Abstract 3705: Pioglitazone Augments Niacin-Induced Increases in Adiponectin in Non-Diabetics with Metabolic Syndrome and Low HDL

Abstract

Background Niacin and pioglitazone (PIO) increase HDL by uncertain mechanisms. Both increase adiponectin, whose effects on carbohydrate and fatty acid metabolism may benefit HDL indirectly. Little is known of the combined effects of the drugs on adiponectin and other adipokines. We hypothesized that PIO would complement changes in adipokines from niacin, and in turn, augment HDL. Methods In an open-label run-in, non-diabetics with low HDL titrated from 0 to 2 g extended-release niacin over 4 weeks, and were randomized to add PIO 30 mg or placebo in a double-blind manner. After 6 weeks, PIO was increased to 45 mg for another 6 weeks. We assessed changes in fasting adiponectin, resistin, complement C3 (the serum-detectable precursor of acylation stimulating protein), free fatty acids (FFA), hydroxy-butyrate (HBA), and triglycerides (TG), and their relationship to changes in HDL. Results Of 72 completers, 34 took niacin and placebo and 38 took niacin and PIO. The table shows absolute and relative change of each analyte from baseline to 16 weeks. Relative change in adiponectin was strongly correlated with change in HDL (Spearman’s rho +0.49, p<0.0001), as was change in TG (rho −0.50, p<0.0001); the other analytes had little influence. On multivariable regression, change in HDL was predicted by change in adiponectin (p=0.0001) and TG (p<0.0001), which remained significant on adjustment for changes in glucose and insulin. Conclusion Pioglitazone augments niacin-induced changes in adiponectin and complement C3 thought to be favorable, and neutralizes niacin’s unfavorable increase in FFA. Adiponectin strongly predicted HDL after adjustment for TG. Since PIO had no independent effect on TG, we speculate that additional HDL-raising from PIO is mediated by the large increase in adiponectin. In summary, PIO enhances HDL-raising from niacin in proportion to increased adiponectin.