Ten Nights of Moderate Hypoxia Improves Insulin Sensitivity in Obese Humans

Hypoxia in obese adipose tissue (AT) plays an important role in the development of whole-body insulin resistance by inducing local inflammation and the release of proinflammatory cytokines (1). Yet, living at high altitude is associated with a lower prevalence of impaired fasting glucose and type 2 diabetes compared with living at low altitude (2). Furthermore, exposure to hypoxic environments increases whole-body glucose fluxes in healthy males and glucose uptake in human and murine skeletal muscle (3). In addition, exercising under hypoxic conditions improves glucose tolerance more than exercising under normoxia (4), strongly suggesting an insulin-sensitizing effect of hypoxia. Therefore, we hypothesized that exposing obese men to 10 consecutive nights of moderate hypoxia (15 ± 0.5% O2, ∼2,400 m elevation) would improve insulin sensitivity. Eight healthy obese men (4 Caucasians, 3 African Americans, and 1 Hispanic of mean ± SEM age 28 ± 1 years, weight 96.5 ± 5.3 kg, and BMI 32.7 ± 1.3 kg/m2) without evidence of chronic disease or sleep apnea and taking no medication participated in this study. The protocol was approved by the institutional review board at Pennington Biomedical Research Center (Baton Rouge, LA). Subjects slept for 10 consecutive nights (∼10 h/night, ≥100 h in total) in a hypoxic tent (Hypoxico Inc., New York, NY) maintained at ∼15% O2 (range 14.5–15.5% O2, ∼2,400 m above sea level) using nitrogen dilution. Biopsies of abdominal subcutaneous AT and skeletal muscle were obtained at baseline and on day 11 under …