{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T06:12:01Z","timestamp":1788588721884,"version":"build-2803163510"},"reference-count":72,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,11]]},"abstract":"Abstract<\/jats:title>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<\/jats:sub>): 61.1\u00a0\u00b1\u00a014.1\u00a0mmol\u00a0mol\u22121<\/jats:sup>; aged 64.2\u00a0\u00b1\u00a09.4\u00a0years; four female] completed a single\u2010blind, randomised, sham\u2010controlled, cross\u2010over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2<\/jats:sub> []\u00a0=\u00a00.155; \u223c2500\u00a0m simulated altitude) or normoxic conditions (\u00a0=\u00a00.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor\u20101\u03b1]; [interleukin\u20106]; [tumour necrosis factor\u2010\u03b1]; [interleukin\u201010]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2\u00a0h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon\u2010like peptide\u20101]); 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<\/jats:sub> and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P<\/jats:italic>\u00a0>\u00a00.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P<\/jats:italic>\u00a0=\u00a00.10; P<\/jats:italic>\u00a0=\u00a00.08 respectively) for a medium beneficial effect (d<\/jats:italic>\u00a0=\u00a00.49; d<\/jats:italic>\u00a0=\u00a00.59 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\u2010size for improved insulin sensitivity and reduced alpha diversity warrants further investigation.\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>Key points<\/jats:title>\nLiving 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.<\/jats:p><\/jats:list-item>\nIn a single\u2010blind, randomised sham\u2010controlled, cross\u2010over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2<\/jats:sub> \u223c0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin\u20106]; [tumour necrosis factor\u2010\u03b1]; [interleukin\u201010]) and hypoxic stress ([hypoxia inducible factor 1\u03b1]; heat shock protein 70]) in 13 adults with T2DM.<\/jats:p><\/jats:list-item>\nAppetite 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\u2010size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial.<\/jats:p><\/jats:list-item>\nHypoxic 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).<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp285322","type":"journal-article","created":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T05:00:30Z","timestamp":1716267630000},"page":"5835-5854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single\u2010blind cross\u2010over trial"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6392-7944","authenticated-orcid":false,"given":"Anthony I.","family":"Shepherd","sequence":"first","affiliation":[{"name":"Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health University of Portsmouth Portsmouth UK"},{"name":"Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health University of Portsmouth Portsmouth UK"},{"name":"Diabetes and Endocrinology Department Portsmouth Hospitals University NHS Trust Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1470-9400","authenticated-orcid":false,"given":"Thomas J.","family":"James","sequence":"additional","affiliation":[{"name":"Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health University of Portsmouth Portsmouth UK"},{"name":"Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health University of Portsmouth Portsmouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex A. 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