Soluble CD36 and Risk Markers of Insulin Resistance and Atherosclerosis Are Elevated in Polycystic Ovary Syndrome and Significantly Reduced During Pioglitazone Treatment

OBJECTIVE: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS). RESEARCH DESIGN AND METHODS: Thirty PCOS patients were randomized to 30 mg/day pioglitazone or placebo for 16 weeks. Fourteen weight-matched healthy female subjects were included as control subjects. sCD36, oxidized LDL (oxLDL), high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, euglycemic-hyperinsulinemic clamps, and whole-body dual-energy X-ray absorptiometry scans were performed. RESULTS: sCD36 (2.87 relative units [0.88-9.36] vs. 1.67 relative units [0.72-3.89]), oxLDL (44.9 units/l [26.9-75.1] vs. 36.1 units/l [23.4-55.5]), and hsCRP (0.26 mg/dl [0.03-2.41] vs. 0.12 mg/dl [0.02-0.81]) were significantly increased in PCOS patients versus control subjects (geometric mean +/- 2 SD). In PCOS, positive correlations were found between central fat mass and sCD36 (r = 0.43), hsCRP (r = 0.43), and IL-6 (r = 0.42) (all P < 0.05). After adjusting for fat mass, sCD36 and oxLDL correlated inversely with measures of insulin-stimulated glucose metabolism and positively with lipid oxidation during insulin stimulation in PCOS patients and control subjects (n = 44). sCD36 and oxLDL were significant independent predictors of glucose and lipid metabolism, whereas hsCRP and IL-6 showed no significant contribution. Following pioglitazone treatment, insulin sensitivity increased, whereas sCD36 (3.21 relative units [0.76-13.6] vs. 2.33 relative units [0.84-6.46]) and hsCRP decreased (P < 0.05). No significant changes were measured in body composition. CONCLUSIONS: sCD36 and oxLDL correlated with measures of insulin sensitivity independent of central fat mass. Pioglitazone treatment reduced sCD36 while improving insulin-stimulated glucose metabolism, further supporting the association between sCD36 and insulin resistance in PCOS.