title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. madhu.rao@ucsf.edu
authors.forename: Madhu N
authors.initials: MN
authors.lastname: Rao
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mulligan
authors.forename: Viva
authors.initials: V
authors.lastname: Tai
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Wen
authors.forename: Artem
authors.initials: A
authors.lastname: Dyachenko
authors.forename: Melissa
authors.initials: M
authors.lastname: Weinberg
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Li
authors.forename: Thomas
authors.initials: T
authors.lastname: Lang
authors.forename: Carl
authors.initials: C
authors.lastname: Grunfeld
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Schwarz
authors.forename: Morris
authors.initials: M
authors.lastname: Schambelan
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D050218:Body Fat Distribution; D004338:Drug Combinations; D005947:Glucose / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D039682:HIV-Associated Lipodystrophy Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010865:Pilot Projects
chemical_list: D004338:Drug Combinations; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D005947:Glucose