InVitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: A pilot study

Roy J. Kim, Sumit Vaghani, Larisa M. Zifchak, Joseph H. Quinn, Weimian He, Pablo Tebas, Ian Frank

Research output: Contribution to journalArticle

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Abstract

Background and Aims: 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 invitro. 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: Invitro, 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.

Original languageEnglish (US)
Pages (from-to)361-369
Number of pages9
JournalArchives of Medical Research
Volume44
Issue number5
DOIs
StatePublished - Jul 2013

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Metabolic Diseases
Adiposity
Insulin-Like Growth Factor I
HIV
Adipocytes
Lipodystrophy
Ritonavir
Abdominal Fat
Insulin
Body Composition
HIV-Associated Lipodystrophy Syndrome
Apoptosis
Insulin-Like Growth Factor Binding Protein 3
Intra-Abdominal Fat
Subcutaneous Fat
Therapeutics
Thigh
Abdomen
HIV Infections
Fasting

Keywords

  • HIV
  • IGF-I
  • Lipoatrophy
  • Lipodystrophy
  • Mecasermin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

InVitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease : A pilot study. / Kim, Roy J.; Vaghani, Sumit; Zifchak, Larisa M.; Quinn, Joseph H.; He, Weimian; Tebas, Pablo; Frank, Ian.

In: Archives of Medical Research, Vol. 44, No. 5, 07.2013, p. 361-369.

Research output: Contribution to journalArticle

Kim, Roy J. ; Vaghani, Sumit ; Zifchak, Larisa M. ; Quinn, Joseph H. ; He, Weimian ; Tebas, Pablo ; Frank, Ian. / InVitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease : A pilot study. In: Archives of Medical Research. 2013 ; Vol. 44, No. 5. pp. 361-369.
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