Insulin resistance in HIV-infected youth is associated with decreased mitochondrial respiration

Objective: To identify relationships between insulin resistance (IR) and mitochondrial respiration in perinatally HIV-infected youth. Design: Case-control study. Methods: Mitochondrial respiration was assessed in perinatally HIV-infected youth in Tanner stages 2-5, 25 youth with IR (IR) and 50 without IR (IR) who were enrolled in the Pediatric HIV/AIDS Cohort Study. IR was defined as a homeostatic model of assessment for IR value at least 4.0. A novel, high-throughput oximetry method was used to evaluate cellular respiration in peripheral blood mononuclear cells. Unadjusted and adjusted differences in mitochondrial respiration markers between IR and IR were evaluated, as were correlations between mitochondrial respiration markers and biochemical measurements. Results: IR and IR youth were similar on age, sex, and race/ethnicity. Mean age was 16.5 and 15.6 years in IR and IR, respectively. The IR group had significantly higher mean BMI and metabolic analytes (fasting glucose, insulin, cholesterol, triglycerides, and venous lactate and pyruvate) compared with the IR. Mitochondrial respiration markers were, on average, lower in the IR compared with IR, including basal respiration (417.5 vs. 597.5 pmol, P0.074), ATP production (11 513 vs. 15 202 pmol, P0.078), proton leak (584.6 vs. 790.0 pmol, P0.033), maximal respiration (1815 vs. 2399 pmol, P0.025), and spare respiration capacity (1162 vs. 2017 pmol, P0.032). Nonmitochondrial respiration did not differ by IR status. The results did not change when adjusted for age. Conclusion: HIV-infected youth with IR have lower mitochondrial respiration markers when compared to youth without IR. Disordered mitochondrial respiration may be a potential mechanism for IR in this population.