A new study led by a federal drug safety expert ties the controversial diabetes drug Avandia to a higher risk of heart problems, strokes and deaths in older adults, and says it is more dangerous than a rival drug Actos.

The study, a huge review of Medicare records, comes two weeks ahead of a Food and Drug Administration hearing on Avandia’s safety. The lead author, Dr. David Graham, is an FDA scientist who wants the pill banned.

As many as 100,000 heart attacks, strokes, deaths and cases of heart failure may be due to Avandia since it came on the market in 1999, Graham said in an interview with The Associated Press.

Harms from Avandia are great enough to “put you in a hospital or in a cemetery,” he said.

Editors at the Journal of the American Medical Association rushed to release the study online on Monday, so the information would be available before the July 13-14 hearing, a spokeswoman said.

Avandia is a once-blockbuster drug for Type 2 diabetes, the most common form of the disease and the kind often tied to obesity. Avandia and Actos are pills that help the body make better use of insulin, a key digestive hormone.

The American Heart Association issued a statement reminding patients not to stop taking any medicine without talking with their doctors first. The new study is not definitive enough to prove harm but “deserves serious consideration” and should be discussed between patients and their doctors, the statement says.

Avandia has been under a cloud since May 2007, when a review of dozens of studies suggested it may raise the risk of heart attacks and heart-related deaths. Warnings were added to its label, and the American Diabetes Association told patients to avoid using it until safety questions were resolved.

The FDA and Congress have held meetings on the drug but it has remained on the market, still used by hundreds of thousands of Americans.

Avandia’s maker, the British company GlaxoSmithKline PLC, maintains that its drug is safe. A spokeswoman said the new study has limitations, and that the company looks forward to a full discussion of evidence at the FDA hearing.

The study involved 227,571 Medicare patients, average age 74, who started on Actos or Avandia from July 2006 through June 2009 and were followed for three years on average.

Avandia patients were 27 percent more likely to suffer strokes, 25 percent more likely to develop heart failure and 14 percent more likely to die than those on Actos, researchers found.

There were 2,593 heart attacks, heart failure cases, strokes and deaths among the 67,593 Avandia users, and 5,386 of those problems among the 159,978 people taking Actos. Just dividing these numbers to compare side effect rates can’t be done, though, because people were on the drugs for differing lengths of time.

Unlike studies in younger patients that implicated Avandia, heart attack risks were similar in both groups in the Medicare study. Sudden cardiac deaths are much more common in older adults, and whether Avandia affects heart risks differently in older versus younger patients is unknown, the researchers note.

The findings suggest that if 60 people were treated with Avandia for one year, one extra case of heart failure, stroke or death would occur that could have been avoided if they’d taken Actos instead, Graham said.

“The evidence is overwhelming,” he said. “There is not a single study where those two drugs are compared where Avandia doesn’t look worse than Actos. How many studies do you have to do before you come to your senses?”

The study was observational, with the researchers examining data on patients whose doctors had prescribed Avandia or Actos. That’s less rigorous than studies that randomly assign patients to take different drugs, and therefore cannot prove that the drug is riskier.

But Dr. Alvin Powers, a diabetes specialist at Vanderbilt University, called it “important information that’s consistent with prior studies,” even if it is not definitive. He said he doesn’t prescribe Avandia because of uncertainty over its safety.

Another AMA journal, Archives of Internal Medicine, on Monday released online an expanded analysis by the same authors who did the original one in 2007; both suggest higher heart risks for Avandia.

At its hearing next month, the FDA plans to examine the latest safety data and air internal disagreement among its scientists over what should be done.

At the FDA’s request, Glaxo began a big study last year comparing heart and stroke risks in patients on Avandia or Actos, made by Japan’s Takeda Pharmaceuticals. It aims to enroll thousands of patients, but an editorial in JAMA about the Medicare study says it would be unethical to let the study continue.

The editorial, by Dr. David Juurlink of the University of Toronto, says it is hard to understand why patients and doctors would choose Avandia when a safer alternative exists. He led a previous study of elderly diabetics in Ontario that also found higher risks with Avandia versus Actos.

Technorati Tags: Actos, Actos side effects, Avandia, Avandia side effects, diabetes drugs

Substituting brown rice or another whole grain for white rice can help reduce the risk of type 2 diabetes, new research suggests.

Five or more servings of white rice a week increased the risk of type 2 diabetes by 17 percent, according to the study, which is published in the June 14 issue of the Archives of Internal Medicine. But replacing white rice with brown rice could reduce the risk of developing type 2 diabetes by 16 percent, the study found.

“This is an important message for public health. White rice is potentially harmful for the risk of type 2 diabetes,” said the study’s lead author, Dr. Qi Sun, an instructor of medicine at Harvard Medical School and a researcher at Brigham and Women’s Hospital in Boston.

“Over the last decade, rice consumption in the U.S. has really increased a lot, but more than 70 percent of the rice consumed is white rice,” said Sun, who added, “People should replace white rice with brown rice or whole grains.”

The reason that brown rice may offer some protection, according to Sun, is that it still contains many of the nutrients and fiber that are stripped away in the production of white rice. During the refining and milling process necessary to make white rice, the rice loses a significant amount of its fiber and most of the vitamins and minerals, according to the study.

“When you have just the white rice, it’s mostly protein and starch, and you’re making freer carbohydrates that are easy to digest,” said Dr. Jacob Warman, chief of endocrinology at the Brooklyn Hospital Center in New York City.

“With white rice, the digestive enzymes can more easily penetrate the rice grains and release the starch for digestion. After ingesting white rice, blood sugar increases more rapidly,” Sun said.

To analyze how those differences affect the body over the long term, Sun and his colleagues culled data from three different studies involving nearly 200,000 participants. The studies (Health Professionals Follow-up Study and the Nurses’ Health Study I and II) included 39,765 men and 157,463 women, and contained detailed data on dietary intake that was updated every four years over a 14- to 22-year follow-up.

After adjusting the data to control for many other factors that could contribute to type 2 diabetes — such as body mass index, family history, age and other dietary habits — the researchers found that the consumption of white rice was associated with an increased risk of developing type 2 diabetes, while regular consumption of brown rice was linked to a reduced risk.

People who ate at least five servings of white rice a week had a 17 percent increased risk of type 2 diabetes, while those who ate at least two servings of brown rice a week reduced their risk of type 2 diabetes by 11 percent.

The researchers estimate that if people replaced white rice with brown rice, the risk of type 2 diabetes would go down by 16 percent.

One problem Sun and his colleagues discovered while doing the study was that brown rice consumption was relatively low during the study period. It’s only in recent years that brown rice is becoming more popular. So, the researchers also evaluated the effect that replacing white rice with whole grains would have and found that the risk of diabetes would be 36 percent lower.

“There was a very strong association between whole grains and a decreased risk of type 2 diabetes. We recommend replacing white rice with brown rice or other whole grains,” said Sun.

“In general, bulking up on grains is a good idea, and this — switching to brown rice from white — is such an easy substitution to make,” said Warman.

Technorati Tags: brown rice, Diabetes Prevention, type 2 diabetes

Danish pharmaceutical group Novo Nordisk said Saturday it was pulling 17 types of medication for treating diabetes from the Greek market following a government decree to lower prices of drugs.

“The products that are pulled from the market are the latest generation of insulin products in the pen system,” Mike Rulis, Novo Nordisk’s head of corporate communications, told AFP.

The company, the world’s largest producer of insulin to treat diabetes, said it will not stop selling the 17 products but insists on keeping their prices at the level before the Greek decree took effect on May 3, forcing it to lower prices by about 25 percent.

“That means wholesellers will no longer order these products, because they can only sell them to the pharmacies at a loss, because they will only be reimbursed at the minus 25 percent level,” Rulis said.

Novo Nordisk has however agreed to the price cut on its standard human insulin products, which diabetes patients take out of vials and inject with a syringe.

It will also make another product for diabetes sufferers, glucagon, available for free.

Rulis said about 50,000 people in Greece use the new generation products that the company will pull from the market, while another 40,000 use standard human insulin.

If Novo Nordisk complied with the 25 percent price cut on all products, its operations in Greece would become loss-making, Rulis said.

“The financial consequences for the company would be very significant,” he said, adding “a price lowering of this magnitude in Greece would automatically trigger price reductions in other countries.”

Technorati Tags: diabetes drugs, glucagon, lower prices of drugs, Novo Nordisk, treating diabetes

People who are at high risk of developing diabetes and high blood pressure but don’t have symptoms yet may still be at higher risk for heart disease, a new study reports.

“Diabetes and hypertension have reached epidemic status, not only in the U.S., but across the globe,” Dr. Henry R. Black, president of the American Society of Hypertension, said in a society news release. “We are encouraged by research that sheds light on early indicators of cardiovascular disease, which may lead to better methods of predicting, and ultimately preventing, these devastating illnesses.”

In one study, researchers analyzed data on disease-free people who were examined between 1999 and 2006, and were found to be either prehypertensive — at high risk of developing high blood pressure — or prediabetic.

One in three seemingly healthy adults were deemed to be prehypertensive and one in four were deemed to be prediabetic. One in 10 fit in both categories; they tended to be overweight and were thought to be at especially high risk of heart disease or stroke, the study authors noted.

“We would like to propose that prehypertension (blood pressure above 120/80 mm Hg) and prediabetes (blood sugar of more than 100 mg/dL) occurring together should be a red flag for urgent further evaluation,” said study lead author Dr. Alok K. Gupta, assistant professor with the Louisiana State University System in Baton Rouge, in the news release.

The study findings are scheduled to be presented Monday at the American Society of Hypertension’s Annual Scientific Meeting and Exposition, held in New York City.

Technorati Tags: Diabetes, high blood pressure, Hypertension, Pre-Diabetics

The first human trials of the latest design of an artificial pancreas for people with type 1 diabetes found the device worked without causing low blood sugar (hypoglycemia).

Ideally, this type of automated device would finally free people with type 1 diabetes from the insulin injections that many require each day, while relieving them of the constant need to check blood sugar levels and monitor the food they eat accordingly.

The device, produced through a collaboration of experts from Boston University, Massachusetts General Hospital and Harvard Medical School, delivers two hormones that are deficient in type 1 diabetes — insulin, which keeps blood sugar levels from going too high after a meal, and glucagon, a naturally occurring hormone that prevents blood sugar levels from dropping too low.

Because the device doesn’t rely on human input, it’s called a “closed-loop” system.

“A bi-hormonal closed-loop system is feasible and it can give you good average blood sugar readings,” explained one of the device’s designers, Edward Damiano, an associate professor of biomedical engineering at Boston University, and the father of a son with type 1 diabetes.

“What we’ve developed is automated decision-making software that uses a mathematical formulation to infuse varying amounts of insulin and glucagon when needed,” he explained.

Type 1 diabetes is a disease in which the body’s immune system — which normally protects you from infections and other diseases — turns against healthy cells. In type 1 diabetes, the immune system attacks beta cells in the pancreas, effectively destroying the body’s ability to produce insulin and control blood sugar levels.

What many people don’t realize, however is that beta cells aren’t the only ones damaged by the autoimmune attack. Alpha cells, which produce the hormone glucagon, are also damaged. Damiano’s colleague, Dr. Steven Russell from Harvard, said, “There is a functional deficiency in alpha cells in type 1 diabetes and they don’t work properly. They don’t secrete glucagon as they should, so an extra level of security is lost and you can wind up with hypoglycemia that can be scary and even life-threatening.”

That’s why they decided to add glucagon to their artificial pancreas to give it an added level of protection, said Russell.

In the current version of the device, the researchers tracked blood glucose via a special sensor placed into a vein. Future versions of the device will use currently available continuous blood glucose monitors (CGMs), but for this trial the researchers wanted an extremely accurate way to measure blood sugar levels so that the only variable was the mathematical formulation used to program the delivery of insulin and glucagon.

Eleven people with type 1 diabetes were included in the initial tests, and were studied in 27-hour experiments. During that time, they were hooked up to the artificial pancreas and given carbohydrate-rich meals (carbohydrates are transformed into glucose in the body).

The device responded to the rise in blood sugar levels by administering insulin. In six people, the device achieved an average blood glucose level of 140 milligrams per deciliter (mg/dl), which is well within the American Diabetes Association guidelines for care. However, five people absorbed the insulin much slower than expected, and ended up with low blood sugar levels serious enough to require intervention with additional food.

The researchers were surprised by the significant difference in blood sugar absorption rates, but went back and adjusted the mathematical formulation, and retested the device in a second experiment. This time, they achieved an average blood glucose level of 164 mg/dl, which is slightly higher than the ADA’s goal. However, there were no instances of hypoglycemia that needed intervention.

The researchers said that people using the pump would rid themselves of the need for daily injections. Instead, they might just need to change the pump site every three days, and the glucose-monitoring site once per week. No one-site integration of hormone delivery and glucose monitoring has been developed yet, although that’s the ultimate goal.

In the next trial, the researchers hope to deliver at least some of the insulin prior to a meal, which is the standard treatment. Damiano said this may be accomplished with a pre-meal button, and the user could just choose whether they were having a small-, medium- or large-carbohydrate meal.

The next set of trials will also test a device that includes insulin only, because it would likely be available faster. The reason is that glucagon is currently only FDA-approved in a freeze-dried form as an injectable rescue medication. It’s not FDA-approved yet for delivering through an insulin pump in tiny doses, as it would be in an artificial pancreas. Both Damiano and Russell think it could be possible to have an insulin-only closed-loop system available for use by patients within five years or so.

“The goal of an artificial pancreas is to try to restore normal physiology as closely as possible, and this study demonstrates that this technology is real, and it’s good in real people,” said Aaron Kowalski, assistant vice president for glucose control research and research director of the Artificial Pancreas Project for the Juvenile Diabetes Research Foundation (JDRF). “We’ve talked for many years about the theoretical potential of a closed-loop system, and now we see the real potential. These technologies are going to be built into real systems and will have the potential to transform the management of diabetes.”

Results of the study were published in the April 14 issue of Science Translational Medicine.

Technorati Tags: Artificial Pancreas, blood sugar levels, insulin injections, Type 1 Diabetes

Type 2 diabetics newly diagnosed with cancer have an increased risk of dying in the month following their cancer surgery, compared to people who are battling cancer alone.

This was particularly true for diabetics with colorectal or esophageal cancers, Johns Hopkins researchers found.

“Diabetes care should be part of cancer care,” said Hsin-Chieh “Jessica” Yeh, co-author of a study appearing in the April issue of Diabetes Care. “All the attention was on the cancer treatment and cancer care, and sometimes we overlook or forget about diabetes. This study suggests that diabetes is important for mortality, so it should be taken care of on top of the cancer care.”

But Dr. Martin S. Karpeh Jr., chairman of surgery at Beth Israel Medical Center and director of surgical oncology at Continuum Cancer Centers of New York, both in New York City, pointed out that elevated blood sugar levels — the prime characteristic of diabetes — is dangerous for people undergoing any type of surgery.

“The findings are completely consistent with other postoperative studies that have been published in recent years. We’ve known that an elevated blood sugar and diabetes increase the risk of mortality and complications from surgery,” he said. “They focused their analysis on cancer, but the same was found in non-cancer so I think the link is more with diabetes and surgery, regardless of what the reason for the surgery is.”

The bottom line for people with type 2 diabetes?

“Maintaining good health going into surgery is extremely important,” Karpeh said. “We need to emphasize the importance of good overall health. If you are a diabetic, maintaining a good blood sugar will help lower your risks of a bad outcome following any major surgery.”

People with diabetes have a higher risk of several other health conditions, including cancer, particularly of the breast, colorectal, endometrium, liver and pancreas.

Meanwhile, certain lifestyle factors, such as being overweight and sedentary, are risk factors for both type 2 diabetes and cancer.

These authors did a meta-analysis of 15 previous trials that had looked at cancer in diabetic patients.

Individuals who had been diagnosed with diabetes before their cancer surgery had a 50 percent higher chance of dying in the month after their operation compared with non-diabetic patients. This was after accounting for other factors.

There were no studies in the mix that looked at breast or endometrial cancer, so it could not be determined if there might be a link between these two as well.

It was unclear why this might be the case, but the authors had some hypotheses.

“Diabetes increases the risk of infection from surgery. High blood sugar and diabetes [increase] infections, period, with or without cancer,” said Yeh, who is an assistant professor of general internal medicine and epidemiology at Johns Hopkins University School of Medicine in Baltimore.

Also, she said, diabetes is a risk factor for cardiovascular disease and surgery increases the risk of blood clots, making diabetics doubly at risk for heart problems during surgery.

“What we would like to do now is set up research to test if better diabetes management can reduce the risk of mortality in cancer patients undergoing surgery,” said Yeh.

Technorati Tags: cancer care, Diabetes Care, Type 2 diabetics

Scientists have found evidence that older men with higher levels of selenium are less likely to suffer from dysglycemia, or improper blood-sugar metabolism.

Tasnime Akbaraly, from the University of Montpellier in France, and colleagues studied 1,162 French adults for nine years, checking their levels of selenium and monitoring whether they developed blood-sugar problems.

According to their report, published online in the journal Nutrition & Metabolism, elderly men whose selenium concentrations were in the top one-third had a significantly lower risk.

“The reason we observed a protective effect of selenium in men but not in women is not completely clear, but might be attributed to women being healthier at baseline, having better antioxidant status in general and possible differences in how men and women process selenium,” Akbaraly said in a news release from the journal’s publisher.

Technorati Tags: blood-sugar, Diabetes, selenium

New research suggests that young children and teenagers with type 1 diabetes could benefit by using an artificial pancreas device to lower the risk of dangerously low blood sugar levels during sleep and help them control their disease.

The findings, which appear in the Feb. 5 issue of The Lancet, examined use of an artificial pancreas by people aged 5 to 18 in a hospital setting.

The device, which combines blood sugar sensors and insulin pumps, give doses of insulin as needed to patients as they sleep.

Controlling blood sugar at night is a challenge for people with type 1 diabetes. If blood sugar levels drop to dangerously low levels, diabetics can suffer from seizures, coma and even death.

The researchers found that the study participants spent twice as much time during the night at targeted glucose levels when they used the artificial pancreas system compared to when they tried a “manual” approach.

“These studies show that automated systems not only can help people manage diabetes by maintaining good control, they will also improve quality of life for the people with type 1 diabetes and their families by lowering the risk for hypoglycemia,” principal investigator Roman Hovorka, of the Institute of Metabolic Science at the University of Cambridge in England, said in a news release from the journal. “These results suggest that closed-loop devices may be able to significantly lower the patient’s risk of developing complications later in life by reducing or even overcoming the burden of hypoglycemia.”

Technorati Tags: Artificial Pancreas, hypoglycemia, manage diabetes, Type 1 Diabetics