Effects of Insulin-Like Growth Factor (IGF)-I/IGF-Binding Protein-3 Treatment on Glucose Metabolism and Fat Distribution in Human Immunodeficiency Virus-Infected Patients with Abdominal Obesity and Insulin Resistance

• Published in: The journal of clinical endocrinology and metabolism 2010-09, Vol.95 (9), p.4361-4366
• Main Authors: Rao, Madhu N., Mulligan, Kathleen, Tai, Viva, Wen, Michael J., Dyachenko, Artem, Weinberg, Melissa, Li, Xiaojuan, Lang, Thomas, Grunfeld, Carl, Schwarz, Jean-Marc, Schambelan, Morris
• Format: Article
• Language: English
• Subjects: Adipose Tissue - drug effects; Adipose Tissue - metabolism; Biological and medical sciences; Body Composition - drug effects; Body Fat Distribution; Drug Combinations; Endocrinopathies; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; HIV Infections - blood; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - metabolism; HIV-1 - physiology; HIV-Associated Lipodystrophy Syndrome - blood; HIV-Associated Lipodystrophy Syndrome - drug therapy; HIV-Associated Lipodystrophy Syndrome - metabolism; Human immunodeficiency virus; Humans; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3 - administration & dosage; Insulin-Like Growth Factor Binding Protein 3 - adverse effects; Insulin-Like Growth Factor Binding Protein 3 - pharmacology; Insulin-Like Growth Factor I - administration & dosage; Insulin-Like Growth Factor I - adverse effects; Insulin-Like Growth Factor I - pharmacology; Lipid Metabolism - drug effects; Male; Medical sciences; Middle Aged; Obesity, Abdominal - blood; Obesity, Abdominal - drug therapy; Obesity, Abdominal - etiology; Obesity, Abdominal - metabolism; Original; Pilot Projects; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2009-2502

Context: HIV-infected patients on antiretroviral therapy are at increased risk for excess visceral adiposity and insulin resistance. Treatment with GH decreases visceral adiposity but worsens glucose metabolism. IGF-I, which mediates many of the effects of GH, improves insulin sensitivity in HIV-negative individuals. Objective: Our objective was to determine whether IGF-I, complexed to its major binding protein, IGF-binding protein-3 (IGFBP-3), improves glucose metabolism and alters body fat distribution in HIV-infected patients with abdominal obesity and insulin resistance. Methods: We conducted a pilot, open-label study in 13 HIV-infected men with excess abdominal adiposity and insulin resistance to assess the effect of 3 months of treatment with IGF-I/IGFBP-3 on glucose metabolism and fat distribution. Glucose metabolism was assessed by oral glucose tolerance test and hyperinsulinemic-euglycemic clamp. Endogenous glucose production (EGP), gluconeogenesis, whole-body lipolysis, and de novo lipogenesis (DNL) were measured with stable isotope infusions. Body composition was assessed by dual-energy x-ray absorptiometry and abdominal computed tomography scan. Results: Glucose tolerance improved and insulin-mediated glucose uptake increased significantly during treatment. EGP increased under fasting conditions, and suppression of EGP by insulin was blunted. Fasting triglycerides decreased significantly in association with a decrease in hepatic DNL. Lean body mass increased and total body fat decreased, whereas visceral adipose tissue did not change. Conclusions: Treatment with IGF-I/IGFBP-3 improved whole-body glucose uptake and glucose tolerance, while increasing hepatic glucose production. Fasting triglycerides improved, reflecting decreased DNL, and visceral adiposity was unchanged. IGF-I/IGFBP-3 treatment improved glucose tolerance and peripheral insulin sensitivity while increasing hepatic glucose production in HIV-infected men with insulin resistance.