Effect of Recombinant Human Growth Hormone and Rosiglitazone for HIV-Associated Abdominal Fat Accumulation on Adiponectin and other Markers of Inflammation

Abstract

Background/Objective: In a previous report of HIV-infected patients with fat redistribution, we found that recombinant human growth hormone (rhGH) therapy reduced visceral adipose tissue (VAT) but increased insulin resistance, and that the addition of rosiglitazone reversed the negative effects of rhGH on insulin sensitivity. In this study, we sought to determine the effects of rhGH and rosiglitazone therapy on an array of inflammatory and fibrinolytic markers.

Methods: 72 patients with HIV-associated abdominal obesity and insulin resistance were randomized to treatment with rhGH, rosiglitazone, the combination of rhGH and rosiglitazone, or placebo for 12 weeks. Subjects with plasma and serum samples available at weeks 0 (n = 63) and 12 (n = 46–48) were assessed for adiponectin, C-reactive protein, homocysteine, interleukin-1, interleukin-6, tumor necrosis factor alpha, interferon gamma, fibrinogen, plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen.

Results: Treatment with both rosiglitazone alone and the combination of rosiglitazone and rhGH for 12 weeks resulted in significant increases in adiponectin levels from baseline. Adiponectin levels did not change significantly in the rhGH arm alone . There were no significant changes in the other biomarkers among the different treatment groups.

Discussion: In this study of HIV-infected patients with altered fat distribution, treatment with rosiglitazone had beneficial effects on adiponectin concentrations, an effect that was also seen with a combination of rosiglitazone and rhGH. RhGH administration alone, however, did not demonstrate any significant impact on adiponectin levels despite reductions in VAT.

Keywords:

• Lipodystrophy
• Adiponectin
• Rosiglitazone
• Human growth hormone
• HIV-1

Acknowledgments

The authors thank Franco Santiago for performance of biomarker assays.

Funding

This work was supported by the National Institutes of Health [grant number R01 DK065515], [grant number K24 AI078884], [grant number UL1 RR024996], [grant number M01 RR 00047], [grant number M01 RR 00645-27], [grant number UL1 TR000040-07], [grant number UL1 TR000457], [grant number P30 DK026687]. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. rhGH and rosiglitazone, with matching placebos, were generously donated by EMD Serono and GlaxoSmithKline, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosure Statement

MJG served as a consultant to EMD Serono on two occasions, most recently in 2007. His institution (Weill Cornell Medical College) received research support from EMD Serono for a clinical trial of rhGH for which he was the local principal investigator from 2004–2005. DPK and EE received research support from EMD Serono to their institution (St. Luke’s-Roosevelt Hospital) for a substudy of the present study (not reported herein). EE served as a consultant to Thera Technologies in 2010, which licensed tesamorelin to EMD Serono.