cause of the MetSyn has become an issue for discussion.[1] Although several large population-based studies found that subjects with the MetSyn had an increased risk of CVD independent of traditional risk factors,[16-22] the value of the MetSyn as a risk factor of CVD has been questioned,[1] because it was shown in several population-based studies that risk score programs such as the Framingham risk score provided more information of global risk of CVD than the MetSyn.[23-26] However, that analysis could be misleading. Risk score programs include predictors of CVD that are independent of the MetSyn, such as age, gender, and smoking, the leading causes of CVD in the community.[25,27] Also, in the present study, old age (>60 years), male gender, and smoking accounted for more than 60% of all CVD events. In comparison, the MetSyn based on IDF criteria accounted for 8.7% of all CVD events and the MetSyn based on NCEP criteria accounted for 12.4% of all CVD events. In our study, the MetSyn based on NCEP criteria and both IDF-HOMA-IR and NCEP-HOMA-IR predicted incident CVD independent of the Framingham risk score, but the increased risk associated with the NCEP definition, IDF-HOMA-IR, and NCEP-HOMA-IR only corresponded to an increase in Framingham risk score of approximate 2 points, so it is obvious that also in our study population a risk score program, such as the Framingham risk score, provided more information of global risk of CVD than the MetSyn and IR.

Although IR has been proposed as an important cause of the MetSyn, the present results showed that other causes must be present. Accordingly, the rate of concordance among those individuals with the MetSyn and IR only amounted to around 50%, and the correlation coefficients between HOMA-IR and the continuously distributed components of the MetSyn were not that high either, as seen in Table 3 . However, based on the medical literature,[2-4] it is reasonable to believe that IR is a major cause of the MetSyn, although the exact percentage of MetSyn cases caused by IR remains to be defined.

Another issue regarding the value of the MetSyn as a risk factor of CVD involves the many different definitions of the syndrome.[1,4,5] In the present study, we examined how 2 different definitions of the MetSyn influenced the risk of CVD associated with the MetSyn and IR. We found that the MetSyn based on IDF criteria was no longer a significant predictor of CVD after adjustment for IDF-HOMA-IR or HOMA-IR, whereas both the MetSyn based on NCEP criteria and NCEP-HOMA-IR or HOMA-IR were all significantly related to CVD risk when entered in the same model. Owing to the overlap of subjects between the various groups defined to have the MetSyn and/or IR, it was difficult to formally compare differences between the groups statistically, so the only reasonable conclusion to draw was that IR predicted CVD events independent of the MetSyn.

So far, several studies have been published focusing on IR and risk of incident CVD.[26,28-33] It is a major limitation of the present study that we used a surrogate measure of IR and not a "gold standard" technique to quantify IR. However, there exists only 1 large population-based prospective study that has used "gold standard" techniques to study the relation between IR and risk of incident CVD: the Uppsala Longitudinal Study of Adult Men (USLAM).[33,34] In a cohort of 815 men, age 70 years at baseline, with a follow-up of up to 10 years, IR as determined by the euglycemic clamp technique predicted incident coronary heart disease with adjustment for serum cholesterol, fasting plasma glucose, BMI, and smoking.[33] However, in the USLAM cohort, no data were presented regarding the relationship between IR and CVD after adjustment for the components of the MetSyn or the MetSyn itself.[33,34] In a small study of healthy subjects, IR as determined by the insulin suppression test ("gold standard" technique) was a strong predictor of CVD independent of all other major risk factors of CVD.[32] In the other population-based prospective studies,[26,28-31] the method used to quantify IR was the HOMA model.[6,7] The results in those studies were mixed, showing significant independent relationships between HOMA-IR and incident CVD in some[28,29] but not all[26,30,31] of the studies after adjustment for traditional risk factors, including the components of the MetSyn or the MetSyn itself.

In conclusion, what is the situation with the MetSyn and IR after the present findings? Regarding the MetSyn as a risk factor of CVD, it is obvious that risk score programs such as the Framingham risk score provides more information about global risk of CVD compared with the MetSyn. However, because the MetSyn based on NCEP criteria in the present study was associated with an around 50% increased risk of CVD adjusted for the Framingham risk score, our results support the view of the NCEP panel[4] that the MetSyn will help with the evaluation of individuals at low or moderate risk by the Framingham risk score who warrant intervention based on the presence of MetSyn. Regarding IR as the cause of the MetSyn and the associated adverse cardiovascular consequences, the present results indicate that IR may by the cause of around 50% of the MetSyn cases, but the fact that IR was identified as an independent risk factor of CVD adjusted for the MetSyn or the Framingham risk score indicates the IR may indeed be a factor in the pathogenesis of CVD. However, because HOMA-IR values have not yet been standardized for routine use, the clinician will probably continue to use the MetSyn and not consider measures of IR, because the MetSyn is much easier and more practical to apply in the typical clinical setting. Nevertheless, we think that IR is an important concept, because IR, similar to a high LDL-C level, seems to represent a basic pathophysiologic pathway leading to potentially preventable CVD in the community.[4] However, we have to acknowledge at this stage that because no large randomized clinical trial has demonstrated that reducing the level of IR improves CVD outcome, the best thing to do to help persons with IR would be to focus on proven interventions, such as lowering LDL-C, blood glucose, and blood pressure, to reduce the risk of CVD in this high-risk population.[4]

2007-06-10T09:17:00.000-07:00

Complications of Diabetes Insipidus: The Significance of Headache

Mary Jane Hudson, MSN, RN
Pediatr Nurs. 2007;33(1):58-59.
Posted 05/14/2007

Introduction and Medical History

Introduction
Travis was a 10-year-old with panhypopituitarism and recent resection of a craniopharyngioma. One week after discharge, his parents telephoned to report that Travis was complaining of neck and back pain. They were instructed to bring Travis to the hospital immediately. Upon arrival in the Pediatric Clinic, blood was drawn for laboratory tests and intravenous access was obtained. When sodium levels were reported as 181, Travis was admitted to the Pediatric Intensive Care Unit (PICU).

Medical History
Travis was a healthy young boy until recently when he started complaining of headaches. He was diagnosed with panhypopituitarism and craniopharyngioma. Subsequently, Travis underwent surgical resection of the tumor. Fluctuating sodium levels complicated his immediate postoperative hospital course. Travis had developed diabetes insipidus following the removal of his craniopharyngioma, resulting in extremely high and fluctuating postoperative sodium levels. During his initial postoperative hospital stay, Travis' sodium levels gradually were controlled with intravenous fluids and desmopressin. After his sodium levels were stabilized within normal limits, Travis was discharged on oral desmopressin. Once home, Travis was relatively immobile, gained weight, and spent most of his time in bed and only occasionally left his room or his house.

Assessment Findings
Travis arrived in the PICU complaining of neck and back pain. The following initial assessment findings were noted:
Vital Signs: Temp – 39.5oC, HR – 212, RR – 72, BP – 119/65 (89), O2 sat – 96% on room air, Weight – 27.6 kg.
Neurological: Lethargic, oriented, PERRL.
Pain: Acute, constant, aching pain in neck, back and extremities; pain rating of 10/10 on numeric scale.
Respiratory: Tachypneic, symmetrical, clear, irregular, labored, grunting, 1-liter oxygen via nasal cannula.
Cardiovascular: Sinus tachycardia, pulses present, generalized edema, capillary refill sluggish.
Musculoskeletal: Spontaneous but limited movement of all extremities due to pain.
Gastrointestinal: Abdomen soft & distended; active bowel sounds, adipsia, no hunger.
Genitourinary: Clear, pale yellow, polyuria, and specific gravity 1.005.
Integumentary: Warm, pale.

Management Plan
A peripheral intravenous line was initiated and intravenous normal saline was started in the Pediatric Clinic. Pain medication was administered and Travis was placed on 1 liter of oxygen via nasal cannula before transfer to the PICU. Upon arrival in the PICU, his initial chemistry laboratory values were reported as follows: glucose 175, sodium 181, potassium 4.7, chloride 145, carbon dioxide 18, blood urea nitrogen 30, creatinine 1, calcium 9.8, albumin 5.3, Alk 137, Alt 134. The initial complete blood count (CBC) results were: WBC 9.3, RBC 3.09, Hgb 7.5, Hct 25.3 and Plt 315.

A second peripheral intravenous line of D51/2 NS was initiated. Initiation of an arterial line was attempted without success. Blood cultures were drawn and cerebrospinal fluid analysis from lumbar puncture (LP) was performed. Travis was sent for a computed tomography (CT) scan and magnetic resonance imaging (MRI). What do you think is causing Travis to decompensate and have neck and back pain?

Continuing Medical Management
The blood cultures and LP were negative but the MRI showed a sagittal sinus thrombosis. A heparin drip was initiated after a bolus was administered and Travis remained on a heparin drip with several rate adjustments. Several hours after admission to the PICU, the laboratory reported a serum osmolality of 392. At that time, a diagnosis of recurrent or worsened central diabetes insipidus was made. The therapeutic plan was to slowly lower his sodium level while maintaining an appropriate fluid balance. Repeated sodium levels fluctuated between 159 and 178, but by the following day with continuous isotonic intravenous therapy, gradually decreased to the 140 range.

Over the next several days, Travis became less lethargic and vocalized hunger. His back and neck pain were greatly decreased and he reported pain scores of 0 to 3/10. Travis' heart rate and respiratory rate also began to slowly decrease. He was eventually transferred to an acute care unit and discharged to home after 2 weeks of close monitoring and treatment.

Pathophysiology
Sodium is the main extracellular ion that regulates the osmotic pressure in the cells and body fluids. Water and sodium interact to control intravascular volume. Water balance usually determines the concentration of sodium and sodium acts as a buffer to prevent an excessive loss of water from the tissues. Hypernatremia is defined as an elevation in the concentration of serum sodium above 145 mEq/L and is always indicative of dehydration. Signs and symptoms of hypernatremia include irritability, restlessness, weakness, lethargy, fever, hyperglycemia, headache, and seizures. Hypernatremia has also been associated with adipsia in 50% of patients with hypothalamic tumors. Thirst, however, usually prevents severe hypernatremia unless water intake is restricted or water resorption is reduced (Behrman, Kleigman, & Jenson, 2004; Workeneh, Balakumaran, Bichet & Mitch, 2004).

Hypernatremic dehydration can develop in patients with central diabetes insipidus when the patient does not drink adequately. An elevated osmolality (> 295) normally causes the secretion of antidiuretic hormone (ADH). Diabetes insipidus (DI) is an ADH deficiency disorder of the hypothalamus. The hypothalamus, which is responsible for regulating water balance, secretes ADH that is subsequently released from the pituitary gland into the bloodstream. ADH tells the body to conserve the right amount of water to prevent dehydration.

Causes of deficient amounts of ADH secretion include: (a) a malfunctioning hypothalamus or pituitary gland, (b) damage to the hypothalamus or pituitary gland during surgery, (c) endocrine and metabolic disorders, (d) brain injury, (e) tumor, (f) tuberculosis, and (g) meningitis. Disturbances and disorders of the hypothalamus result in insufficient secretion of ADH. If too little ADH is secreted, fluid and electrolyte imbalance occurs, resulting in water not being reabsorbed, and in excessive, dilute urine production, sodium retention and dehydration (Makaryus & McFarlane, 2006; Robertson, 2003; The Diabetes Insipidus Foundation, 2003).
Dehydration is a decrease in the extracellular fluid volume that results in electrolyte imbalance.

Signs of dehydration include increased temperature, tachycardia, tachypnea and lethargy. The type of dehydration is determined by the serum sodium concentration. Hypernatremic dehydration is the most devastating type of dehydration because it can result in severe neurological damage from hemorrhage. Normally, an increased osmolality results in water conservation. This does not occur in central DI due to a malfunctioning hypothalamus. In hypernatremic dehydration, extracellular osmolality increases and water moves out of the brain cells. This movement of water causes brain cells to shrink and the blood vessels tear as the brain is pulled away from the skull and the meninges. The tearing of blood vessels results in hemorrhaging and potential for thrombus formation (Behrman et al., 2004).

The torn blood vessels are repaired as the platelets migrate and stick to the injured cells to form a thrombin plug. The thrombin plug is converted to a fibrinous deposit on the cell to stop the hemorrhaging. Thrombus formation is greatly affected by the stasis or turbulence of blood flow. With sluggish blood flow, more platelets stick and additional fibrin is deposited to create congestion and edema in the obstructed vessel. The obstructed, fibrin-filled blood vessels constrict blood flow and subsequently cause pain at the site and distal to the site of the thrombus (Kumar, Abbas, & Fausto, 2005).

The combination of surgical manipulation of the hypothalamus, physical inactivity, and hypernatremic dehydration with central diabetes insipidus are major factors in thrombus formation. After the hypothalmus is surgically manipulated, management includes closely monitoring body water and electrolyte balance as well as a medication regimen. In diabetes insipidus, hypernatremic dehydration can develop as the result of an inadequately monitored therapeutic regimen. In Travis' case, his postoperative diabetes insipdius was inadequately monitored and his physical inactivity together with restricted fluid intake resulted in inadequate resorption of water, impaired blood circulation and sagittal sinus thrombus formation as a complication of his hypernatremic dehydration.

Family Matters
Travis was the product of a term delivery without prenatal complications. Travis lived with his mother, father, older brother and younger sister. His parents were very involved in his care and have been physically and emotionally drained since Travis was diagnosed with craniopharyngioma. Travis was a child who required constant emotional support and relied heavily on his mother to provide reassurance and tend to all of his needs. He was a very emotionally fragile child who communicated his needs by mumbling through tears.

The Rest of the Story
During this PICU admission, Travis' hypernatremia was resolved with intravenous hydration and desmopressin. Travis was discharged on enoxaparin (Lovanox) via insuflon catheter. His parents were instructed on the use and care of the insuflon catheter. Other discharge instructions included weekly checks of his enoxaparin and sodium levels as well as drinking at least four 12-ounce glasses of fluid per day.

Home nursing visits were ordered to assess Travis' progress and evaluate his home regimen. Goals of the home nursing care included: 1) changing insuflon catheter once a week, 2) instructing Travis and his family about his medications, diet and fluid intake, and safety factors related to diabetes insipidus and the potential complications of dehydration, and 3) assessing vital signs and evaluating management of Travis' disease process. Since Travis had been immobile since his surgery, physical therapy was ordered to facilitate ambulation and improve his joint and muscle strength. Over the past several months, Travis has been stable. He has been constantly and closely monitored by endocrinology and has maintained his sodium level within normal range.

The Lesson Learned
Manipulation of the hypothalamus for removal of a tumor results in 90% neuron death that eventually leads to permanent central diabetes insipidus in 70% to 90% of patients during the postoperative period (Behrman et al., 2004;Ghirardello, Hopper, Albanese, & Maghnie, 2006). Early recognition and management of the child with diabetes insipidus demands extremely close monitoring of fluid and electrolyte balance to prevent the complications associated with hypernatremia and dehydration. Nurses need to be attuned to the subtle changes in electrolytes and water balance in patients diagnosed with hypothalamic disorders. An inadequately monitored therapeutic regimen of patients with diabetes insipidus can quickly lead to complications of hypernatremic dehydration and thrombus formation.

References
Behrman, R., Kliegman, R., & Jenson, H. (2004). Nelson textbook of pediatrics (17th edition) (pp. 193 – 199, 245 – 249, 1650, 1656, 1853 – 1855, 2036 – 2037). Philadelphia: Saunders, An Imprint of Elsevier.
Ghirardello, S., Hopper, N., Albanese, A., & Maghnie, M. (2006). Diabetes insipidus in craniopharyngioma: Postoperative management of water and electrolyte disorders. Journal of Pediatric Endocrinology, 19(Suppl. 1), 413 – 421.
Kumar, V., Abbas, A., Fausto, N. (2005). Robbins and Cotran: Pathologic basis of disease (7th edition) (pp. 124-125). Philadelphia: Saunders, An Imprint of Elsevier.
Makaryus, A., & McFarlane, S. (2006). Diabetes insipidus: Diagnosis and treatment of a complex disease. Cleveland Clinic Journal of Medicine, 73 (1), 65 – 71.
Robertson, G. (2003). What is diabetes insipidus? Retrieved on July 5, 2006 from http://www.diabetesinsipidus.org/whatisdi.htm.
The Diabetes Insipidus Foundation, Inc. (2003). Polyuria and polydipsia: Think of diabetes insipidus (DI) - not just diabetes mellitus. Retrieved on June 30, 2006 from http://www.diabetesinsipidus.org/polydipsia_polyuria.htm.
Workeneh, B., Balakumaran, A., Bichet, D., & Mitch, W. (2004). The dilemma of diagnosing the cause of hypernatraemia: Drinking habits vs diabetes insipidus. Nephrology Dialysis Transplantation, 19 (12), 3165 – 3167.
Mary Jane Hudson, MSN, RN, Clinician IV University of Virginia Health Science Center Charlottesville, VA

2007-06-10T09:14:00.000-07:00

The Participation of Children in Nontherapeutic Diabetes Research in the US

[Viewpoint]
Lainie Friedman Ross

Nat Clin Pract Endocrinol Metab. 2007;3(5):378-379.
Posted 05/16/2007

Introduction

The spectrum of diabetes in children has expanded from type 1 diabetes mellitus to include permanent and transient forms of neonatal diabetes, maturity-onset diabetes of youth, and obesity-associated type 2 diabetes mellitus in late childhood.[1] Research must be performed in these populations to improve the care of children with diabetes; however, studies that enroll children raise many ethical and regulatory questions, as children are vulnerable and cannot provide informed consent for themselves. These questions are further complicated when the study does not offer the prospect of direct benefit to the participant (i.e. nontherapeutic research). In this Viewpoint, I will explore the ethical issue of enrolling children in nontherapeutic diabetes research.

All federally funded clinical research in the US that involves human participants must conform to the Code of Federal Regulations (CFR) Common Rule, 45 CFR Part 46, Subpart A,[2] and most non-federally funded research voluntarily complies with these regulations. When the research involves children, however, additional protections apply (45 CFR Part 46, Subpart D).[3] Research that falls within Subpart D is distinguished by the level of risk and whether the study presents the prospect of direct benefit to participants. This categorization affects whose consent is necessary, whether the child's dissent is binding, and whether national review is necessary.[3]

The first category—research that does not involve greater than minimal risk (CFR §46.404)—requires only one parent's permission and the assent of the child. CFR §46.405 involves research with greater than minimal risk, but with the prospect of direct benefit to individual participants. This category also only requires one parent's permission and the child's assent, although the child's dissent can be overridden. CFR §46.406 addresses research that involves greater than minimal risk and no prospect of direct benefit to individual participants who have the disorder or condition that is being studied, but about which generalizable knowledge might be gained; permission from both parents and the child's assent are required for this category of research. Research that involves healthy children, entails more than minimal risk, and does not offer the prospect of direct benefit cannot be approved by a local institutional review board (IRB). Instead, such research can only be approved by a panel of experts convened by the Secretary of the Department of Health and Human Services under CFR §46.407.[3] These panels are known as '407 panels'; they act as a national review board.

The inclusion of control participants is desirable for many research studies. Nevertheless, the regulations are clear: if the research involves more than minimal risk and offers no prospect of direct benefit, then the local IRB can approve the research only if it entails at most a minor increase over minimal risk; the children have a disorder or condition; and the research will yield generalizable information about this disorder or condition. In practical terms, therefore, the regulations provide greater protection to healthy children (for whom a local IRB can only approve research that entails at most minimal risk) than to children with a disorder or condition.

This distinction might be justified by the argument that children with a disorder or condition have benefited from the previous research participation of other children with this same disorder or condition, and so they have an obligation to participate in studies that will benefit future children. The problem with this argument is that if there is a moral duty to help future generations, it is at best imperfect, and no particular child has a strict obligation to participate in research.[4] Indeed, a strong argument can be made that children with a disorder or condition are more vulnerable than healthy children and deserve special protection. Consequently, the regulations should provide affected children with greater protection (or at least equal protection) than that afforded to their healthy counterparts.[5] This position was expressed by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research during the initial debates around Subpart D. Commissioner Robert H Tuttle argued that children with a disorder cannot be deemed a morally relevant separate class for the purposes of relaxing protective measures.[6] Instead, the Commissioner emphasized that if sick children could be deemed a morally relevant separate class, surely they would deserve special protection given their vulnerable state.[6]

If healthy children and those with a disorder should be held to the same standard, the question remains what that standard should be. Under the current regulations, this standard would be no more than minimal risk for research that does not offer the prospect of direct benefit. The consequence would be that most diabetes research on children could not be approved locally, as any research that involves intravenous glucose tolerance tests or a drug not approved for use in healthy children would be excluded. All such research would have to undergo 407 review. One way to resolve the problem would be to revise what research constitutes a minimal risk for children. Minimal risk is currently only defined in Subpart A (the Common Rule) and not in Subpart D (additional protection for children). Robert Nelson and I have, therefore, suggested a definition of minimal risk for children that would include most research currently classified as minimal risk and a minor increase over minimal risk.[7]

What about the 'at-risk' child? If a black child is obese and has obese parents who have type 2 diabetes mellitus, the American Diabetes Association classifies this child as at increased risk of developing type 2 diabetes mellitus.[8] Researchers would want to carry out research to understand what factors protect such children or make them more vulnerable. Alternatively, a child with genetic susceptibilities could be at increased risk for type 1 diabetes mellitus.[9] Again, researchers would want to study why some children with these genetic susceptibilities go on to develop diabetes, whereas others do not. The current regulations do not address at-risk children, but only state that a child must have a disorder or condition, or the research can pose no more than minimal risk. This omission can be explained in part by the fact that genetic predispositions were not as clearly understood when the regulations were written as they are today. These examples show that health and illness can no longer be understood as polar extremes, but instead represent two points along a continuum. These examples also show why it is necessary to revise the regulations to allow such children to participate in research that entails a minor increase over minimal risk. One solution is the revision of the definition of minimal risk as proposed above.[7] An alternative solution is to revise the current interpretation of a 'disorder or condition' to include those children 'at risk for a disorder or condition'. Depending on how broadly 'at risk' is interpreted, these solutions could lead to the same result: a single standard of permissible risk for all children.

In conclusion, research that involves children is necessary for the advancement of pediatric medicine, and yet children are vulnerable individuals who must be protected. Current federal regulations clearly need to be revised in order to achieve the proper balance of access versus protection for all children.

References
Soltesz G (2003) Diabetes in the young: a paediatric and epidemiological perspective. Diabetologia 46: 447-454
United States Department of Health and Human Services 45 CFR Part 46, Subpart A [http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46. htm#subparta] (accessed 12 March 2007)
United States Department of Health and Human Services 45 CFR Part 46, Subpart D [http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46. htm#subpartd] (accessed 12 March 2007)
Kant I (1964) Groundwork of the Metaphysic of Morals, 30-33 [translator HJ Paton]. New York: Harper & Row
Ross LF (2003) Do healthy children deserve greater protection in medical research? J Pediatr 142: 108-112
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1977) Report and Recommendations: Research Involving Children, 146-153. Washington DC: US Printing Office, Department of Health, Education and Welfare Publication No. (OS) 77-0004
Nelson RM and Ross LF (2005) In defense of a single standard of research risk for all children. J Pediatr 147: 565-566
American Diabetes Association (2000) Type 2 diabetes in children and adolescents. Pediatrics 105: 671-680
Ronningen KS (1997) Genetics in the prediction of insulin-dependent diabetes mellitus: from theory to practice. Ann Med 29: 387-392

Disclaimer
The author declared she has no competing interests.

Reprint Address
Correspondence MacLean Center for Clinical Medical Ethics, University of Chicago, 5841 S Maryland Avenue, MC 6089, Chicago, IL 60637, USA. Email lross@uchicago.edu

Lainie Friedman Ross is the Carolyn and Matthew Bucksbaum Professor of Clinical Medical Ethics, the Associate Director of the MacLean Center for Clinical Medical Ethics, and the Chief of the Section of Community Health Sciences, Institute for Molecular Pediatric Sciences, University of Chicago, Chicago, IL, USA.

2007-06-10T09:08:00.000-07:00

The "Top 10" Drug Errors and How to Prevent Them

by Kathryn L. Hahn, PharmD
Selection from: Highlights of the American Pharmacists Association 2007 Annual Meeting

Introduction
More than 7000 pharmacists gathered in Atlanta, Georgia, for the American Pharmacists Association (APhA) 2007 Annual Meeting to explore new challenges and the latest advances in pharmacy. Among the more than 80 programs presented were several sessions that dealt with reducing medication errors and adverse events, a topic that has received widespread media attention.

In addition, the author of a critically acclaimed book on drug errors was on-site to discuss his book and to autograph copies for attendees. Michael R. Cohen, RPh, MS, ScD, DPS, is President of the Institute for Safe Medication Practices (ISMP) and author of Medication Errors, which was published by the APhA.

Conference participants learned about common medication errors, steps to avoid or eliminate them, strategies to communicate effectively with prescribers, and ways to recognize and reduce stressful situations in the pharmacy workplace that may contribute to medication errors.

"Top 10" Medications Involved in Adverse Events

The Institute of Medicine (IOM) published findings in 1999 on the quality of healthcare in America. That report, "To Err Is Human: Building a Safer Health System," concluded that as many as 7000 Americans die from medication errors each year.[1] In July 2006, the IOM released a new report, "Preventing Medication Errors," stating that the frequency of medication errors and related injuries was still a serious concern.[2]

A common question that arises is: "What drugs are most often involved in medication errors?" Matthew Grissinger, RPh, FASCP, is a medication safety analyst with ISMP, the nation's oldest voluntary drug error reporting program, located in Huntingdon, Pennsylvania. His session on "The Top 10 Adverse Drug Reactions and Medication Errors" drew an audience that filled the meeting hall.[3]

Grissinger first referred to a study that identified the 10 drugs most commonly implicated in adverse events requiring treatment in a hospital emergency department (ED).[4] The study also documented the frequency with which each of the 10 drugs was involved:

Insulin (8%);
Anticoagulants (6.2%);
Amoxicillin (s) (4.3%);
Aspirin (2.5%);
Trimethoprim-sulfamethoxazole (2.2%);
Hydrocodone/acetaminophen (2.2%);
Ibuprofen (2.1%);
Acetaminophen (1.8%);
Cephalexin (1.6%); and
Penicillin (1.3%).

Unintentional overdoses made up 40% of these ED visits, representing the most prevalent mechanism of injury by far. Other mechanisms included side effects and allergic reactions. Some of the drugs on this list are especially common (eg, hydrocodone and amoxicillin), so the sheer volume of prescriptions written is a major factor.

The elderly also play a key role in this issue, as they account for 34% of all written prescriptions. The average number of prescriptions for an elderly person in the United States in 2000 was 28.5 per year. That number is estimated to reach 38.5 by the year 2010. Almost a quarter million seniors are hospitalized every year due to reactions between prescription and over-the-counter (OTC) medications.

Common misuses that lead to adverse drug events are taking incorrect doses, taking doses at the wrong times, forgetting to take doses, or stopping the medication too soon (all nonadherence issues). An example of commonly misused medications can be seen with arthritis therapies.

Seventy million Americans suffer from arthritis and joint pain, which translates into 30 million people taking nonsteroidal anti-inflammatory drugs, either prescription or OTC. Misuse of these drugs leads to 103,000 hospitalizations and 16,000 deaths per year. Unnecessary use of nonsteroidal anti-inflammatory drugs also increases avoidable side effects, such as dyspepsia, peptic ulcer, and gastrointestinal bleeding.

Another high-volume prescription class is the antibiotics. This group represents significant inappropriate prescribing: Twenty-three million antibiotic prescriptions are written for colds, bronchitis, and upper respiratory infections each year, Grissinger said, despite the fact that antibiotics don't kill viruses.

Top 10 Medications Involved in Drug Errors

A somewhat different top 10 list identifies medications that are most commonly misused or mishandled in some way by healthcare professionals. This list is based on information from the United States Pharmacopoeia (USP), which maintains a database of medication errors that are reported anonymously. The figures represent drug errors associated with acute hospital care[5]:

Insulin (4% of all medication errors in 2005);
Morphine (2.3%);
Potassium chloride (2.2%);
Albuterol (1.8%);
Heparin (1.7%);
Vancomycin (1.6%);
Cefazolin (1.6%);
Acetaminophen (1.6%);
Warfarin (1.4%); and
Furosemide (1.4%).

Hospitals and healthcare systems use the USP database to track medication errors and identify trends. Drug errors are defined as unintentional acts committed by healthcare providers involving medications. Grissinger noted that comparable data are unavailable for outpatient care.

The number 1 error-prone medication is insulin. In fact, a 1998 ISMP study found that 11% of all serious medication errors involve insulin misadministration.[6] Errors include mixing up products with similar packaging (look-alike products); confusing generic listings on computer databases; similarity in names (eg, Humalog and Humulin); and most importantly, confusing the abbreviation "u" for units with the number 0. ISMP reports that these errors have been occurring for over 30 years.

The second drug on this list is morphine, which can be extrapolated to include all opioids, Grissinger said. Similar names for some of these drugs often cause confusion, such as:

Avinza and Evista;
Morphine and hydromorphone;
Oxycontin and MS Contin;
Hydrocodone and oxycodone; and
Oxycodone and codeine.

In the community pharmacy, these drugs often are stacked close together in a locked area, and many have similar packaging, making it easy to grab the wrong one when dispensing. Another common mistake is mixing up oxycodone with oxycodone ER (extended release), especially in handheld device order entry.

Morphine oral solutions cause many problems because of the multiple concentrations that are available, all stored close to each other. For example, it would be easy to confuse "mL" with "mg"; using 5 mL of morphine 20 mg/mL (100 mg) instead of the prescribed 5 mg (0.25 mL) would lead to overdosing the patient. Alternatively, an intended dose of 1 mL of morphine 20 mg/mL (20 mg) might be given as 1 mL of 10 mg/5 mL (2 mg), thus underdosing the patient. Grissinger also reported a case in which Avinza (morphine ER caps) 30 mg was misinterpreted and dispensed as "qid" (4 times daily) instead of "qd" (once daily), causing a near-fatal overdose.

Acetaminophen is another drug on the error list that causes many problems. It is available in many different strengths, and various measuring devices are available for dispensing it. In addition, it is found in many combination medications, both prescription and OTC. Prescription labels of combination products with acetaminophen can be very confusing for the patient. For example, hydrocodone 10/650 has 650 mg of acetaminophen, but many patients would not know how to interpret that.

Grissinger reminded the audience that acetaminophen can be toxic, even though it is sold OTC. A recent study showed that acetaminophen-induced liver toxicity accounts for more than 40% of US cases of acute liver failure.[7]

Antibiotics are the next big group of drugs associated with medication errors. As with opioids, the liquid dose concentrations increase the risk for mistakes. Confusion over measurements in "mL" vs "tsp" (teaspoons) can cause a 5-fold overdose or underdose if undetected. In one case, for example, azithromycin suspension was dispensed with directions to take 2.5 tsp daily (equivalent to 12.5 mL) instead of the intended 2.5 mL daily, Grissinger reported. The entire contents of the bottle were administered according to the labeled instructions, and the child developed diarrhea.

Reconstituting antibiotics can also be problematic. Pharmacists have mistakenly reconstituted antibiotic suspensions with alcohol instead of distilled water.

System Errors May Interfere With Individual Efforts

Most healthcare professionals have learned the "5 rights" of safe medication use: the right patient, the right drug, the right time, the right dose, and the right route of administration.
However, in his book Medication Errors, Michael Cohen wrote that these "rights" focus on individual performance and can overlook system errors. Examples of system errors are poor lighting, inadequate staffing, handwritten orders, doses with trailing zeros, and ambiguous drug labels. All of these can prevent healthcare professionals from verifying the 5 rights.[8]

Experts at ISMP have identified 10 key "system" elements that most influence medication use, reported Donna Horn, RPh, DPh, ISMP Director, Patient Safety - Community Pharmacy. Systems factors play a major role in increasing the likelihood that an individual will make an error. Deficiencies in any of these system elements can lead to medication errors[9]:

Patient information (age, weight, allergies, diagnoses, and pregnancy status);
Drug information (up-to-date information readily available);
Communication (collaborative teamwork between all healthcare members and the patient);
Drug labeling, packaging, and nomenclature (limit look-alike and sound-alike drug names, confusing packaging);
Drug standardization, storage, and distribution (restricting access to high-alert drugs);
Medication delivery device acquisition, use, and monitoring;
Environmental factors (poor lighting, cluttered work spaces, noise, interruptions, nonstop activity, and deficient staffing);
Staff competency and education;
Patient education; and
Quality processes and risk management (systems are needed for identifying, reporting, analyzing, and reducing the risk for medication errors with a nonpunitive culture of safety).

When an error occurs, it is tempting to blame individuals, Horn said. A "systems approach," however, looks at the whole system rather than individual errors. For instance, failures in the design or implementation of systems can lead to excessive reliance on memory, lack of standardization, inadequate access to information, and poor work schedules. Thus, with a systems approach, accountability is expanded to include anyone who had any influence over the error, setting the stage for broader solutions.

How Can We Prevent Medication Errors?

Nearly half of all adverse drug events have some form of "preventability," and many do not represent errors of commission but, rather, errors of omission. This implies a failure on the part of someone (pharmacist, physician, patient, or the interactions between these groups) to detect certain factors that most likely led to the adverse event. These factors include:

Failure to detect a disease state contraindication to the drug therapy;
Failure to detect a significant drug interaction;
Failure to detect a significant drug allergy;
Failure to prescribe the correct dose for a specific patient;
Failure to monitor drugs with narrow therapeutic indexes; and
Patient knowledge deficits.

Many of these can be avoided by spending a few minutes counseling the prescriber and/or the patient. Communication is key, Horn said. Barriers to effective communication include illegible handwriting, abbreviations, verbal orders, ambiguous orders, and fax or ePrescribing problems.
When communicating with prescribers, pharmacists should identify the issues clearly and concisely, said Marialice Bennett, RPh, FAPhA, Professor and Pharmacy Director of the University Health Connection at Ohio State University in Columbus, Ohio.[10] She offered these suggestions for such discussions:

Outline the specifics of the problem;
Keep focused on the patient;
Provide possible solutions;
Ask for prescriber feedback; and
Document the final decision.

Conflict can lead to poor communication, which can hinder the discovery of medication errors, she said. Conflicting opinions about patient care should be handled objectively and professionally. The ISMP recommends that healthcare organizations create a code of conduct that encourages behaviors supportive of team cohesion, staff morale, and sense of self-worth and safety.

Managing Stress in a Workplace Full of Risks

Pharmacy work can be highly stressful, and pharmacists who are under extreme stress are at risk for more errors, said Henry Cobb, PhD, MD, BS, CDM, Clinical Associate Professor, University of Georgia College of Pharmacy, Athens, Georgia.[11] Pharmacists need to identify their own personal stress triggers and anticipate their responses to stress. He presented 5 questions that could be used for such self-analysis:

How do you know whether stress is a problem for you?
What is causing most of your stress?
Is your supervisor aware of the problem?
How do you deal with stress?
What can you do to reduce the impact of stress?

Cobb described 3 ways that most workers deal with stress on the job. The active-cognitive person draws on past experience, taking one thing at a time. He or she considers several alternatives, looking for the positive side, and is able to step back and be objective. The active-behavioral person finds out more about the situation and takes positive action. He or she may talk with a friend or spouse, exercise more, or talk with a professional in order to find a solution. The person who practices avoidance keeps feelings to himself or herself, prepares for the worst, takes out frustrations on others, and eats or smokes more to reduce tension.

Identifying the phases of stress can be helpful. Phase 1, or the warning phase, includes vague anxiety, depression, and apathy. Phase 2, or mild stress, includes sleep disturbances, muscle aches, and irritability. Entrenched stress, or phase 3, includes alcohol abuse, depression, ulcers, withdrawal, and marital discord. Phase 4, or severe stress, includes asthma, heart problems, severe depression, violence (or suicide), paranoia, and uncontrolled anger. It is important to note that professional help is needed for phases 3 and 4.

To reduce stress on the job, Cobb presented this list of quick strategies:

Discontinue caffeine;
Engage in regular exercise (30 minutes 3 times weekly);
Practice relaxation-breathing exercises (20 minutes 2 times weekly);
Get adequate sleep (try going to bed 30 minutes earlier than usual);
Nurture your leisure time, engage in hobbies;
Set realistic expectations and avoid perfection;
Reframe your outlook to be optimistic, not pessimistic;
Eat right;
Maintain a sense of humor;
Talk and vent;
Write down your thoughts;
Avoid unhealthy habits (such as alcohol);
Set limits (learn to say "no"); and
Get help from a professional.

In some cases, however, a person who is in a job that does not match his or her personality and preferences may need to switch to another role or job, Cobb added. That may be a much better stress-reduction technique than any other.

References
References
Three examples below. -->
Kohn K, Corrigan JM, Donaldson MS. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy of Sciences, National Academy Press; 2000.

Committee on Identifying and Preventing Medication Errors. Board on Health Care Services. Institute of Medicine of the National Academies. In: Aspden P, Wolcott J, Bootman JL, Cronenwett LR, eds. Preventing Medication Errors: Quality Chasm Series. Washington, DC: The National Academies Press; 2006.

Grissinger M. Top 10 adverse drug reactions and medication errors. Program and abstracts of the American Pharmacists Association 2007 Annual Meeting; March 16-19, 2007; Atlanta, Georgia.

Budnitz DS, Pollock DA, Weidenbach KN, Mendelsohn AB, Schroeder TJ, Annest JL. National surveillance of emergency department visits for outpatient adverse drug events. JAMA. 2006;296:1858-1866.

United States Pharmacopeia Web site. Available at: http://www.usp.org/ Accessed April 27, 2007.

Institute for Safe Medication Practices (ISMP). ISMP action agenda: Oct-Dec 1998. ISMP Medication Safety Alert! Available at: http://www.ismp.org/Newsletters/default.asp Accessed April 1, 2007.

Larson AM, Polson J, Fontana RJ, et al; Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364-1372.

Cohen M, ed. Medication Errors. 2nd ed. Washington, DC: American Pharmacists Association; 2007:5-36.

Horn D. Top 10 adverse drug reactions and medication errors. Program and abstracts of the American Pharmacists Association 2007 Annual Meeting; March 16-19, 2007; Atlanta, Georgia.
Bennett M. Communicating drug therapy recommendations to prescribers. Program and abstracts of the American Pharmacists Association 2007 Annual Meeting; March 16-19, 2007; Atlanta, Georgia.

Cobb H. Dealing with stress: decompression strategies for pharmacists. Program and abstracts of the American Pharmacists Association 2007 Annual Meeting; March 16-19, 2007; Atlanta, Georgia.

2007-06-10T09:06:00.000-07:00

Health-Related Quality of Life and Weight Loss Practices Among Overweight and Obese US Adults, 2003 Behavioral Risk Factor Surveillance System

Posted 05/14/2007
Source: http://www.medscape.com/viewarticle/555511?src=mp

Connie L. Bish, PhD; Heidi Michels Blanck, PhD; L. Michele Maynard, PhD; Mary K. Serdula, MD; Nancy J. Thompson, PhD; Laura Kettel Khan, PhD
Author Information

Abstract
Background: Trying to lose weight is a concern for many Americans, but motivation for weight loss is not fully understood. Clinical assessment for obesity treatment is primarily based on measures of body size and physical comorbidities; however, these factors may not be enough to motivate individuals to lose weight. Health-related quality of life (HRQOL) may have a role in an individual's decision to try to lose weight. The objective of this study was to examine the prevalence and association of HRQOL measures as independent moderators of weight loss practices among overweight and obese men and women.

Research Methods and Procedures:
Data were from the 2003 Behavioral Risk Factor Surveillance System, an annual state-based telephone survey of the civilian noninstitutionalized population of adults 20 years of age or older with BMI ≥ 25.0 kg/m2 (n = 111,456) who responded to 4 standard HRQOL measures that assessed general health status, physical health, mental health, and activity limitation in the past 30 days.

Results:
Among men with BMI 25-34.9 kg/m2, the odds of trying to lose weight increased for the moderate vs best category of HRQOL but not for the poorest vs best category, and no associations were noted for men with BMI ≥ 35 kg/m2. Women with BMI 25-34.9 kg/m2 had reduced odds and decreasing associated trends in the prevalence of trying to lose weight with poorer general health, increased physically unhealthy days, and increased activity limitation days. Conversely, women with 1-13 vs 0 mentally unhealthy days had greater odds of trying to lose weight. Among those trying to lose weight, reducing calories was common (52%-69%, men; 56%-69%, women). Among men, with the exception of recent mental health, poorer levels of HRQOL measures were associated with diminished attainment of recommended physical activity levels. Among women, poorer general health status was associated with diminished attainment of recommended physical activity levels.

Discussion:
With the exception of recent mental health, HRQOL was differentially associated with trying to lose weight among men and women. Specifically, moderately poor HRQOL among men and better HRQOL among women were associated with trying to lose weight. Consideration of these influences on weight loss may be useful in the treatment and support of obese patients.

2007-06-10T09:04:00.000-07:00

Even Small Amounts of Exercise Are Beneficial

from Heartwire — a professional news service of WebMD

May 17, 2007 — Even small amounts of physical activity — approximately 75 minutes per week — can improve cardiorespiratory fitness levels of sedentary overweight individuals, a study shows.

While this level of exercise is lower than that currently recommended to produce weight loss, the current findings may be used to encourage those people who do not exercise at present to start doing some form of physical activity, the authors advise.

The study, published in the May 16 issue of JAMA, was conducted by a team led by Timothy S. Church, MD, MPH, PhD, from the Louisiana State University System in Baton Rouge.

The authors point out that improvements in fitness are associated with a reduction in the risk for cardiovascular disease and death, and that, as physical activity is the main determinant of fitness in adults, continuing to refine efficient, safe, and acceptable exercise regimens is of substantial public health importance. Whereas the National Institutes of Health (NIH) Consensus Development Panel recommends at least 30 minutes of moderate-intensity physical activity on most days of the week, the authors note that recent reports suggest that 60 minutes of exercise each day may be necessary to prevent weight gain. But they add that the effect of much lower amounts of exercise has not been well studied.

The team therefore conducted a trial in which 464 sedentary postmenopausal women who were overweight or obese and had raised blood pressure were randomized to 3 different durations of moderate exercise (cycling or walking) or to a nonexercise control group for 6 months. The 3 exercise levels were designed to achieve energy expenditure of 4 kcal/kg (400 calories), 8 kcal/kg (800 calories), or 12 kcal/kg (1200 calories) per week, which corresponded to 50%, 100%, and 150% of NIH-recommended exercise levels. Aerobic fitness was assessed on a cycle ergometer and quantified as peak absolute oxygen consumption. Results showed a graded increase in fitness levels with increased exercise levels.

Table. Relationship Between Exercise Time and Fitness Level
Parameters
Weekly Energy Expenditure, kcal/kg
4
8
12
Exercise time per week, minutes
72.2
135.8
191.7
Change in peak absolute oxygen consumption vs control, %
4.2
6.0
8.2
Source: JAMA. 2007;297:2081-2091.

Church and colleagues report that these improvements in fitness occurred at a modest training intensity and during a time of life when fitness is decreasing at 1% to 2% per year. They also point out that the adherence rate was high and dropout rate was low, suggesting that the exercise regimens followed in this study were realistic and achievable. In addition, they found that the physical activity–fitness dose response relation to be similar across age, race, weight, baseline fitness, and hormone therapy subgroups.

Although the changes in fitness shown in this study were not accompanied by a reduction in blood pressure, weight, or most other cardiovascular risk factors, those who exercised did show a decrease in waist circumference, which the authors say is important given the increased risk for insulin resistance, diabetes, metabolic syndrome, and mortality associated with excess abdominal fat.

"Perhaps the most striking finding of our study is that even activity at the 4-kcal/kg per week level (approximately 72 min/wk) was associated with a significant improvement in fitness compared with women in the nonexercise control group," the authors write.

They note that nearly everyone understands that there are health benefits associated with physical activity, yet still about 20% of US adults do not engage in any physical activity at all. "Data presented in our study show that even 72 minutes of moderate-intensity physical activity per week accumulated over about 3 days has a significant effect on fitness in previously sedentary postmenopausal women. This information can be used to support future recommendations and should be encouraging to sedentary adults who find it difficult to find the time for 150 minutes of activity per week, let alone 60 minutes per day," they add.

How Much Exercise Do We Need?

In an accompanying editorial, I-Min Lee, MBBS, ScD, from Brigham and Women's Hospital in Boston, Massachusetts, explains that guidelines on how much exercise should be done have varied, with recommendations from the 1970s and 1980s prescribing vigorous exercise (eg, running) for 20 minutes continuously, 3 days per week; those from the 1990s suggesting at least 30 minutes per day of accumulated moderate-intensity activity (eg, brisk walking) most days of the week; and most recent reports advocating at least 60 minutes per day of moderate activity. "Predictably, many patients and clinicians are confused about what dose of physical activity is needed," she writes, adding that the current study provides some clarification on the dose-response issue.

But she adds that overweight individuals should not be lulled into believing that 72 minutes per week of physical activity will ameliorate their weight concerns and that, given the typical US diet, guidelines suggesting 60 minutes or more of daily physical activity are more appropriate if weight control is the primary goal.

The editorialist also points out that many questions remain unanswered. These include whether vigorous activities, such as running, can improve the cardiovascular risk factors that the moderate activities in the current study did not, whether a different pattern of moderate exercise would show the same fitness gain, and what the highest advisable level of exercise is.

Even a Little Is Good; More May Be Better

But Dr. Lee concludes, "Although current knowledge regarding the dose-response relation between physical activity and health remains incomplete, the study by Church et al does provide important information on the dose of physical activity to improve physical fitness, a strong predictor of chronic disease and premature mortality. This may be succinctly summarized for patients and clinicians as 'Even a little is good; more may be better!'"

JAMA. 2007;297:2053, 2081-2091.

2007-06-10T09:02:00.000-07:00

Low–Glycemic-Load Diet Better Than Low-Fat Diet for Weight Loss in Those With High Insulin Secretions

from Heartwire — a professional news service of WebMD

May 16, 2007 — Individual differences in insulin secretion may explain why some individuals respond well to either a low-fat diet or low–glycemic-load diet, whereas others do not, a randomized study suggests. The findings imply that a simple, baseline oral glucose tolerance test to assess serum insulin concentration may help clinicians and dieticians choose weight-loss strategies for obese subjects.

Cara B. Ebbeling, PhD, from Children's Hospital Boston, in Massachusetts, and colleagues, report the results of their study in the May 16 issue of JAMA.

"We often ask, why do people succeed with a conventional low-fat diet while others who are following the exact same diet can't keep weight off?" Dr. Ebbeling told heartwire. "Usually we answer this question with something like: 'the ones who succeed are more motivated, or have more willpower, or they're more able to stick with a diet while others are not as motivated.' But this really is not a complete answer to the question. So we sought to determine if biology had something to do with it."

Diet Success

Ebbeling and colleagues randomized 73 obese young adults (aged 18 - 35 years) to a 6-month dietary intervention: either a low–glycemic-load diet (40% carbohydrate, 35% fat, and rich in low–glycemic index foods), or a low-fat diet (55% carbohydrate and 20% fat). At baseline, all subjects were given an oral glucose tolerance test to check for insulin concentration after 75 g of dextrose. Subjects adhered "intensively" to diets for 6 months, then were followed up for an additional 12 months.

For the group as a whole, changes in body weight and body fat percentage at 18 months did not differ between the 2 diet groups; however, when stratified according to baseline glucose tolerance test, subjects with above-median insulin concentration (> 57.5 µlU/mL) lost significantly more weight on the low–glycemic-load diet than they did on the low-fat diet by 18 months. In contrast, subjects with insulin concentrations below median levels (≤ 57.5 µlU/mL) during the baseline glucose tolerance test had similar outcomes, regardless of to which diet they had been randomized.

Table 1. Changes by Diet After 18 Months, Above Median Insulin Concentration Subjects
Outcome
Low–Glycemic-Load Diet
Low-Fat Diet
P
Weight change, kg
-5.8
-1.2
.004
Body fat, %
-2.6
-0.9
.03

Source: JAMA. 2007;297:2092-2102.

Differences between the diets were seen in effects of the different diets on lipid parameters, regardless of baseline glucose tolerance tests. The low–glycemic-load diet produced significant improvements in high-density lipoprotein (HDL) cholesterol and triglyceride profiles, whereas the low-fat diet produced significantly greater reductions in low-density lipoprotein (LDL) cholesterol levels.

"Regardless of insulin secretion at baseline, the LGL [low–glycemic-load] diet has beneficial effects on HDL cholesterol and triglycerides that were not seen on the LF [low-fat] diet, while LDL cholesterol decreased in the participants in the LF diet, but not the LGL diet," Dr. Ebbeling said. "This is just is speculation on our part, but an LGL diet that also substitutes unsaturated fats for fats may be even more beneficial for everyone, since the beneficial effects on insulin, cholesterol, and triglycerides with the LGL diet were seen regardless of insulin secretion."

Table 2. Lipid Changes by Diet, Entire Cohort*

Parameter
Low–Glycemic-Load Diet
Low-Fat Diet
P
LDL, mg/dL
-5.8
-16.3
.03
HDL, mg/dL
1.6
-4.4
.002
Triglycerides, %†
-21.2
-4.0
.02
*LDL indicates low-density lipoprotein cholesterol; HDL, high-density lipoprotein cholesterol.†mg/dL measurements log-transformed to percentages to reduce skew.

Source: JAMA. 2007;297:2092-2102.

Spikes in insulin concentration after a meal are believed to promote feelings of hunger and can lead to overeating, Dr. Ebbeling told heartwire. "People who are 'high insulin secreters' may be particularly susceptible to weight gain with conventional low fat diets that are higher in carbohydrates." By contrast, low insulin secreters seem to do the same on either the low-fat diet or the low–glycemic-load diet, she continued. "It seems that people who are high insulin secreters may be particularly susceptible to weight gain and may be more challenged to lose weight with a conventional low fat diet."

Of note, in survey questions assessing levels of satisfaction with the diets or with degree of weight loss, or probing ease or palatability of the diets, study subjects responded similarly to both questions.

"From a clinical perspective, our findings provide rationale for individualizing weight loss diets or diet prescription based on an oral glucose tolerance test," Dr. Ebbeling told heartwire.

JAMA. 2007;297:2092-2102.

2007-06-10T09:00:00.000-07:00

Fiber and Magnesium Intake Protects Against Developing Type 2 Diabetes

Arch Intern Med. 2007;167:956-965.

May 14, 2007 — Higher cereal fiber and magnesium intake may decrease risk for type 2 diabetes, according to the results of a prospective cohort study reported in the May 14 issue of the Archives of Internal Medicine.

"Prospective studies on fiber and magnesium intake and risk of type 2 diabetes mellitus were inconsistent," write Matthias B. Schulze, DrPH, from the German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, and colleagues. "Current guidelines for the prevention of type 2 diabetes by the American Diabetes Association and the European Association for the Study of Diabetes include goals for total dietary fiber intake. It has been suggested that the benefits of increased fiber intake result principally from the greater consumption of soluble forms due to effects on gastric emptying, macronutrient absorption, and reduced postprandial glucose responses."

The objective of this study was to evaluate the association between total, cereal, fruit, and vegetable fiber, as well as soluble and insoluble fiber and magnesium intake, and risk of type 2 diabetes in a large prospective cohort study of men and women. Also, the study summarized the existing evidence from prospective studies by meta-analysis.

From 1994 to 2005, investigators in the European Prospective Investigation Into Cancer and Nutrition–Potsdam study observed 9702 men and 15,365 women for the development of incident diabetes. Participant age at study entry was 35 to 65 years. A validated food-frequency questionnaire (FFQ) was used to estimate dietary intake of fiber and magnesium.

For the meta-analysis, the investigators searched PubMed through May 2006 for prospective cohort studies of fiber and magnesium intake and risk of type 2 diabetes and identified 9 cohort studies of fiber and 8 studies of magnesium intake. A random-effects model was used to calculate summary relative risks (RRs).

During 176,117 person-years of follow-up, there were 844 incident cases of type 2 diabetes. Higher cereal fiber intake was inversely associated with diabetes risk (RR for extreme quintiles, 0.72 [95% confidence interval [CI], 0.56 - 0.93]). However, no significant associations were observed for fruit fiber (0.89 [95% CI, 0.70 - 1.13]) and vegetable fiber (0.93 [95% CI, 0.74 - 1.17]).

The meta-analyses revealed a lower diabetes risk with increased intake of cereal fiber (RR for extreme categories, 0.67 [95% CI, 0.62 - 0.72]), but no significant associations for fruit (0.96 [95% CI, 0.88 - 1.04]) and vegetable fiber (1.04 [95% CI, 0.94 - 1.15]).

In the European Prospective Investigation Into Cancer and Nutrition–Potsdam study, magnesium intake was not related to diabetes risk (RR for extreme quintiles, 0.99 [95% CI, 0.78 - 1.26]). However, meta-analysis revealed a significant inverse association (RR for extreme categories, 0.77 [95% CI, 0.72 - 0.84]).

Study limitations include inability to address whether the association between fiber and magnesium intake and diabetes risk is independent of or may be modified by the glycemic index; potential residual confounding; possible change in dietary intake after the baseline measurement; and reliance on FFQs.

"Higher cereal fiber and magnesium intakes may decrease diabetes risk," the authors write. "Whole-grain foods are therefore important in diabetes prevention."

The Federal Ministry of Science, Germany; the European Union; German Cancer Aid; and the European Community supported this study. The authors have disclosed no relevant financial relationships.

2007-06-10T08:59:00.000-07:00

Diabetes Drug Costs Could Soar 70 Pct by '09: Report

By Bill Berkrot

NEW YORK (Reuters) May 17 - A growing diabetes epidemic and more aggressive treatment with combination drug therapies could result in a rise of nearly 70% in drug spending on the disease through 2009, according to a report released on Thursday by Medco Health Solutions Inc.

Medco's 2007 Drug Trend Report found diabetes treatments trailing only cholesterol medications in total prescription drug spending growth in 2006.

"There are going to be a lot more drugs coming out and more and more people with type 2 diabetes will catapult diabetes to the number one class in driving year over year spending growth," Dr. Lon Castle, director of medical policy for Medco, said in an interview.

The analysis projects that, by 2009, spending on medicines to treat diabetes could soar by 60% to 68% from 2006 levels.

Spending on diabetes treatments increased 14.5% from 2005 to 2006 and the use of diabetes drugs increased 5.1%. The U.S. sales of diabetes drugs reached $9.88 billion in 2005, according to data from IMS Health Inc.

An aging population and the alarming rise in obesity -- a leading cause of diabetes -- are expected to push spending growth rates on diabetes drugs up 16% to 20% annually.
Use is expected to increase by 8% to 10% each year, with patients more frequently using new drug combinations to reach target blood sugar levels, the Medco analysis of likely future prescription drug spending and utilization found.

A wave of new diabetes treatments, such as Merck & Co.'s, Januvia, and Byetta from Eli Lilly and Co. and Amylin Pharmaceuticals Inc., and others expected to hit the market from the likes of Novartis AG and Novo Nordisk A/S, will help push up treatment costs, the report said.

Some newer drugs that act on new targets are increasingly being prescribed as first-line therapy and are frequently being used in combination with other drugs, driving up costs this year and going forward, the report said.

Use of lower cost generic drugs could mitigate pricing pressures, said Medco, a pharmacy benefits manager that negotiates prescription drug costs for companies and other large clients.

But while new medicines and combination therapies can be expensive, the cost of treating complications from untreated diabetes would create a much larger burden on government and private health plans and patient pocketbooks.

2007-06-10T08:57:00.000-07:00

Continuous Glucose Monitor System Is Consistent and Accurate

Reuters Health Information 2007.
By Karla Gale

NEW YORK (Reuters Health) May 11 - A new instrument to continuously monitor glucose levels, the FreeStyle Navigator (Abbott Diabetes Care, Alameda, CA), does well when compared with venous blood samples measured with a conventional clinical laboratory glucose analyzer, according to results of a multicenter, prospective trial report.

"Perhaps more important is that the accuracy was well sustained when the study was performed as real, day-to-day living experiences," lead author Dr. Richard L. Weinstein, president and medical director of Diablo Clinical Research in Walnut Creek, California, told Reuters Health. "We used challenges with insulin and glucose to simulate normal variation associated with food intake, oral medications, insulin and physical intake."

The findings from his group's experiments with the FreeStyle Navigator appear in the May issue of Diabetes Care.

The investigators describe The FreeStyle Navigator, which consists of a miniature electrochemical sensor placed into subcutaneous adipose tissue, usually on the lateral or posterior upper arm, to measure glucose concentration in the interstitial fluid. A radiofrequency sensor/transmitter that connects to the sensor is placed in the abdomen, and a hand-held receiver uses the sensor signals to display continuous glucose values.

For the current study, 58 adult subjects with type 1 diabetes stayed at the clinic for 5 days. On day 1, they were implanted with both sensors. The sensors were calibrated using capillary fingerstick blood at 10, 12, 24, and 72 hours after insertion.

During the trial, venous samples were taken every 15 minutes in two or three separate sessions. Participant were also given an insulin challenge and an oral glucose load at different times to obtain readings during rapidly falling and rising blood glucose levels.

Compared with venous samples, the FreeStyle Navigator was able to provide an audible alarm and accurately detect hypoglycemia in 96% of cases and hyperglycemia in 99.7%.

"The fact that the accuracy data are robust and statistically significant, combined with the use of trend arrows, and both a projected and threshold alarm system," will help patients' efforts to tightly control their blood glucose levels, Dr. Weinstein said.

Even though the study was conducted in subjects with type 1 diabetes, Dr. Weinstein believes that the monitor will also help type 2 diabetics who require insulin to gain control over glucose level excursions, thereby preventing or postponing many of the cardiovascular and neuropathic consequences of poor glucose control.

The FreeStyle Navigator is "under review" by the US Food and drug Administration.

Diabetes Care 2007;30:1125-1130.

2007-05-13T17:43:00.000-07:00

Collaboration Identifies New Genes Associated With Risk of Type 2 Diabetes Mellitus

Michael O'Riordan
Heartwire 2007

May 2, 2007 (Ann Arbor, MI) – A large collaboration of researchers from Europe and the US has identified at least four new genetic variants associated with an increased risk of type 2 diabetes mellitus [1].

The four newly identified genes--CDKN2A, CDKN2B, both lying on chromosome 9; IGF2BP2, which lies on chromosome 3; and CDKAL1--were identified through a genomewide association study, an analysis that allows investigators to scan thousands of individuals' genomes to identify single nucleotide polymorphisms (SNPs). The international team also confirmed previous findings that six other genetic variants--TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, and FTO--are associated with an increased risk of developing diabetes.

"While large samples and collaboration between three groups were required, we can confidently state that new diabetes risk factors have been identified," write lead author Dr Laura Scott (University of Michigan, Ann Arbor) and colleagues in the in the April 26, 2007 issue of Science. "Each gene discovery points to a pathway that contributes to pathogenesis, and all of these proteins and their relevant pathways represent potential drug targets for the prevention or treatment of diabetes."

The findings emerge from the work of the Diabetes Genetics Initiative (DGI), a public-private partnership established in 2004 between the Broad Institute of Harvard University and Massachusetts Institute of Technology, Lund University in Finland, and Novartis. Investigators from the Wellcome Trust Case Control Consortium/UK Type 2 Diabetes Genetics Consortium and the National Human Genome Research Institute, a branch of the National Institutes of Health, also participated in the study.

Genome-wide association study

First-degree relatives of those with diabetes mellitus are at 3.5 times higher risk of developing diabetes than the general population, but to date identifying genetic risk factors in diabetes has met with limited success. To further define the "genetic architecture" of the disease and identify biological pathways involved in disease pathogenesis, the investigators genotyped 1161 Finnish patients with type 2 diabetes mellitus and 1174 Finnish subjects with normal glucose tolerance who participated in the Finland-United States Investigation of NIDDN Genetics (FUSION) and national FINRISK studies.

After carrying out an association analysis of the SNPs, investigators identified and confirmed three novel regions of the genome that influence the risk of type 2 diabetes. The three variations are located near genes believed to regulate insulin and those thought responsible for the growth of cells in the pancreas that produce insulin. In addition to identifying CDKN2A/CDKN2B, IGF2BP2, and CDKAL1, investigators also identified a region of chromosome 11 not previously known to contain any of the annotated genes.

These results were then replicated in two independent samples, first from the Wellcome Case Control Consortium and the second from genome scans of Swedish and Finnish participants in the DGI. The previously identified variants--TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11 and FTO--were also confirmed by investigators, boosting to 10 the number of genetic variants that are believed to play a role in the development of diabetes.

The researchers then scanned the genome of the Finnish participants for all 10 diabetes-associated genetic variants and constructed a logistic regression model to predict diabetes risk for each person. In doing so, they identified a subset of individuals with up to a four-times-higher risk of developing the disease, a finding with "potential interest for a personalized preventive medicine program," the group writes.

Inflammatory genes involved in cognitive decline after surgery

In a separate study published this week, investigators report on a potential genetic basis for cognitive decline following cardiac surgery [2]. Variants of two genes involved in the inflammatory process--CRP1059C and SELP1087A--provide protection against cognitive decline following surgery, report researchers.

Functionally, write lead author Dr Joseph Mathew (Duke University Medical Center, Durham, NC) and colleagues in the May 1, 2007 issue of the Journal of the American College of Cardiology, perioperative serum C-reactive protein (CRP) levels and the degree of platelet activation were also significantly lower in patients with these genetic variants, a finding that suggests it might be possible to identify patients who might benefit from perioperative anti-inflammatory strategies.

With measurable cognitive decline a problem in a large percentage of patients who undergo CABG surgery, investigators wanted to determine whether genetic polymorphisms regulating inflammation, cell-matrix adhesion/interaction, coagulation, lipid metabolism, or vascular reactivity might play a role in that decline. To do so, the Duke researchers selected a panel of 37 genes that previous studies had implicated in various impairments of cognitive and mental function.

In 513 patients, two variants involved in inflammation were identified in patients who had a significantly lower risk of postoperative cognitive decline. Patients with a CRP1059C allele were 20.6% less likely to suffer cognitive decline, and patients with the SELP1087A allele had a 15.2% risk reduction. The incidence of cognitive deficit in patients with both gene variants was 17% compared with 43% in patients who had neither variant, report investigators.

Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007;DOI: 10.1126/science.1142382. Available at: http://www.sciencemag.org.

Mathew JP, Podgoreanu MV, Grocott HP, et al. Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery. J Am Coll Cardiol 2007; 49:1934-42.

The complete contents of Heartwire, a professional news service of WebMD, can be found at www.theheart.org, a Web site for cardiovascular healthcare professionals.

2007-05-13T17:41:00.000-07:00

No Evidence of Decline in Cognitive Function With Intensive Diabetes Therapy

May 2, 2007 — Long-term follow-up data from the Diabetes Control and Complications Trial (DCCT), the landmark study that established the benefits of tight diabetes control in preventing complications in patients with type 1 diabetes, and its ongoing follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study now confirm that, despite more hypoglycemia and seizures in patients with type 1 diabetes given an intensive regimen, there is no evidence of a decline in cognitive function seen in these patients 18 years later.

The results are published in the May 3 issue of The New England Journal of Medicine.

"The findings of this study provide an important message about the safety of intensive diabetes therapy for those receiving a diagnosis of diabetes as adolescents or young adults," the group, with corresponding author Alan M. Jacobson, MD, from the Joslin Diabetes Center and Harvard Medical School in Boston, Massachusetts, writes.

Although acute hypoglycemic events can be dangerous at the time they occur, they note, "recurrent severe episodes associated with intensive diabetes therapy, as administered in the DCCT, do not appear to have long-term adverse effects on the cognitive capacity of patients with type 1 diabetes."

DCCT and EDIC Study

The increased risk for severe hypoglycemia from intensive diabetes treatment aimed at achieving blood glucose levels in the normal range remains one of the primary barriers to the implementation of this treatment, the authors note. The potential for cognitive consequences of severe hypoglycemia, including seizures and coma, are a key concern for clinicians, patients, and families, they write.

The DCCT was a multicenter randomized trial comparing intensive therapy using an insulin pump or with 3 or more daily insulin injections with conventional diabetes treatment consisting of 1 or 2 insulin injections per day in 1441 people with type 1 diabetes. The trial ran from 1983 to 1993, with an average follow-up of 6.5 years. Substantial reductions were seen in the development and progression of microvascular complications and in peripheral neuropathy with the intensive treatment.

The EDIC is an observational follow-up study including 1378 of the surviving DCCT participants. Follow-up in EDIC is now at 12 additional years and is funded to continue until 2016.

Previous data from EDIC proved that progression of retinopathy, nephropathy, neuropathy, and, more recently, cardiovascular events are all reduced by prior intensive therapy. However, it was clear from both phases of the study that intensive therapy increases the risk for hypoglycemic events ranging from mild to severe, defined as hypoglycemia resulting in coma or seizure.

Cognitive testing was incorporated into the DCCT to address concerns that these episodes would have an impact on cognitive ability. The current new analysis provides data on an additional 12 years of follow-up, for a total of 18 years. At the close of DCCT, all patients were switched to intensive management.

In the current analysis, 1144 patients who had undergone cognitive testing at enrollment to the DCCT and the same testing 18 years later were examined. Glycated hemoglobin levels were measured, and the frequency of severe hypoglycemic events leading to seizures or coma was recorded.

The researchers then assessed the effects of the original DCCT treatment assignment, mean glycated hemoglobin levels, and the frequency of hypoglycemic events on cognitive ability in these subjects. Adjustment was made for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss resulting from peripheral neuropathy, and the number of cognitive tests taken since the start of DCCT, to control for the effects of practice, they note.

Some 40% of the cohort reported having had at least 1 hypoglycemic coma or seizure.

Table

The Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study: Severe Hypoglycemic Events During 18 YearsEvents Intensive Treatment

(n = 588) Conventional Treatment
(n = 556)
Patients with no events 326 365
Patients with ≥ 1 event 262 191
Total events 896 459

Source: N Engl J Med. 2007;356:1842-1852.

Fifty-three deaths occurred during follow-up; 3 of these were attributed to hypoglycemia, all of which occurred during the EDIC follow-up.

However, neither frequency of severe hypoglycemia nor previous treatment assignment was associated with decline in any cognitive domain, the authors write. Higher glycated hemoglobin levels were associated with moderate declines in motor speed and psychomotor efficiency, suggesting some benefit of better glycemic control, but no other cognitive domain was affected.

"Our study found no evidence of substantial long-term declines in cognitive function in a large group of patients with type 1 diabetes who are carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia," the authors conclude.

"This conclusion lends further support to the use of intensive diabetes therapy to reduce the long-term risks of retinopathic, nephropathic, neuropathic, and cardiovascular complications in type 1 diabetes."

The study was supported by a grant from and contracts with the National Institute of Diabetes and Digestive and Kidney Diseases, and by the General Clinical Research Centers Program, National Center for Research Resources. Dr. Jacobson has disclosed serving on medical advisory boards for Pfizer and Amylin. Disclosure information for other authors is noted in the original article.

N Engl J Med. 2007;356:1842-1852.