{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:22:21Z","timestamp":1792142541598,"version":"4.4.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>A non-randomized, mechanistic intervention study.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Insulin-treated patients with type 2 diabetes (<jats:italic>n<\/jats:italic>\u2009= 21, age (mean \u00b1 <jats:sc>s.d.)<\/jats:sc>: 62.8 \u00b1 6.5 years, BMI: 29.0 \u00b1 4.2 kg\/m<jats:sup>2<\/jats:sup>, HbA1c: 6.8 \u00b1 0.5% (51.0 \u00b1 5.4 mmol\/mol)) and matched controls (<jats:italic>n<\/jats:italic>\u2009= 21, age: 62.2 \u00b1 8.3 years, BMI 29.2 \u00b1 3.5 kg\/m<jats:sup>2<\/jats:sup>, HbA1c: 5.3 \u00b1 0.3% (34.3 \u00b1 3.3 mmol\/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol\/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose &lt; 3.0 mmol\/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Both groups experienced progressively increasing heart rate corrected QT (Fridericia\u2019s formula) interval prolongations during hypoglycemia ((\u2206mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (<jats:italic>P<\/jats:italic> = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (<jats:italic>P<\/jats:italic> = 0.033 and <jats:italic>P<\/jats:italic> &lt; 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0232","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T12:42:23Z","timestamp":1622810543000},"page":"343-353","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":23,"title":["Acute hypoglycemia and risk of cardiac arrhythmias in insulin-treated type 2 diabetes and controls"],"prefix":"10.1093","volume":"185","author":[{"given":"Andreas","family":"Andersen","sequence":"first","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark"},{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonatan I","family":"Bagger","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark"},{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P A","family":"Baldassarre","sequence":"additional","affiliation":[{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"3Department of Medicine and Aging Sciences, G. d\u2019Annunzio University, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikkel B","family":"Christensen","sequence":"additional","affiliation":[{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"4Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten U","family":"Abelin","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark"},{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Faber","sequence":"additional","affiliation":[{"name":"5Department of Medicine, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Pedersen-Bjergaard","sequence":"additional","affiliation":[{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"7Department of Endocrinology and Nephrology, Nordsj\u00e6llands Hospital Hiller\u00f8d, University of Copenhagen, Hiller\u00f8d, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens J","family":"Holst","sequence":"additional","affiliation":[{"name":"8Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"9Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi B","family":"Lindhardt","sequence":"additional","affiliation":[{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"10Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Gislason","sequence":"additional","affiliation":[{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"10Department of Cardiology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"11The Danish Heart Foundation, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip K","family":"Knop","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark"},{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"},{"name":"9Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Vilsb\u00f8ll","sequence":"additional","affiliation":[{"name":"1Steno Diabetes Center Copenhagen, Gentofte Hospital, Hellerup, Denmark"},{"name":"2Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark"},{"name":"6Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/2\/EJE-21-0232.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/2\/EJE-21-0232.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:29Z","timestamp":1676391389000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/2\/343\/6654320"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0232","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,1]]}}}