title: In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: a pilot study.
abstract: OBJECTIVE
  We tested the effects of recombinant insulin-like growth factor-I (IGF-I) in an adipocyte model of HIV lipodystrophy and in an open label study on body composition and metabolism in patients with HIV lipodystrophy.
  
  
  METHODS
  The effects of IGF-I on ritonavir-induced adipocyte cell death were studied in vitro. We assessed lipid accumulation, IGF signaling, apoptosis, and gene expression. We conducted a 24-week open label trial of recombinant IGF-I in ten adults with HIV associated lipoatrophy. Laboratory assessments included glucose, insulin, lipids, and IGF-I. At weeks 0 and 24, body composition studies were performed including skinfold measurement, dual-energy x-ray absorptiometry, and computed tomography of the abdomen and thigh.
  
  
  RESULTS
  In vitro, ritonavir increased delipidation and apoptosis of adipocytes, whereas co-treatment with IGF-I attenuated the effect. In the clinical study, subcutaneous adipose tissue did not increase in patients after treatment with IGF-I; however, there was a decrease in the proportion of abdominal fat (39.8 ± 7% vs. 34.6 ± 7%, p = 0.007). IGF-I levels increased with treatment (143 ± 28 μg/L at week 0 vs. 453 ± 212 μg/L at week 24, p = 0.002), whereas IGFBP-3 levels declined (3.554 ± 1.146 mg/L vs. 3.235 ± 1.151 mg/L, p = 0.02). Insulin at week 12 decreased significantly (90.1 ± 39.8 pmol/L vs. 33.2 ± 19.6 pmol/L, p = 0.002). There was a nonsignificant decrease in visceral adipose tissue (155.2 ± 68 cm² at week 0 vs. 140.6 ± 70 cm² at week 24, p = 0.08).
  
  
  CONCLUSIONS
  Use of recombinant IGF-I may lower fasting insulin and abdominal fat in patients with lipoatrophy associated with HIV infection. Further evaluation of this agent for treatment of HIV-associated lipodystrophy may be warranted.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: roy.kim@utsouthwestern.edu.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Kim
authors.forename: Sumit
authors.initials: S
authors.lastname: Vaghani
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Zifchak
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Quinn
authors.forename: Weimian
authors.initials: W
authors.lastname: He
authors.forename: Pablo
authors.initials: P
authors.lastname: Tebas
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects* / Q000473:pathology*; D050154:Adiposity / Q000187:drug effects* / Q000235:genetics; D001823:Body Composition / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D039682:HIV-Associated Lipodystrophy Syndrome / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; C065700:myotrophin; D007334:Insulin-Like Growth Factor I
keywords: HIV; IGF-I; Lipoatrophy; Lipodystrophy; Mecasermin