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However, the degree to which the methodology of clamp studies is standardised is unclear. This systematic review examines how hyperinsulinaemic\u2013hypoglycaemic clamps have been performed and elucidates potential important differences.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A literature search in PubMed and EMBASE was conducted. Articles in English published between 1980 and 2018, involving adults with or without diabetes, were included.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>A total of 383 articles were included. There was considerable variation in essential methodology of the hypoglycaemic clamp procedures, including the insulin dose used (49-fold difference between the lowest and the highest rate), the number of hypoglycaemic steps (range 1\u22126), the hypoglycaemic nadirs (range 2.0\u20134.3\u00a0mmol\/l) and the duration (ranging from 5 to 660\u00a0min). Twenty-seven per cent of the articles reported whole blood glucose levels, most venous levels. In 70.8% of the studies, a dorsal hand vein was used for blood sampling, with some form of hand warming to arterialise venous blood in 78.8% of these. Key information was missing in 61.9% of the articles.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>Although the hyperinsulinaemic\u2013hypoglycaemic clamp procedure is considered the gold standard to study experimental hypoglycaemia, a uniform standard with key elements on how to perform these experiments is lacking. Methodological differences should be considered when comparing results between hypoglycaemic clamp studies.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>PROSPERO registration<\/jats:title>\n                <jats:p>This systematic review is registered in PROSPERO (CRD42019120083).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-020-05361-8","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T07:51:10Z","timestamp":1612943470000},"page":"727-736","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Hyperinsulinaemic\u2013hypoglycaemic glucose clamps in human research: a systematic review of the literature"],"prefix":"10.1007","volume":"64","author":[{"name":"on behalf of the Hypo-RESOLVE consortium","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6344-5408","authenticated-orcid":false,"given":"Therese W.","family":"Fabricius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9905-7669","authenticated-orcid":false,"given":"Clementine E. 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