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

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.

Reduced diastolic function and left ventricular mass in HIV-negative preadolescent children exposed to antiretroviral therapy in utero.

OBJECTIVE: Abnormalities in left ventricular morphology and function have been reported in HIV-negative infants exposed to antiretroviral therapy (ART) in utero that persists throughout preschool age. The objective of this study was to determine if these abnormalities persist, resolve, or worsen during preadolescence. DESIGN: Cross-sectional observation study. METHODS: Thirty HIV-negative children born to HIV-positive women and exposed to ART in utero (mean age 8 ± 2 years, 37% female, 74% African-American) and 30 HIV-negative children born to HIV-negative women (mean age 8 ± 3 years, 37% female, 76% African-American) underwent two-dimensional Doppler, tissue Doppler, and strain echocardiography to evaluate left ventricular systolic and diastolic function. RESULTS: Weight, body surface area, heart rate and blood pressure were similar between groups. For the ART-exposed group, left ventricular mass index was lower (60 ± 9 vs. 67 ± 12 g/m, P < 0.02) and early diastolic annular velocity was lower (15.0 ± 2.2 vs. 16.3 ± 2.5 cm/s, P < 0.03) compared to controls. Left ventricular systolic function did not differ between groups. Lower maternal third trimester CD4 count was associated with lower early diastolic annular velocity; other non-HIV-related variables including cocaine use and increased maternal age correlated with lower left ventricular mass index. CONCLUSIONS: Abnormalities in left ventricular systolic performance previously reported in HIV-negative infants and preschool aged children exposed to ART in utero were not apparent in preadolescent children. Left ventricular diastolic relaxation was reduced compared with controls suggesting residual effects of ART exposure on left ventricular diastolic function. Larger, longitudinal studies are necessary to confirm these observations.