Use of recombinant IGF-I lowers fasting insulin and abdominal fat in patients

[h=1]In vitro and in vivo effects of IGF-I on adiposity in HIV-associated metabolic disease: a pilot study.[/h]Kim RJ1, Vaghani S, Zifchak LM, Quinn JH, He W, Tebas P, Frank I.
[h=3]Author information[/h]

[h=3]Abstract[/h][h=4]BACKGROUND AND AIMS:[/h]<abstracttext label="BACKGROUND AND AIMS" nlmcategory="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.</abstracttext>
[h=4]METHODS:[/h]<abstracttext label="METHODS" nlmcategory="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.</abstracttext>
[h=4]RESULTS:[/h]<abstracttext label="RESULTS" nlmcategory="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).</abstracttext>
[h=4]CONCLUSIONS:[/h]<abstracttext label="CONCLUSIONS" nlmcategory="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.</abstracttext>

[h=1]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.[/h]Rao MN1, Mulligan K, Tai V, Wen MJ, Dyachenko A, Weinberg M, Li X, Lang T, Grunfeld C, Schwarz JM, Schambelan M.
[h=3]Author information[/h]

[h=3]Abstract[/h][h=4]CONTEXT:[/h]<abstracttext label="CONTEXT" nlmcategory="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.</abstracttext>
[h=4]OBJECTIVE:[/h]<abstracttext label="OBJECTIVE" nlmcategory="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.</abstracttext>
[h=4]METHODS:[/h]<abstracttext label="METHODS" nlmcategory="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.</abstracttext>
[h=4]RESULTS:[/h]<abstracttext label="RESULTS" nlmcategory="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.</abstracttext>
[h=4]CONCLUSIONS:[/h]<abstracttext label="CONCLUSIONS" nlmcategory="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.</abstracttext>