MONDAY, Feb. 22 (HealthDay News) -- Excessive weight gain during pregnancy, especially the first trimester, may increase a woman's risk of gestational diabetes, say U.S. researchers.

Their three-year study included 345 pregnant women with gestational diabetes and 800 pregnant women without gestational diabetes, which is defined as glucose intolerance that typically occurs during the second or third trimester of pregnancy.

After the researchers adjusted for a number of factors -- age at delivery, previous births, pre-pregnancy body-mass index and race/ethnicity -- they found that women who gained more weight during pregnancy than recommended by the U.S. Institute of Medicine were 50 percent more likely to develop gestational diabetes, compared to those whose weight gain was within or below the IOM recommendations.

The link between pregnancy weight gain and gestational diabetes was strongest among overweight and non-white women.

The study was published online Feb. 22 in the journal Obstetrics & Gynecology.

"Health-care providers should talk to their patients early in their pregnancy about the appropriate gestational weight gain, especially during the first trimester, and help women monitor their weight gain. Our research shows that weight gain in early pregnancy is a modifiable risk factor for gestational diabetes," lead author Monique Hedderson, a scientist at the Kaiser Permanente Division of Research in California, said in a Kaiser news release.

Gestational diabetes -- which causes complications in as many as 7 percent of pregnancies in the United States -- can lead to early delivery, cesarean section and type 2 diabetes in the mother. It also increases the child's risk of developing diabetes and obesity later in life.

More information

The U.S. National Institute of Child Health and Human Development has more about gestational diabetes.

SATURDAY, Feb. 20 (HealthDay News) -- The blockbuster type 2 diabetes drug Avandia raises users' odds for heart attack and heart failure and should be removed from the market, according to confidential government reports.

The New York Times on Saturday reported on documents from the U.S. Food and Drug Administration that find that if people now taking Avandia (rosiglitazone) switched to a similar medication, Actos, about 500 heart attacks and 300 cases of heart failure would be eliminated each month. And in a report from the Institute for Safe Medication Practice, Avandia was linked to 304 deaths in the third quarter of 2009 alone, the highest for any prescribed drug in that time period, the Times reported.

In one of the FDA documents, dated October 2008, Drs. David Graham and Kate Gelperin -- drug safety officials at the agency -- agreed that "rosiglitazone should be removed from the market."

The reports, obtained early by the Times, are yet another chapter in Avandia's checkered history. The drug was once taken by millions worldwide, but that changed after a study released in early May of 2007 by the Cleveland Clinic suggested that Avandia carried cardiovascular risks. That study, which included more than 28,000 people, found that Avandia increased a user's odds of heart attack by 43 percent compared to those not taking the medicine.

At the time, Dr. Bruce M. Psaty of the University of Washington -- who also co-wrote an accompanying editorial in the New England Journal of Medicine -- urged the FDA to restrict access to Avandia and cited both the agency and the drug's maker, GlaxoSmithKline, for poor oversight.

"The primary problem here is that studies that were needed early on about the health benefits of this drug were never done," Psaty told HealthDay. "As a result of the failure of the sponsor to do long-term clinical trials to show health benefits, as a result of the failure of the FDA to insist on it, we have data that are weak."

Following on the Cleveland Clinic study, the FDA demanded "black box" warnings on labeling for both Avandia and Actos, warning of a potentially heightened risk for heart failure. However, other studies found no raised level of heart risk, and at the time the agency said it had not reached a definitive conclusion on the data.

In November of the same year, the FDA updated Avandia's labeling to include a caution regarding heart attack risk. At the time, Dr. Janet Woodcock, acting director of the FDA's Center for Drug Evaluation and Research, said that, "we are keeping Avandia on the market because we have concluded there isn't enough evidence to indicate that the risk of heart attack is higher for Avandia than other type 2 diabetes treatments."

The story got more complicated in 2008, as a number of studies emerged tying the use of Avandia to increased bone fracture risk.

Throughout 2009, more studies reiterating the drug's heart risks also came to light, including one published in the BMJ suggesting that Avandia's risk for heart failure seemed to outstrip those of its related rival, Actos.

By that point, "most clinicians [had] stopped using Avandia -- some will use Actos instead or go to another class completely," Dr. Carl J. Lavie, medical director of cardiac rehabilitation at the Ochsner Heart and Vascular Institute in New Orleans, told HealthDay at the time.

The emergence of the leaked documents on Saturday comes at a time when officials within the FDA seem to be at loggerheads over whether to ban Avandia or not, the Times reported. The newspaper said that some officials believe that safer alternatives exist, while others say the evidence on Avandia's safety is conflicted and the drug should remain available as a treatment option.

Trying to sort things out, in December of 2009 Woodcock asked officials at the FDA to convene another advisory committee to determine whether Avandia should remain on the market, with a decision expected this summer.

In the meantime, a bipartisan Senate investigation -- overseen by Sen. Max Baucus (D-Mont.) and Sen. Charles E. Grassley(R-Iowa) -- has pored over 250,00 internal documents from GlaxoSmithKline. The investigation has placed much of the blame for the Avandia debacle on the company, contending that it neglected to warn patients for years of the drug's dangers.

"G.S.K. executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk," according to the Senate investigation report, which is slated for release Monday but was obtained early by the Times.

Speaking to the newspaper Friday night, agency commissioner Dr. Margaret Hamburg said that, "I await the recommendations of the advisory committee. Meanwhile, I am reviewing the inquiry made by Senators Baucus and Grassley and I am reaching out to ensure that I have a complete understanding and awareness of all of the data and issues involved."

In a statement released Saturday, GlaxoSmithKline said it "rejects the conclusions about the safety of Avandia (rosiglitazone)" as reported in that day's Times story.

"Contrary to the assertions in the story, and consistent with the FDA-approved labeling, the scientific evidence simply does not establish that Avandia increases ischemic cardiovascular risk or causes myocardial ischemic events," the company said. "In 2007, the FDA considered all the available scientific evidence on Avandia, including Dr. Graham's assertions of elevated heart attack risk and demands that the product be withdrawn. Based on the scientific evidence and a recommendation by an independent advisory committee of experts convened by the FDA, the agency has ruled that Avandia remain available to patients for the treatment of Type 2 diabetes."

In the wake of the controversy, GlaxoSmithKline had been directed by the FDA to conduct a trial comparing rates of heart attacks, strokes and heart-linked deaths among users of Avandia, Actos or a placebo. But according to internal documents accessed by the Times, Graham and Gelperin characterized the study, called TIDE, as "unethical and exploitive," with patients being given Avandia despite the fact that it appears to come with greater risks and no added benefit over Actos.

One of the Graham/Gelperin reports -- dated October 2008 -- concludes that, "Although the proposed TIDE trial is motivated by a desire for definitive answers regarding the cardiovascular safety of the drug rosiglitazone, the safety of the study itself cannot be assured and is not acceptable."

However, other FDA officials overruled those concerns and TIDE is still enrolling patients, with preliminary results expected by 2014. Responding to the criticism, GlaxoSmithKline noted Saturday that, "TIDE has been approved by an independent review board and appropriate safety boards that are responsible for assessing the safety of conducting the trial."

The ongoing controversy has dampened patients' and physicians' enthusiasm for Avandia. According to the Times, while sales of the drug topped $3.2 billion in 2006, those numbers plummeted soon after the first studies suggesting risk emerged a year later.

Still, "hundreds of thousands" of people still take Avandia, the Times noted. GlaxoSmithKline's patent on the drug expires in 2012.

More information

Find out more about diabetes care at the American Diabetes Association  .

WEDNESDAY, Feb. 17 (HealthDay News) -- Bilberry extract helps control blood sugar levels in mice, researchers have found.

Bilberry and other brightly colored foods such as blueberries, purple grapes, cherries and cranberries contain anthocyanins, which are thought to reduce blood sugar, improve insulin sensitivity and reduce obesity in laboratory mice.

To study these effects further, Japanese researchers used mice genetically predisposed to develop diabetes. The mice were fed either a diet containing bilberry extract (27 grams per kilogram) or their normal diet for five weeks.

The study authors found that bilberry extract lowered blood glucose and increased insulin sensitivity in the mice. It did this by activating AMP-activated protein kinase (AMPK) in white adipose (fat) tissue, skeletal muscle and the liver, the researchers explained. AMPK stimulates fat breakdown in liver and muscle, and modulates insulin secretion by the pancreas.

The effect of AMPK was accompanied by an increase in glucose transporter 4 (which helps glucose enter cells) in white adipose tissue and skeletal muscle, and suppression of glucose production and fat content in the liver. At the same time, acetyl-CoA carboxylase (an enzyme needed for fatty acid synthesis) was inactivated and there was activation of PPARa (a protein that modulates fat metabolism), acyl-CoA oxidase (an enzyme that plays a role in fatty acid metabolism), and carnitine palmitoyltransferase-1A (an enzyme needed for the breakdown of fatty acids) in the liver.

This "overlapping and coordinated adjustment of enzymes and other factors" seen in the mice that were fed the bilberry extract might also occur in humans, the researchers said. They recommended that clinical studies be conducted to test the effects of bilberry on human health, especially in people at increased risk for type 2 diabetes.

The findings are published in the March issue of the Journal of Nutrition.

More information

The U.S. National Center for Complementary and Alternative Medicine has more about the bilberry.