Inhibition of lipolysis improves insulin sensitivity in protease inhibitor-treated HIV-infected men with fat redistribution

Abstract

Background: Fatty acid concentrations are increased in patients with HIV and fat redistribution and may contribute to insulin resistance in this population. Objective: We determined the effects of acute inhibition of lipolysis on insulin sensitivity in HIV-infected patients with fat redistribution who were receiving a protease inhibitor. Design: Seven HIV-infected men [age: 45 ± 2 y; body mass index (in kg/m2): 28.8 ± 1.9] with a fasting insulin concentration ≥ 104 pmol/L (15 μIU/mL), combined visceral adiposity and peripheral lipoatrophy, and receiving a protease inhibitor were studied. Tolbutamide-modified frequently sampled intravenous-glucose-tolerance tests (FSIGTTs) were performed after randomized double-blind administration of acipimox (500 mg at -90 and 0 min), a potent inhibitor of lipolysis, and placebo. The subjects completed 2 FSIGTTs separated by 3-7 d. Results: At baseline, fasting insulin and fatty acid concentrations were 27.6 ± 5.0 μIU/mL and 0.83 ± 0.08 mmol/L (normal range: 0.1-0.6 mmol/L), respectively. Fatty acid concentrations were significantly reduced after acipimox compared with placebo (fatty acid area under the curve: acipimox = 73 ± 8 compared with placebo = 122 ± 12 mmol · 270 min/L, P = 0.002). Acipimox treatment resulted in a significant increase in the insulin sensitivity index (acipimox = 1.63 ± 0.5 compared with placebo = 0.88 ± 0.3 x 10-4 · min-1 · μIU/mL, P = 0.015). Conclusions: Acute inhibition of lipolysis and reduction in fatty acid concentrations are associated with improved insulin sensitivity in patients with HIV lipodystrophy and hyperinsulinemia. Further studies are needed to determine whether long-term antilipolytic strategies to reduce fatty acid concentrations may be useful in treating the metabolic disturbances associated with HIV lipodystrophy.