Diabetes Forecast

The Heart of the Matter

Preventing atherosclerosis in people with type 2 diabetes

Researcher: Peter D. Reaven, MD
Occupation: Endocrinologist, Carl T. Hayden VA Medical Center Phoenix
Focus: Cardiovascular Disease and Diabetes Research
Funding: ADA Clinical Research Grant

The name itself is vividly descriptive, if you happen to know ancient Greek: athero, for "gruel" or "paste," and sclerosis, for "hard." When it's taking place deep inside the body's most important blood vessels, atherosclerosis is a serious problem. Over time, a sludge of fats, calcium, and cholesterol accumulates on the inside of major blood vessels, forming a crusty buildup called a plaque.

"In a healthy young person, there's very little accumulation," says endocrinologist Peter D. Reaven, MD, of the Carl T. Hayden VA Medical Center in Phoenix. "Eventually, if the blockage gets sufficiently large, it can lead to reduced blood flow to the heart or other organs." At worst, bits of the plaque break away from the walls of the artery and block the blood vessel entirely. The result is a blood clot that can cause a heart attack or stroke.

The top risk factors for atherosclerosis are smoking, high blood pressure, high cholesterol, and diabetes. For reasons doctors aren't sure of, diabetes weakens the ability of the circulatory system to flush out contaminants that build up into plaque. The result is a powerful correlation among diabetes, cardiovascular disease, and death. "For people with diabetes, there's a two- or three-fold increase in terms of cardiac risk," says Reaven. And the number one cause of death for people with diabetes is heart disease.

But is there anything people with type 2 diabetes and atherosclerosis can do to reverse the buildup of this deadly "hard paste"? Reaven recently began research to find out, with the help of a grant from the American Diabetes Association.

Reaven was part of a nationwide team of doctors from the Department of Veterans Affairs who looked at the interaction between diabetes and atherosclerosis. Beginning in 2001, they studied more than 300 men with type 2 diabetes to see if tight control over blood glucose levels could help slow the progression of atherosclero

sis. In the process, they looked hard at the roots of heart disease and the role of diabetes. "We wanted to know why person A develops atherosclerosis, but not person B," Reaven says. "Does tight glycemic control reduce the likelihood of a cardiac event?"

To find out, Reaven and his colleagues had to take a look at the buildup inside patients' arteries. They turned to computer-aided tomography, or CAT, scans, to create detailed cross sections of patients' bodies. The doctors were looking for a key component of the plaque that clogs arteries: calcium. In a 2004 study published in the journal Diabetologia, Reaven found solid links between the amount of calcium in arteries and the seriousness of cardiovascular problems.

Though the everyday mineral is just one of the things that builds up inside the arteries when atherosclerosis gets going, calcium shows up a distinct white on X-rays and CAT scans, allowing Reaven to measure the extent of the blockage in arteries over time. "We measured calcium levels in coronary arteries and sections of the abdominal aorta, the idea being we'd get a more comprehensive look at atherosclerosis," Reaven says.

The hundreds of veterans who took part in the VA study—almost all of them men in their early 60s—showed mixed results. Patients who had low levels of plaque in their arteries at the beginning of the study tended to benefit from tight control over their blood sugar over time. But in people whose arteries were already clogged with plaque, "it doesn't look like glycemic control had an effect," Reaven says.

Some of the study's results were presented at the ADA's annual conference earlier this year, but Reaven is still plumbing the data, which he believes could yield more information on everything from cardiovascular disease and diabetes to retina damage. Already, the findings may prove useful in helping doctors design treatments to stave off the development of clogged, stiff arteries in people with type 2 diabetes.

As people develop it at younger and younger ages, controlling the development of atherosclerosis could become something doctors and patients need to think about from the outset.

"Our data suggest it may depend on whether you get to them early enough," Reaven says. "Early enough in the process, our data would suggest that intensive glucose lowering would be useful."

To sponsor an ADA research project at the Research Foundation's Pinnacle Society level of $50,000 or more, call Elly Brtva, MPH, managing director of Individual Giving, at (703) 253-4377, or e-mail her at ebrtva@diabetes.org.



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