Effect of Rosiglitazone on Endothelial Function and Inflammatory Markers in Patients With the Metabolic Syndrome

OBJECTIVE:--The aim of this study was to assess the effect of rosiglitazone on endothelial function and inflammatory markers in patients with the metabolic syndrome. RESEARCH DESIGN AND METHODS--This was a randomized, double-blind, controlled clinical trial. One hundred subjects (54 men and 46 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III, were followed for 12 months after random assignment to rosiglitazone (4 mg/day) or placebo. Primary end points were flow-mediated dilation and high-sensitivity C-reactive protein (hs-CRP) levels; secondary end points were lipid and glucose parameters, homeostasis model assessment (HOMA) of insulin sensitivity, endothelial function score, and circulating levels of interleukin (IL)-6, IL-18, and adiponectin. RESULTS:--Compared with 60 control subjects matched for age and sex, patients with the metabolic syndrome had decreased endothelial function, raised concentrations of inflammatory markers, and reduced insulin sensitivity. After 12 months, subjects with the metabolic syndrome receiving rosiglitazone showed improved flow-mediated vasodilation (4.2%, P < 0.001) and reduced hs-CRP levels (-0.7 mg/dl, P = 0.04), compared with the placebo group. Moreover, HOMA (-0.8, P = 0.01) and serum concentrations of IL-6 (-0.5 pg/ml, P = 0.045) and IL-18 (-31 pg/ml, P = 0.036) were significantly reduced in subjects receiving rosiglitazone, whereas adiponectin levels showed a significant increment (2.3 [micro]g/ml, P = 0.02). High-density lipoprotein-cholesterol levels increased more and triglyceride levels decreased more in the rosiglitazone group compared with the placebo group. At 1 year of follow-up, 30 subjects receiving rosiglitazone still had features of the metabolic syndrome, compared with 45 subjects receiving placebo (P < 0.001). CONCLUSIONS:--Rosiglitazone might be effective in reducing the prevalence of the metabolic syndrome.