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: Adiponectin; HIV-1; Human growth hormone; Lipodystrophy; Rosiglitazone.

Figure 1

A. Change in Adiponectin by Study Arm; P = 0.0004 across treatment arms by Kruskal-Wallis test. Within arm changes: rhGH/rosiglitazone P = 0.0010; rosiglitazone P = 0.0073; rhGH P = 0.82; double placebo P = 0.27. Boxplots display the median (line inside box), first and third quartiles (lower and upper edges of box), mean (diamond), and whiskers (maximum and minimum observations aside from outliers). Open circles depict the individual data points. B. Change in C-reactive Protein by Study Arm; P = 0.74 across treatment arms by Kruskal-Wallis test. Within arm changes: rhGH/rosiglitazone P = 0.0001; rosiglitazone P = 0.012; rhGH P = 0.0078; double placebo P = 0.014.

Figure 1

A. Change in Adiponectin by Study Arm; P = 0.0004 across treatment arms by Kruskal-Wallis test. Within arm changes: rhGH/rosiglitazone P = 0.0010; rosiglitazone P = 0.0073; rhGH P = 0.82; double placebo P = 0.27. Boxplots display the median (line inside box), first and third quartiles (lower and upper edges of box), mean (diamond), and whiskers (maximum and minimum observations aside from outliers). Open circles depict the individual data points. B. Change in C-reactive Protein by Study Arm; P = 0.74 across treatment arms by Kruskal-Wallis test. Within arm changes: rhGH/rosiglitazone P = 0.0001; rosiglitazone P = 0.012; rhGH P = 0.0078; double placebo P = 0.014.