Document Detail


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.
MedLine Citation:
PMID:  20610601     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Madhu N Rao; Kathleen Mulligan; Viva Tai; Michael J Wen; Artem Dyachenko; Melissa Weinberg; Xiaojuan Li; Thomas Lang; Carl Grunfeld; Jean-Marc Schwarz; Morris Schambelan
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-07
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2010-09-28     Revised Date:  2011-09-13    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4361-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. madhu.rao@ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue / drug effects,  metabolism
Body Composition / drug effects
Body Fat Distribution*
Drug Combinations
Glucose / metabolism*
HIV Infections / blood,  complications,  drug therapy*,  metabolism
HIV-1 / physiology
HIV-Associated Lipodystrophy Syndrome / blood,  drug therapy,  metabolism
Humans
Insulin Resistance*
Insulin-Like Growth Factor Binding Protein 3 / administration & dosage*,  adverse effects,  pharmacology
Insulin-Like Growth Factor I / administration & dosage*,  adverse effects,  pharmacology
Lipid Metabolism / drug effects
Male
Middle Aged
Obesity, Abdominal / blood,  drug therapy*,  etiology,  metabolism
Pilot Projects
Grant Support
ID/Acronym/Agency:
DK54615/DK/NIDDK NIH HHS; DK66999/DK/NIDDK NIH HHS; DK69185/DK/NIDDK NIH HHS; RR00083/RR/NCRR NIH HHS; RR24131/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Drug Combinations; 0/Insulin-Like Growth Factor Binding Protein 3; 50-99-7/Glucose; 67763-96-6/Insulin-Like Growth Factor I
Comments/Corrections

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