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As there is previous evidence for the relevance of sleep in metabolic control, we assessed the acute contribution of sleep to the counterregulatory adaptation to recurrent hypoglycaemia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Within a balanced crossover design, 15 healthy, normal-weight male participants aged 18\u201335\u00a0years underwent three hyperinsulinaemic\u2013hypoglycaemic clamps with a glucose nadir of 2.5\u00a0mmol\/l, under two experimental conditions, sleep and sleep deprivation. Participants were exposed to two hypoglycaemic episodes, followed by a third hypoglycaemic clamp after one night of regular 8\u00a0h sleep vs sleep deprivation. The counterregulatory response of relevant hormones (glucagon, growth hormone [GH], ACTH, cortisol, adrenaline [epinephrine] and noradrenaline [norepinephrine]) was measured, and autonomic and neuroglycopenic symptoms were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Sleep deprivation compared with sleep dampened the adaptation to recurrent hypoglycaemia for adrenaline (<jats:italic>p<\/jats:italic>=0.004), and this pattern also emerged in an overall analysis including adrenaline, GH and glucagon (<jats:italic>p<\/jats:italic>=0.064). After regular sleep, the counterregulatory responses of adrenaline (<jats:italic>p<\/jats:italic>=0.005), GH (<jats:italic>p<\/jats:italic>=0.029) and glucagon (<jats:italic>p<\/jats:italic>=0.009) were attenuated during the 3rd clamp compared with the 1st clamp, but were preserved after sleep deprivation (all <jats:italic>p<\/jats:italic>&gt;0.225). Neuroglycopenic and autonomic symptoms during the 3rd clamp compared with the 1st clamp were likewise reduced after sleep (<jats:italic>p<\/jats:italic>=0.005 and <jats:italic>p<\/jats:italic>=0.019, respectively). In sleep deprivation, neuroglycopenic symptoms increased (<jats:italic>p<\/jats:italic>=0.014) and autonomic symptoms were unchanged (<jats:italic>p<\/jats:italic>=0.859).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>The counterregulatory adaptation to recurrent hypoglycaemia is compromised by sleep deprivation between hypoglycaemic episodes, indicating that sleep is essential for the formation of a neurometabolic memory, and may be a potential target of interventions to treat hypoglycaemia unawareness syndrome.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-022-05702-9","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T14:03:12Z","timestamp":1650549792000},"page":"1212-1221","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sleep deprivation prevents counterregulatory adaptation to recurrent hypoglycaemia"],"prefix":"10.1007","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-7022","authenticated-orcid":false,"given":"Svenja","family":"Meyh\u00f6fer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Dembinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schultes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Born","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Wilms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Lehnert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Hallschmid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2034-5922","authenticated-orcid":false,"given":"Sebastian M.","family":"Meyh\u00f6fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,21]]},"reference":[{"issue":"22","key":"5702_CR1","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.1056\/NEJMra031354","volume":"350","author":"PE Cryer","year":"2004","unstructured":"Cryer PE (2004) Diverse causes of hypoglycemia-associated autonomic failure in diabetes. 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