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Avandia (Rosiglitazone) Lowers Markers for Cardiovascular Inflammation in Diabetic Patients: Presented at ADA

By Bruce Sylvester
Special to DG News

SAN FRANCISCO, CA -- June 17, 2002 -- Avandia® (rosiglitazone) appears to lower markers of cardiovascular inflammation -- a precursor of atherosclerosis and heart disease -- in diabetic patients.

Blood-borne oxygen free radicals can injure vessel linings, initiating vascular inflammation that induces atherosclerosis and heart disease. The investigators found that rosiglitazone, a widely used insulin sensitizer, has a profound inhibitory effect on oxygen free radicals. They reported their findings here Saturday at the annual meeting of the American Diabetes Association (ADA).

Atherosclerosis is a leading cause of heart disease, which diabetics suffer at twice the rate of non-diabetics.

"Lowering inflammation is fundamental in the prevention of atherosclerosis and cardiovascular disease," said Paresh Dandona, MD, professor of endocrinology at the University of Buffalo School of Medicine and Biomedical Sciences, in Buffalo, New York, United States. "Other research indicates that rosiglitazone lowers markers of cardiovascular disease in patients at risk for diabetes. We took the research one step further, studying diabetics. We found a significant anti-inflammatory effect emerging from blood data acquired from our diabetic subjects."

The researchers enrolled 11 obese patients with Type 2 diabetes and initiated a six-week daily dosing regimen of rosiglitazone 4 mg/day. They took fasting blood samples at 0, 1, 2, 4, 6 and 12 weeks and analyzed the blood for concentrations of three inflammatory markers and oxygen free radicals.

The investigators measured nuclear factor k (NF-kB) binding activity in mononuclear cells (MNC), reactive oxygen species (ROS) generation by MNC, plasma monocyte chemoattractant protein-1 (MCP-1) and C-reactive protein (CRP), as well as brachial artery reactivity using post-ischemic flow mediated dilation (FMD).

At week 6, blood glucose concentration decreased from 157±16 to 127±9 mg/dL and insulin concentration fell from 32.6±4.6 to 16.1±2.2 mU/mL (p<0.05). NF-kB binding activity in MNC nuclear extract also declined significantly (p<0.02); inhibition was significant by week 1 (77±13 percent of the basal level) and continued up to week 6 (66±10.6 percent of basal).

ROS generation by MNC fell significantly to 94±6 percent by week 1 and 66±10 percent at week 6 (p<0.05). Rosiglitazone treatment also reduced plasma MCP-1 (75 percent of the basal level; p<0.05) and CRP (70 percent of basal; p<0.05).

FMD at baseline was 3.4±1.2 percent, which increased to 8.6±1.9 percent (p<0.05) at week 6. Nitroglycerin-induced endothelium independent vasodilatation increased from 11.8±1.4 percent at baseline to 16.7±2.3 percent at week 6 (p<0.05).

"Rosiglitazone exerts a profound ROS suppressive and anti-inflammatory effect as reflected at the cellular and molecular level, and in plasma. Rosiglitazone also improves vascular reactivity," the authors concluded. "These observations may have implications for atherogenesis in the long-term in patients treated with rosiglitazone. At 12 weeks, after the subjects had been off treatment for six weeks, inflammatory markers had returned to pre-trial levels."

Rosiglitazone sensitizes cells to insulin, causing them to absorb more of the reduced amount of bodily insulin that diabetics produce.

The study was supported by GlaxoSmithKline, the manufacturer of Avandia.

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