Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial

Abstract

Background: Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome.

Methods: In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO₂ conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO₂ 21%) conditions or hypoxia (n = 12; FiO₂ 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O_2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues.

Results: The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISI_Clamp: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg^-1 *min^-1/(mU* l^-1); p = 0.767). In contrast, ISI_Clamp improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg^-1 *min^-1/(mU *l^-1); p < 0.05). Between group comparison of ISI_Clamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISI_Clamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISI_Clamp during hypoxic training.

Conclusions: Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.