July 20, 2007

Team studying drug to delay diabetes onset

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Stephen Davis, Ph.D., and teammates, from left, Hannah Blair, Donna Tate and Jennifer Perkins, M.D., are studying a drug that may help delay the onset of diabetes. (photo by Susan Urmy)

Team studying drug to delay diabetes onset

Vanderbilt University Medical Center diabetes researchers are launching a study to examine how Ramipril, a commonly prescribed medication for treating high blood pressure, could be a significant tool for preventing or delaying the onset of type 2 diabetes.

“We have already found that it can return someone with pre-diabetes back to a normal blood glucose level, so the big question is how does this work?” said Stephen Davis, Ph.D., director of VUMC's Division of Diabetes, Endocrinology & Metabolism.

“The mechanisms of how Ramipril affects blood glucose are not known. I think this is going to be the first study, and we hope a breakthrough study, that can provide this important information.”

Ramipril belongs to a class of drugs known as angiotensin converting enzyme (ACE) inhibitors, which are used for treating high blood pressure, heart failure and kidney failure associated with high blood pressure.

ACE inhibitors such as Ramipril work by reducing the body's production of angiotensin II, which in turn relaxes arterial muscles and allows arteries to enlarge to help lower blood pressure.

“The question we are seeking to answer is how does a blood pressure pill work similarly to medications that we use for lowering blood glucose?

“What my laboratory is undertaking is to find the reasons behind how this medication can delay the onset of diabetes,” Davis said.

Davis said the idea to use ACE inhibitors such as Ramipril to treat diabetes came from previous studies where the goal was aggressive management of high blood pressure in people with diabetes and pre-diabetes, those on the brink of developing diabetes.

“They found that by taking Ramipril, the progression from pre-diabetes to diabetes was reduced,” Davis said. “In a significant number of these people, not only did they not develop diabetes, their blood glucose returned to normal. This is a very exciting finding.”

The explosion in the number of people with diabetes is one of the primary public health problems facing the nation.

According to the Centers for Disease Control and Prevention (CDC):

• The number of people with diabetes in the United States soared from 5.6 million in 1980 to more than 21 million in 2006, an increase of nearly 400 percent;

• People age 65 and older account for approximately 38 percent of that total, which is growing by 15 percent each year;

• Nearly 11 percent of all Tennesseans have diabetes;

• Presently, as many as 64 million Americans already have metabolic syndrome, a cluster of health complications that are precursors to developing type 2 diabetes. They include high blood pressure, high cholesterol, too much abdominal fat and elevated blood glucose.

“Two out of every three Americans are overweight. When you become overweight the body's insulin may not work correctly to control glucose, because it can no longer unlock cells to make them use glucose to lower blood pressure,” Davis said.

“When you are insulin-resistant the insulin key doesn't work. This is one of the reasons why we are seeing so much more diabetes.”

For this study, Davis and his team are seeking subjects age 18-65 with pre-diabetes to study over a six-month period.

“We are looking for individuals with elevated blood glucose, but not to the point of having diabetes, and who also have elevated blood pressure. These are the folks who are headed toward diabetes but they don't have it yet,” he said.

Appropriate study candidates are age 18 to 65, are overweight and may have a family history of diabetes. They may also have been told previously their blood glucose was elevated, but not quite enough for diabetes, and they will also have elevated blood pressure.

“After six months we will be looking to see if Ramipril has increased the amount of insulin produced by the body, or if it has allowed better use of the insulin made by the body,” he said.

“We will also look for signs of inflammation within blood vessels and whether that has been reduced. We'll also be looking at cholesterol (triglycerides) to see if those have improved.”

“We really have to put the brakes on the diabetes epidemic, and I think this study is a possible step toward that goal,” he said.

For more information on the study, call 936-1824.