Abstract 19564: Role of Insulin Resistance and Excess Free Fatty Acids in Determining Endothelial Function in the Metabolic Syndrome
Introduction: It is hypothesized that insulin resistance and endothelial dysfunction are reciprocally linked, though clinical data are limited. In particular, impaired endothelial insulin signaling is thought to result in endothelial dysfunction. Excess circulating free fatty acids (FFAs) are hypothesized to impair insulin signaling and result in both insulin resistance and the associated endothelial dysfunction.
Aims: We examined the relationship between insulin resistance and endothelial function in the metabolic syndrome, a clinical state of insulin resistance. We also tested whether lowering of FFAs would improve endothelial function in persons with the metabolic syndrome.
Methods: A total of 70 adults, 39 with the metabolic syndrome and 31 healthy controls, were studied. Subjects underwent euglycemic hyperinsulinemic clamp to measure insulin resistance (‘M’, mg/kg/min) and insulin-stimulated, endothelium-dependent vasodilation (%), as well as ultrasound-measured brachial artery flow-mediated dilation (FMD, %) to measure endothelial function. Thirty-five subjects, 18 with the metabolic syndrome and 17 controls, completed a double-blinded, placebo controlled crossover trial to examine the effects of 7 days of FFA lowering with acipimox on endothelial function and insulin resistance.
Results: FFA levels were higher in the metabolic syndrome (p < 0.01). Persons with the metabolic syndrome were insulin resistant compared with control subjects (M 5.1 (1.4) mg/kg/min vs. 9.7 (3.9) mg/kg/min, p < 0.001), but FMD (10.9 (6.4) % vs. 10.7 (5.0)%, p = 0.92) and insulin stimulated vasodilation (36.9 (32.4) % vs. 86.6 (140) %, p = 0.31) were not different between groups. Acipimox therapy improved insulin resistance approximately 20% (p < 0.05) but did not alter FMD (p = 0.67) or insulin-stimulated dilation (p = 0.26).
Interpretation: These data demonstrate preserved endothelial function in persons with the metabolic syndrome despite severe systemic insulin resistance, and no effect of FFA lowering therapy on endothelial function despite improvement insulin sensitivity. Insulin resistance and elevated FFA levels may not be sufficient to cause endothelial dysfunction in humans.
- © 2012 by American Heart Association, Inc.