International Research Links Inflammation and Type 2 Diabetes; Insights Open New Pathways for Prevention and Treatment

6/17/2002

From: Diane Tuncer, 703-299-5510 Mark Overbay, 703-549-1500, ext 2290 Newsroom June 14-18: Room 220, Moscone Center, San Francisco, Calif., 415-978-3733

SAN FRANCISCO, June 17 -- A series of international research reports have now linked inflammation to type 2 diabetes, opening new pathways for prevention and treatment of the disease and its complications, according to reports here Sunday at the American Diabetes Association's 62nd Annual Scientific Sessions.

"In the past year, about six studies have shown that markers of inflammation predict development of type 2 diabetes," reported Joshua Barzilay, M.D., of the division of endocrinology at Kaiser Permanente of Georgia, who spoke at a symposium on inflammation and diabetes. "One of the purposes of this meeting is to review recent findings and suggest new areas for investigation in this brand new field, including possible ways to reduce inflammation as a means of preventing or forestalling illness."

More than 17 million Americans have diabetes, a group of serious diseases characterized by high blood sugar levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputations. It is the fifth-leading cause of death by disease in the U.S.

UNDERSTANDING INFLAMMATION

Inflammation is the way the body normally responds to injury -- sending specialized blood cells to the area to destroy and clean up damaged cells -- and can be seen on the skin, for example, as redness, swelling, and heat. But when the immune system malfunctions, such as in rheumatoid arthritis, the inflammatory process itself damages healthy tissue, such as joints.

In recent years, researchers have discerned that inflammation may play a role in diseases not previously considered inflammatory, such as coronary heart disease. As a result, doctors theorize that the anti-inflammatory effects of aspirin -- long recommended to heart patients for its anti-clotting ability -- also may be yielding benefits.

INFLAMMATION AND DIABETES

The link between heart disease and inflammation was made, in part, when doctors found higher levels of markers of inflammation in the blood of people with heart disease and then found that such markers also predicted risk for a heart attack. Higher levels of those same markers have now been found in people with diabetes and those at high risk for diabetes.

One of those markers is CRP (C-reactive protein), which appears to be elevated in the presence of heart disease, diabetes, and obesity. "It's possible that if you have excessive fat, substances secreted from fat stimulate markers of inflammation," explained Vivian Fonseca, M.D., professor of medicine at Tulane University Health Sciences Center, New Orleans, who spoke at a symposium on diabetic dyslipidemia and inflammation. "So inflammation may be the common link for developing insulin resistance, diabetes, and heart disease, making it very attractive to monitor and treat high CRP levels."

In an ancillary study of the Atherosclerosis Risk in Communities (ARIC) project, an NIH funded research effort, more than 10,000 people who did not have diabetes were followed with blood sampling for nine years. The researchers found an association between developing diabetes and a series of inflammatory markers, especially sialic acid, according to Bruce Duncan, M.D., Ph.D., associate professor in the School of Medicine of the Federal University of Rio Grande do Sul. "The quarter of the sample with the highest levels of these markers were at a 20 percent to 60 percent higher risk than the lowest quarter, clearly suggesting that something about the inflammatory response is related to diabetes."

In Kuwait, research found that "the percentage of diabetic individuals who were in the highest 20 percent of CRP values were four times more likely to be suffering from cardiovascular disease compared to those who were in the lowest 20 percent of CRP," according to Nabila Abdella, MB, CHP, FRCP, Professor of Medicine at Kuwait University. Therefore she concludes that a high CRP value is indicative of a high risk for cardiovascular disease among those with diabetes and warrants more aggressive management, including tight control of blood sugar, blood pressure, and high cholesterol, as well as daily aspirin.

In a Hong Kong study, a high CRP level was found to be an independent predictor for development of diabetic nephropathy.

STEPS TOWARD PREVENTION

Although some research is underway to explore the benefits of potent anti-inflammatory drugs, other studies have shown that several drugs already widely used by people with diabetes have anti-inflammatory benefits.

Rosiglitazone (Avandia) is one of a class of drugs (thiazolidinediones) known to lower blood sugar and is widely prescribed for type 2 diabetes. In a recent study, standard doses were given to a group of people with diabetes and blood samples were taken at baseline and at 1, 2, 4, 6, and 12 weeks. A series of markers of inflammation, including CRP and NFkappaB, were measured.

"Not only did average blood glucose levels fall from 147 to 127 as expected, but all the indicators of inflammation fell by 20 percent to 40 percent by week 6, when the drug was discontinued," reports Paresh Dandona, M.D., Ph.D., Head of the Division of Endocrinology, Diabetes, and Metabolism at the State University of New York at Buffalo. "This leads us to speculate that patients treated with rosiglitazone might not develop atherosclerosis at the high rate usually seen in diabetes." In addition, Dr. Dandona suggested that such anti-inflammatory treatment of those at risk for diabetes might help prevent the disease itself.

A class of drugs used to reduce high cholesterol levels -- the HMG-CoA reductase inhibitors, nicknamed "statins," -- are also widely used by people with diabetes and have also been found to reduce inflammation. Now, a study has been made of Saskatchewan adults who were newly started on any of the oral hypoglycemic agents used to treat type 2 between the years of 1991 and 1996. Records were kept to determine who was also given a statin, to discern whether such treatment might increase the period of time to when these patients were prescribed insulin for their diabetes, a signal of worsening control.

"We found that statin use was associated with an average 10-month delay before starting insulin treatment," reported Jeffrey A. Johnson, Ph.D., associate professor of Public Health Sciences at the University of Alberta, Canada. His group recommended that the potential of statins to delay onset of diabetes in high-risk individuals be evaluated.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.