A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism

Study Objectives I. Primary Objective: * To determine the effects of LY518674 on the Apo A-I production rate (calculated from the fractional synthetic rate and the fractional catabolic rate) in subjects with the metabolic syndrome and low HDL-C. II. Secondary Objectives: * To determine the effects of LY518674 on markers of reverse cholesterol transport by analyzing changes in serum cholesterol efflux capacity (an in vitro cell-based assay). * To determine the effects of LY518674 on the activity of lecithin cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), lipoprotein lipase, hepatic lipase, and endothelial lipase. * To determine the effects of LY518674 on plasma lipids, lipid subfractions, free fatty acids, and the free fatty acid metabolite, beta-OH butyrate. * To determine the effects of LY518674 on high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particle size using nuclear magnetic resonance (NMR). * To determine the effects of LY518674 on Apo A-II and Apo B-100 kinetics. * To determine the effects of LY518674 on hsCRP. * To determine the safety and tolerability of LY518674 Study Design: Study H8D-MC-EMBG is a single site, randomized, placebo-controlled, double-blind, parallel study. A minimum of 40 subjects with low HDL cholesterol and metabolic syndrome will be randomized to receive double-blind administration of LY518674 100 mcg/day or placebo for 8 weeks. There is a safety visit every 2 weeks after treatment has been initiated, resulting in 7 visits over 10 weeks. There are 2 inpatient visits at zero and eight weeks.