Published online before print November 10, 2005, doi: 10.1161/01.ATV.0000195790.24531.4f
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© 2006 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Effects of Pioglitazone on Lipoproteins, Inflammatory Markers, and Adipokines in Nondiabetic Patients with Metabolic Syndrome
From the Division of General Internal Medicine (P.O.S., L.T.B.), Institute for Translational Medicine and Therapeutics (P.O.S., L.T.B., M.L.W., D.J.R.), Division of Cardiovascular Medicine (F.S., M.P.R.), and Center for Clinical Epidemiology and Biostatistics (P.O.S., J.C., M.P.R.), University of Pennsylvania School of Medicine, Philadelphia, Pa. Current affiliation for P.O.S. is Wyeth Research, Collegeville, Pa.
Correspondence to Daniel J. Rader, Institute for Translational Medicine and Therapeutics, University of Pennsylvania Medical Center, 654 BRBII/III Labs, 421 Curie Blvd, Philadelphia, PA 19104-6160. E-mail rader{at}mail.med.upenn.edu
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.
We performed a detailed evaluation of the lipid effects of pioglitazone (PIO) in nondiabetic patients with metabolic syndrome. The primary finding was that PIO raised high-density lipoprotein cholesterol by 14% compared with placebo, without significant changes triglycerides or low-density lipoprotein cholesterol. Our results suggest that PIO may be useful as an antiatherosclerotic strategy in this nondiabetic population.
Key Words: atherosclerosis • lipids • lipoproteins • inflammation • metabolic syndrome
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