Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single‐blind cross‐over trial

High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol−1; aged 64.2 ± 9.4 years; four female] completed a single‐blind, randomised, sham‐controlled, cross‐over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}$] = 0.155; ∼2500 m simulated altitude) or normoxic conditions (FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}$ = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor‐1α]; [interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon‐like peptide‐1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect‐size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. Key points Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single‐blind, randomised sham‐controlled, cross‐over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin‐6]; [tumour necrosis factor‐α]; [interleukin‐10]) and