Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

Abstract

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5-2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation.

Trial registration: ClinicalTrials.gov NCT00639457.

Figures

Fig. 1.

Baseline and postintervention (A) basal and insulin-mediated (Hyper-Ins) peripheral glucose disposal rate (glucose Rd; means ± SE). Basal hepatic insulin sensitivity index (B) and the ability of hyperinsulinemia (280–350 pM) to suppress endogenous glucose production rate (Ra; C) were quantified using the hyperinsulinemic euglycemic clamp procedure with [6,6-2H2]glucose tracer infusion in HIV-infected adults (n = 39) with baseline insulin resistance and central adiposity. A: peripheral glucose disposal was improved in both groups (*P ≤ 0.0002), but more (§P = 0.005) in the pioglitazone plus exercise training group (pio + ex) than in the pioglitazone group (pio). B: hepatic insulin sensitivity. C: insulin's ability to suppress endogenous glucose production rate improved equivalently (*P < 0.03) in both groups after intervention.