The impact of hypoxia exposure on glucose homeostasis in metabolically compromised humans: A systematic review

Humans living at a higher altitude are less prone to suffer from impaired glucose homeostasis and type 2 diabetes mellitus (T2DM), which might at least partly be explained by lower oxygen availability at higher altitudes. The present systematic review aimed to provide an overview of the current literature on the effects of hypoxia exposure on glucose homeostasis in metabolically compromised humans. Several databases were searched up to August 10^th, 2020. The search strategy identified 368 unique records. Following assessment for eligibility based on the selection criteria, 16 studies were included in this review. Six studies (2 controlled studies; 4 uncontrolled studies) demonstrated beneficial effects of hypoxia exposure on glucose homeostasis, while 10 studies (8 controlled studies; 2 uncontrolled studies) reported no improvement in glucose homeostasis following hypoxia exposure. Notably, passive hypoxia exposure seemed to improve glucose homeostasis, whereas hypoxic exercise training (2–8 weeks) appeared to have no additional/synergistic effects on glucose homeostasis compared to normoxia exposure. Due to the heterogeneity in study populations and intervention duration (acute studies / 2–8 wks training), it is difficult to indicate which factors may explain conflicting study outcomes. Moreover, these results should be interpreted with some caution, as several studies did not include a control group. Taken together, hypoxia exposure under resting and exercise conditions might provide a novel therapeutic strategy to improve glucose homeostasis in metabolically compromised individuals, but more randomized controlled trials are warranted before strong conclusions on the effects of hypoxia exposure on glucose homeostasis can be drawn.