Abstract 17927: Acipimox Does Not Improve Endothelial Function and Insulin-Stimulated Vasodilation in Patients With Metabolic Syndrome

Abstract

Introduction: Insulin resistance increases circulating free fatty acid (FFA) concentrations, which causes the release of inflammatory cytokines and induces endothelial dysfunction. Acipimox reduces FFA efflux and may improve insulin sensitivity and endothelium-dependent microvascular vasodilation. Hypothesis: We hypothesize that acipimox treatment will improve insulin-stimulated forearm blood flow (FBF) compared to placebo in volunteers with metabolic syndrome. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial (NCT00759291) evaluating 1-week of acipimox 250 mg QID on insulin-stimulated FBF in patients with and without metabolic syndrome. Results: Sixteen patients received acipimox (6 metabolic syndrome and 10 healthy controls). Patients with metabolic syndrome were older (63.8 vs 49.9 years old, p<0.001) with higher baseline insulin levels (15.9 vs 3.5 μU/mL, p=0.002), and trended towards higher BMIs (30.9 vs 24.6 kg/m 2 , p=0.083). Baseline insulin sensitivity by Homeostatic Model Assessment for Insulin Resistance (HOMA IR) differed between controls and those with metabolic syndrome (0.68 vs 3.28, p=0.001) but did not change with acipimox (p=0.540, Panel A). Insulin stimulation increased FBF in patients treated with placebo (p=0.01, Panel B) and acipimox (p=0.03, Panel C) but was not augmented by acipimox in participants with metabolic syndrome or healthy controls (Panel D and E). In multivariable-adjusted regression analysis, acipimox did not increase FBF, even after adjusting for baseline FBF and key baseline differences, including metabolic syndrome. Conclusion: Acipimox did not improve insulin sensitivity and had no effect on microvascular endothelial dysfunction assessed by insulin-stimulated FBF. This suggests that FFA modulation does not reverse microvascular dysfunction in patients with metabolic syndrome.