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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

Shepherd, AI, James, TJ, Gould, AAM, Mayes, H, Neal, R, Shute, J, Tipton, MJ, Massey, H, Saynor, ZL, Perissiou, M, Montgomery, H, Sturgess, C, Makaronidis, J, Murray, AJ, Grocott, MPW, Cummings, M, Young-Min, S, Rennell-Smyth, J, McNarry, MA, Mackintosh, KA , Dent, H, Robson, SC and Corbett, J (2024) 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. Journal of Physiology, 602 (21). pp. 5835-5854. ISSN 0022-3751

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Abstract

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 [(Formula presented.)] = 0.155; ∼2500 m simulated altitude) or normoxic conditions ((Formula presented.) = 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. (Figure presented.). 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 hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).

Item Type: Article
Uncontrolled Keywords: accelerometery; exercise mimetic; hypoxia; type 2 diabetes; weight loss; Humans; Diabetes Mellitus, Type 2; Inflammation; Blood Glucose; Cross-Over Studies; Single-Blind Method; Appetite; Aged; Middle Aged; Female; Male; Gastrointestinal Microbiome; Hypoxia; Glycemic Control; accelerometery; exercise mimetic; hypoxia; type 2 diabetes; weight loss; Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Female; Middle Aged; Male; Appetite; Cross-Over Studies; Single-Blind Method; Hypoxia; Aged; Glycemic Control; Inflammation; Blood Glucose; Clinical Trials and Supportive Activities; Diabetes; Nutrition; Behavioral and Social Science; Prevention; Obesity; Clinical Research; Metabolic and endocrine; Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Female; Middle Aged; Male; Appetite; Cross-Over Studies; Single-Blind Method; Hypoxia; Aged; Glycemic Control; Inflammation; Blood Glucose; 06 Biological Sciences; 11 Medical and Health Sciences; Physiology
Subjects: T Technology > TX Home economics > TX341 Nutrition. Foods and food supply
Q Science > QP Physiology
R Medicine > RC Internal medicine
Divisions: Sport and Exercise Sciences
Publisher: Wiley
SWORD Depositor: A Symplectic
Date Deposited: 17 Dec 2024 16:03
Last Modified: 17 Dec 2024 16:03
DOI or ID number: 10.1113/JP285322
URI: https://researchonline.ljmu.ac.uk/id/eprint/25112
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