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

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 FiO(2) conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO(2) 21%) conditions or hypoxia (n = 12; FiO(2) 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O. 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