Drug Fights Diabetic Eye Disease

October 4th, 2008

THURSDAY, Sept. 25 (HealthDay News) — New studies published this week in the The Lancet provide further evidence that candesartan, a blood pressure medicine, can cut the risk and severity of retinopathy in people who have diabetes.

“We suggest that clinicians may wish to consider using candesartan [brand name Atacand] in people with type 1 diabetes with hard-to-control blood glucose, who do not currently have retinopathy,” said one study’s British co-author, Dr. Nish Chaturvedi, of the National Heart and Lung Institute and Imperial College at St Mary’s, London. “In type 2 diabetes, in people with established retinopathy who become hypertensive, again the clinician may wish to consider candesartan from the many blood pressure-lowering agents available, as it appears to have this additional beneficial effect on regression of retinopathy.”
About 95 percent of diabetics suffer from type 2 diabetes, where cells gradually lose sensitivity to insulin. The illness is often linked to obesity. Around 5 percent of diabetics have the type 1 form, a condition in which the pancreas is unable to produce insulin to regulate blood sugar.Diabetic retinopathy is a potentially blinding illness linked to changes in retinal blood vessels. It is one of the major complications of both type 1 and type 2 diabetes. Intense control of blood sugar levels is the only proven way to reduce incidence and progression of retinopathy, but this kind of control can be elusive. And even when patients do achieve strict control of blood sugars, retinopathy is not always kept at bay.

Previous studies have indicated that drugs known as renin-angiotensin system blockers, which include candesartan, might prevent or reduce the severity of diabetic retinopathy.

This most current research consists of two trials, with three arms total.

In the DIRECT-Prevent 1 study, more than 1,400 type 1 diabetics with existing retinopathy were randomized to receive either Atacand or a placebo; in the DIRECT-Protect 1 trial, more than 1,900 type-1 diabetics with existing retinopathy were randomized to receive either the drug or a placebo.

Individuals receiving Atacand had an 18 percent lower incidence of retinopathy, considered “borderline” statistically significant, the researchers report.

Further analysis of the DIRECT-Protect 1 trial found that progression of retinopathy was 35 percent lower for patients taking Atacand.

Reanalyzing the data in this way somewhat weakens the findings, noted one expert, Dr. Mina Chung, a retinal specialist at the University of Rochester’s Eye Institute. Nevertheless, she added, “this study gives you some evidence that it looks like [Atacand] would be helpful.”

The DIRECT-Protect 2 study randomized more than 1,900 type 2 diabetes patients with mild to moderately severe retinopathy to either Atacand or a placebo.
Again, the difference in progression between the groups was statistically nonsignificant. Improvement increased by 34 percent in the Atacand group versus the placebo group.”Studies have shown that intensive control of blood-sugar levels helps prevent diabetic retinopathy, and now this is another component of the blood pressure effect, but it may also be additional benefits other than just controlling blood pressure,” said Dr. Richard W. Allinson, assistant professor of surgery with the Texas A&M Health Science Center College of Medicine and an ophthalmologist at the Scott & White Waco Clinic.

The trials were funded by AstraZeneca and Takeda. AstraZeneca markets Atacand under license from Takeda.

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Moderate Aerobic Exercise Lowers Diabetics’ Liver Fat

October 4th, 2008

THURSDAY, Sept. 25 (HealthDay News) — In people with type 2 diabetes, regular aerobic exercise and weightlifting may reduce levels of fat in the liver by as much as 40 percent, according to Johns Hopkins researchers.

High liver fat levels are common in type 2 diabetes patients and contribute to heart disease risk.

The study included 77 diabetic women and men who were divided into two groups. For six months, one group did three 45-minute sessions of moderate aerobic exercise (bicycling, running on a treadmill, or brisk walking) and three 20-minute sessions of weightlifting per week. The other group didn’t do any formal aerobic fitness or gym classes.
MRI scans showed that people in the exercise group had lower levels of liver fat by the end of the study (5.6 percent) than those in the non-exercise group (8.5 percent).

The exercise group also had better fitness and less body weight and fat than those in the non-exercise group. Those who did the aerobic/weightlifting program: had 13 percent higher averages for peak oxygen uptake levels during treadmill testing; were 7 percent stronger; had 6 percent lower body fat and body weight; and had 2-inch smaller waistlines (an average of 39 inches vs. 41 inches).

“The benefits in improved fitness and fatness are clear, and physicians should really have all people with type 2 diabetes actively engaged in an exercise program,” lead investigator Kerry Stewart, a professor of medicine and director of clinical and research exercise physiology at the Johns Hopkins School of Medicine and its Heart and Vascular Institute, said in a Hopkins news release.

The findings were presented Sept. 18 at the American Association of Cardiovascular and Pulmonary Rehabilitation annual meeting, in Indianapolis.

“People with type 2 diabetes have added reason to be active and to exercise, not just because it is good for health, but also because our study results pinpoint a key benefit to trimming the fatty liver that complicates their illness and which could accelerate heart disease and liver failure,” Stewart said.

About 14 million Americans have type 2 diabetes.

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New Diabetes Drug Works Well in Trial

October 4th, 2008

THURSDAY, Sept. 25 (HealthDay News) — One of a new class of diabetes drugs has done well in a trial conducted to help bring it to market, researchers report.

The drug, liraglutide, is a laboratory-made version of glucagon-like peptide-1 (GLP-1), a hormone produced by the body. Several members of the GLP-1 family are in clinical trials, and one already has been approved by the U.S. Food and Drug Administration.

In a phase 3 trial, usually the last kind done before marketing approval is sought, liraglutide had greater benefits against type 2 diabetes, the kind that generally develops in the adult years, than a now-standard medication, glimepiride, said a report in the Sept. 25 online issue of The Lancet.

Results of this trial and others have been given to the FDA, which will review them and decide whether to approve the drug for use in the United States, said trial leader Dr. Alan Garber, a professor of medicine, biochemistry and cell and molecular biology at Baylor College of Medicine, in Houston.

“It should be out sometime in the first half of next year,” Garber said.

Like the other GLP-1 versions, liraglutide has all the advantages of the natural molecule, with longer-lasting activity, said Dr. Sten Madsbad, a professor of endocrinology at the University of Copenhagen in Denmark, who wrote an accompanying editorial.

“First it stimulates insulin production,” Madsbad said. “Then it also promotes glucagon release from the pancreas. It also changes appetite, and therefore you eat less.”

Glucagon is a hormone that helps manages blood levels of sugar.

The trial was sponsored by the pharmaceutical company Novo Nordisk, which hopes to market the drug. If approved, liraglutide would be the second GLP-1 diabetes medicine on the U.S. market. The first is exenatide (Byetta), which was approved by the FDA in 2005. It is marketed by Amylin Pharmaceuticals and Eli Lilly. It is taken by injection twice a day, while liraglutide requires only one daily injection.

Exenatide is actually the form of GLP-1 found in the saliva of the gila monster, explained Dr. John Buse, president for medicine and science at the American Diabetes Association and a professor of medicine at the University of North Carolina. A new formulation of exenatide allowing once-a-week injection has successfully been tested, Buse added.

“There has been a lot of enthusiasm about exenatide based on reports of weight loss,” Buse said.

In a head-to-head test, liraglutide was more effective in controlling diabetes, Garber said. The newly reported study, he said, “shows that in patients already taking doses of existing oral medications, they did better when they switched to liraglutide.”

Weight loss was also seen in the trial, which ran for one year. Participants taking liraglutide lost an average of 4.4 pounds, while those taking glimepiride gained an average of 2.2 pounds.

“We want more medications that have this type of profile,” Garber said. “It is very well-tolerated, has few side effects and can lead to weight loss. Most diabetes medications now produce weight gain, and that is very discouraging to our patients.”

One shadow is a possible risk of pancreatitis, a condition which was reported in two people in the liraglutide trial and whose symptoms include nausea, vomiting and belly pain.

But Garber maintained that “there is unlikely to be a major pancreatitis concern, because it is so rare.”

A contest may develop between liraglutide and a once-a-week formulation of exenatide, Buse said. The longer-lasting exenatide version is expected to reach the U.S. market in about a year. It requires a standard hypodermic needle for injection, while liraglutide can be given through a small, ultrafine needle.

Several other GLP-1 drugs are in trials now and might be approved before long, Buse said. “It will be a great opportunity for patients to have so many choices,” he added.

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David Mendosa: Fatty Liver and Exercise

October 4th, 2008

If you read my articles about diabetes here regularly, you might have noticed that I rarely cover four topics in the news:

1. Knowing the causes of diabetes. This doesn’t help us control it.

2. Learning how to avoid diabetes. This comes too late for most of us.

3. Reading about great new drugs or treatments, This might have in a decade or so might help us some day — but not now.

4. Worrying about the possible complications of our diabetes. This would just add more negativity to our lives.

Of the 313 articles that I have written here about diabetes in the past three years, I did write 19 of them about complications. But each of them emphasized how to prevent or control one of these complications. That’s how I stay positive about the elephant in the room.

Today I am writing for the second time about one of these complications, fatty liver, and how to prevent it. I know how serious that liver disease can be. My wife, Catherine, who had type 2 diabetes, died one and one-half years ago of liver failure.

About 20 percent of the general U.S. population has nonalcoholic fatty liver disease. From 50 to 70 percent of people with type 2 diabetes have fatty liver. The difference in those proportions is enough to convince me that having a fatty liver is a complication of diabetes.

A couple of years ago my doctor thought that I might have fatty liver after I got some routine blood tests. Then, ultrasound confirmed it (since then, I have reversed this condition). That’s the way we usually learn that we have this complication.

Initially, we may not have any symptoms either from diabetes or fatty liver. That’s why both conditions are so insidious. No big deal, we may think.

But uncontrolled, fatty liver can lead to nonalcoholic steatohepatitis (NASH), which doctors sometimes call nonalcoholic fatty liver disease (NAFLD). That in turn can lead to cirrhosis of the liver.

Unless you can get a liver transplant, cirrhosis is fatal. Liver transplants may be available for people under 70 and my wife was only 69 when she died. But her doctor told her that her weight make a successful transplant unlikely, so she died.

Cirrhosis a well-known consequence of alcoholism. But more people die of nonalcoholic liver disease than from drinking too much. I know that my wife didn’t drink any alcohol.

Yet it turns out that fatty liver is among the complications of diabetes that submit to many different treatments. In my first article about fatty liver here almost two years ago I reviewed several of them.

Now, it appears that a little exercise can reverse the levels of fat in our liver by up to 40 percent. A moderate amount of exercise is all that it takes, according to a study by physical fitness experts at the Johns Hopkins University School of Medicine.

On Friday the researchers presented their findings at the annual meeting of the American Association of Cardiovascular and Pulmonary Rehabilitation. A Johns Hopkins spokesperson sent me the abstract of the study, “Exercise Training Reduces Hepatic Fat in Type 2 Diabetes: A Randomized, Controlled Trial” in Microsoft Word format. Since I couldn’t find it online anyplace else, I posted it on my site.

The researchers divided 77 men and women with diabetes into two groups and measured the liver fat of 44 of the participants.

Why only 44 of the 77 participants? I called Dr. Stewart at the annual meeting to find out.

“When we started the study, we didn’t plan to study hepatic fat,” he replied. “But after we started, some of my colleagues persuaded me to include it.”

Dr. Stewart says the team’s study is the first to specifically demonstrate the beneficial role that exercise plays in controlling hepatic fat levels in people with diabetes.

The researchers put half of the study participants through a moderate program of sustained aerobic exercise consisting of three weekly 45-minute sessions. The participants could bicycle, run on a treadmill, or take brisk walks. In addition, they lifted stacked weights for about 20 minutes, also three times a week — and not at a heavy-duty pace. They asked the other half of the participants to avoid any formal aerobic fitness or gym classes.

Special magnetic resonance imaging scans showed much lower levels of liver fat in the active group, which remained the same in the non-exercising group. The exercising group had 5.6 percent liver fat after six months. The non-exercising group had 8.5 percent.

Until Dr. Stewart and his team does more studies, we can’t tell how significant this is. He says his team’s next steps will be to analyze the long-term effect of moderate exercise on diabetes.

We already knew that exercise makes you feel and look better. It takes glucose out of your blood to use for energy. It helps prevent heart disease, depression, and even some forms of cancer. If you do enough, it will help you to lose weight.

But sadly, the link between exercise and fatty liver came too late for Catherine. It is timely for everyone else who has type 2 diabetes.

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Testosterone gel benefits some men with diabetes

August 26th, 2008

 

NEW YORK (Reuters Health) - 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).

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