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

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.

Recombinant human growth hormone and rosiglitazone for abdominal fat accumulation in HIV-infected patients with insulin resistance: a randomized, double-blind, placebo-controlled, factorial trial.

BACKGROUND: Recombinant human growth hormone (rhGH) reduces visceral adipose tissue (VAT) volume in HIV-infected patients but can worsen glucose homeostasis and lipoatrophy. We aimed to determine if adding rosiglitazone to rhGH would abrogate the adverse effects of rhGH on insulin sensitivity (SI) and subcutaneous adipose tissue (SAT) volume. METHODOLOGY/PRINCIPAL FINDINGS: Randomized, double-blind, placebo-controlled, multicenter trial using a 2×2 factorial design in which HIV-infected subjects with abdominal obesity and insulin resistance were randomized to rhGH 3 mg daily, rosiglitazone 4 mg twice daily, combination rhGH + rosiglitazone, or double placebo (control) for 12 weeks. The primary endpoint was change in SI by frequently sampled intravenous glucose tolerance test from entry to week 12. Body composition was assessed by whole body magnetic resonance imaging (MRI) and dual Xray absorptiometry (DEXA). Seventy-seven subjects were randomized of whom 72 initiated study drugs. Change in SI from entry to week 12 differed across the 4 arms by 1-way ANCOVA (P = 0.02); by pair-wise comparisons, only rhGH (decreasing SI; P = 0.03) differed significantly from control. Changes from entry to week 12 in fasting glucose and glucose area under the curve on 2-hour oral glucose tolerance test differed across arms (1-way ANCOVA P = 0.004), increasing in the rhGH arm relative to control. VAT decreased significantly in the rhGH arms (-17.5% in rhGH/rosiglitazone and -22.7% in rhGH) but not in the rosiglitazone alone (-2.5%) or control arms (-1.9%). SAT did not change significantly in any arm. DEXA results were consistent with the MRI data. There was no significant rhGH x rosiglitazone interaction for any body composition parameter. CONCLUSIONS/SIGNIFICANCE: The addition of rosiglitazone abrogated the adverse effects of rhGH on insulin sensitivity and glucose tolerance while not significantly modifying the lowering effect of rhGH on VAT. TRIAL REGISTRATION: Clinicaltrials.gov NCT00130286.

Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body composition in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effects of protease inhibitors (PIs) as antiretroviral therapy in comparison with other antiretroviral (non-PI) medications on glucose tolerance, lipid metabolism, and body fat distribution in human immunodeficiency virus (HIV)-infected young patients. METHODS: We conducted a cross-sectional clinical study in an outpatient HIV clinic. The study population consisted of 21 patients (15 female and 6 male) who had had at least 6 months of antiretroviral treatment. The mean age of the patients was 11.9 years (range, 6 to 16.5). RESULTS: Fifteen patients treated with PIs and 6 patients treated with non-PIs were enrolled in the study. We found no significant differences in the lipid panel and insulin resistance, as determined by using the Quantitative Insulin Sensitivity Check Index formula, in the PI group in comparison with the non-PI group. Lipodystrophy was observed in 47% (7 of 15) of the PI group and 33% (2 of 6) of the non-PI group (P = 0.66). In the presence of lipodystrophy, serum triglyceride levels were higher in the PI group than in the non-PI group (P = 0.046). No such difference was found between the treatment groups when no lipodystrophy was present. There was no significant difference in insulin resistance between the treatment groups in the presence or absence of lipodystrophy. CONCLUSION: Our study found the presence of lipodystrophy in HIV-infected young patients regardless of whether they were taking PIs or not. In the patients who had lipodystrophy, those treated with PIs had higher serum triglyceride levels than those not treated with PIs.