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Context Aging is a primary risk factor for most chronic diseases, including type 2 diabetes. Both exercise and hypoxia regulate pathways that ameliorate age-associated metabolic muscle dysfunction. Objective We hypothesized that the combination of hypoxia and exercise would be more effective in improving glucose metabolism than normoxia exercise. Design and Participants We randomized 29 older sedentary individuals (62 ± 6 years; 14 women, 15 men) to bicycle exercise under normobaric hypoxia (fraction of inspired oxygen = 15%) or normoxia (fraction of inspired oxygen = 21%). Intervention Participants trained thrice weekly for 30 to 40 minutes over 8 weeks at a heart rate corresponding to 60% to 70% of peak oxygen update. Main Outcome Measures Insulin sensitivity measured by hyperinsulinemic-euglycemic glucose clamp and muscle protein expression before and after hyperinsulinemic-euglycemic glucose clamp. Results Heart rate and perceived exertion during training were similar between groups, with lower oxygen saturation when exercising under hypoxia (88.7 ± 1.5 vs 96.2 ± 1.2%, P &lt; 0.01). Glucose infusion rate after 8 weeks increased in both the hypoxia (5.7 ± 1.1 to 6.7 ± 1.3 mg/min/kg; P &lt; 0.01) and the normoxia group (6.2 ± 2.1 to 6.8 ± 2.1 mg/min/kg; P = 0.04), with a mean difference between groups of –0.44 mg/min/kg; 95% CI, –1.22 to 0.34; (P = 0.25). Markers of mitochondrial content and oxidative capacity in skeletal muscle were similar after training in both groups. Changes in Akt phosphorylation and glucose transporter 4 under fasting and insulin-stimulated conditions were not different between groups over time. Conclusions Eight weeks of hypoxia endurance training led to similar changes in insulin sensitivity and markers of oxidative metabolism compared with normoxia training. Normobaric hypoxia exercise did not enhance metabolic effects in sedentary older women and men beyond exercise alone.

Influences of Hypoxia Exercise on Whole-Body Insulin Sensitivity and Oxidative Metabolism in Older Individuals