Insulin Sensitizer Has Anti-Inflammatory Effect in Diabetics

SAN FRANCISCO -- A drug used widely as an insulin sensitizer appears also to have a significant anti-inflammatory effect in diabetics, a property that could make it useful in helping to prevent heart disease in these patients, a study by endocrinologists at the University at Buffalo has found.

Results of the research, involving the drug rosiglitazone, were presented here today (June 15, 2002) at the annual meeting of the American Diabetes Association. Rosiglitazone is sold under the brand name Avandia(r).

UB endocrinologists, led by Paresh Dandona, M.D., professor of medicine and head of the Division of Endocrinology in the UB School of Medicine and Biomedical Sciences, have been studying the anti-inflammatory properties of insulin and insulin sensitizers and their potential use in treatment and prevention of atherosclerosis, one of the leading causes of heart attacks.

Atherosclerosis, or hardening of the arteries, begins as an inflammation of the blood-vessel wall. Persons with diabetes are at increased risk of developing atherosclerosis and heart disease. Dandona's lab has shown in research with a small group of obese non-diabetic volunteers that rosiglitazone decreased the levels of oxygen free radicals which can begin the inflammation cascade by injuring blood-vessel linings. The drug also decreased the levels of several blood markers of inflammation.

The current study involved 11 obese patients with Type 2 diabetes. In this disease, also referred to as adult-onset diabetes, the body produces adequate amounts of insulin, but cells don't respond to its action. Rosiglitazone is prescribed to break down this resistance to insulin.

Researchers collected blood samples from the diabetic volunteers and started them on a six-week course of daily rosiglitazone. They repeated the blood sampling four times during the six weeks of treatment and again at 12 weeks, and analyzed the samples for concentration of three inflammatory markers and for the presence of oxygen free radicals.

Results showed that the drug exerted a "profound" suppressive effect on free radicals and on other mediators of inflammation in the blood.

"The ability to reduce inflammation is crucial for preventing atherosclerosis and cardiovascular disease, " said Dandona. "Previous data demonstrated rosiglitazone's effectiveness in reducing key markers of cardiovascular disease in patients at risk for diabetes. This study in people with diabetes further underscores rosiglitazone's potential to have a cardio-protective effect."

Analysis of blood samples showed that at six weeks, free radical generation had dropped about 34 percent from baseline. Concentration of the inflammatory markers plasma monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP) fell by 25 percent and 30 percent, respectively, at six weeks. At 12 weeks inflammatory markers had returned to baseline.

Rosiglitazone also improved vascular reactivity - the ability of vessels to expand and contract in response to changes in blood flow -- which is crucial for maintaining healthy blood pressure and blood flow to vital organs.

Also involved in the study, all from UB's department of Medicine, were Priya Mohanty, M.D.; Ahmad Alijada, Ph.D.; Husam Ghanim; Deborah Hofmeyer; Devjit Tripathy, M.D., and Sandeep Dhindsa, M.D.

The study was funded by GlaxoSmithKline, manufacturer of Avandia.