TY - JOUR
T1 - InVitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease
T2 - A pilot study
AU - Kim, Roy J.
AU - Vaghani, Sumit
AU - Zifchak, Larisa M.
AU - Quinn, Joseph H.
AU - He, Weimian
AU - Tebas, Pablo
AU - Frank, Ian
N1 - Funding Information:
This work was supported by NIH K23 DK080644-01A1 (RK), the Penn Center for AIDS Research (NIH P30 AI 045008 ), and the Penn Clinical and Translational Science Award (NIH UL1RR024134 ). The lipoatrophy self-assessment instrument was kindly provided by Dr. Carl Grunfeld and was developed under “The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM)” funded by NIH Grants RO1-DK57508 and RO1-HL74814 . Mecasermin was provided at no cost by Tercica, Inc. SGBS cells were a generous gift from Dr. Martin Wabitsch. The investigators thank the staff of the Penn AIDS Clinical Trials Unit for their assistance.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - HIV
KW - IGF-I
KW - Lipoatrophy
KW - Lipodystrophy
KW - Mecasermin
UR - http://www.scopus.com/inward/record.url?scp=84883322675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84883322675&partnerID=8YFLogxK
U2 - 10.1016/j.arcmed.2013.06.001
DO - 10.1016/j.arcmed.2013.06.001
M3 - Article
C2 - 23867790
AN - SCOPUS:84883322675
SN - 0188-4409
VL - 44
SP - 361
EP - 369
JO - Archives of Medical Research
JF - Archives of Medical Research
IS - 5
ER -