Effects of pioglitazone on lipoproteins, inflammatory markers, and adipokines in nondiabetic patients with metabolic syndrome

Objective: The purpose of this research was to evaluate the short-term effects of pioglitazone (PIO) on high-density lipoprotein cholesterol (HDL-C) and other metabolic parameters in nondiabetic patients with metabolic syndrome (MetSyn). Methods and Results: Sixty nondiabetic adults with low HDL-C and MetSyn were randomized to PIO or matching placebo for 12 weeks. PIO increased HDL-C by 15% and 14% at 6 and 12 weeks, respectively, compared with placebo (P < 0.001). Changes in HDL-C were correlated to changes in adiponectin (r = 0.34; P = 0.01) but not to changes in insulin resistance. PIO did not affect serum triglycerides or low-density lipoprotein (LDL) cholesterol concentrations but reduced the number of small LDL particles by 18% (P < 0.001). PIO reduced median C-reactive protein levels by 31% (P < 0.001) and mean resistin levels by 10% (P = 0.02) while increasing mean serum levels of adiponectin by 111% (P < 0.001) compared with placebo. PIO did not affect weight and modestly decreased insulin resistance. Conclusions; In nondiabetic patients with low HDL-C and MetSyn, PIO significantly raised HDL-C and favorably affected lipoprotein particle size, markers of inflammation, and adipokines without changes in triglycerides, LDL-C, or weight. These results suggest that PIO has direct effects on HDL, which may contribute to its antiatherogenic effects.