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 pioglitazone, 30 mg/day or placebo for 16 weeks. Fourteen weight-matched healthy females were included as controls. sCD36, oxidized LDL (oxLDL), high sensitive CRP (hsCRP), interleukin 6 (IL-6), euglycemic-hyperinsulinemic clamps, and whole body DXA-scans were performed. Results: sCD36 (2.87 (0.88 - 9.36) vs. 1.67 (0.72 - 3.89) relative units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). 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 controls (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(0.76 - 13.6) vs. 2.33 (0.84 - 6.46) relative units) 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