{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:21:55Z","timestamp":1792142515547,"version":"4.4.0"},"reference-count":41,"publisher":"American Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T00:00:00Z","timestamp":1492646400000},"content-version":"vor","delay-in-days":80,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","award":["BRF-2011-004"],"award-info":[{"award-number":["BRF-2011-004"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,5,1]]},"abstract":"<jats:p>Hypoglycemia is associated with increased cardiovascular mortality in trials of intensive therapy in type 2 diabetes mellitus (T2DM). We previously observed an increase in arrhythmias during spontaneous prolonged hypoglycemia in patients with T2DM. We examined changes in cardiac autonomic function and repolarization during sustained experimental hypoglycemia. Twelve adults with T2DM and 11 age- and BMI-matched control participants without diabetes underwent paired hyperinsulinemic clamps separated by 4 weeks. Glucose was maintained at euglycemia (6.0 mmol\/L) or hypoglycemia (2.5 mmol\/L) for 1 h. Heart rate, blood pressure, and heart rate variability were assessed every 30 min and corrected QT intervals and T-wave morphology every 60 min. Heart rate initially increased in participants with T2DM but then fell toward baseline despite maintained hypoglycemia at 1 h accompanied by reactivation of vagal tone. In control participants, vagal tone remained depressed during sustained hypoglycemia. Participants with T2DM exhibited greater heterogeneity of repolarization during hypoglycemia as demonstrated by T-wave symmetry and principal component analysis ratio compared with control participants. Epinephrine levels during hypoglycemia were similar between groups. Cardiac autonomic regulation during hypoglycemia appears to be time dependent. Individuals with T2DM demonstrate greater repolarization abnormalities for a given hypoglycemic stimulus despite comparable sympathoadrenal responses. These mechanisms could contribute to arrhythmias during clinical hypoglycemic episodes.<\/jats:p>","DOI":"10.2337\/db16-1310","type":"journal-article","created":{"date-parts":[[2017,1,31]],"date-time":"2017-01-31T02:10:34Z","timestamp":1485828634000},"page":"1322-1333","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":47,"title":["Cardiac Autonomic Regulation and Repolarization During Acute Experimental Hypoglycemia in Type 2 Diabetes"],"prefix":"10.2337","volume":"66","author":[{"given":"Elaine","family":"Chow","sequence":"first","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Bernjak","sequence":"additional","affiliation":[{"name":"INSIGNEO Institute for In Silico Medicine, University of Sheffield, Sheffield, U.K."},{"name":"Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Walkinshaw","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Lubina-Solomon","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Freeman","sequence":"additional","affiliation":[{"name":"Leeds Institute of Health Sciences, University of Leeds, Leeds, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian A.","family":"Macdonald","sequence":"additional","affiliation":[{"name":"School of Life Sciences, University of Nottingham, Nottingham, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2425-9565","authenticated-orcid":false,"given":"Simon R.","family":"Heller","sequence":"additional","affiliation":[{"name":"Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2017,1,30]]},"reference":[{"key":"2022031303333938300_B1","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1056\/NEJMoa0802987","article-title":"Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes","volume":"358","author":"Patel","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031303333938300_B2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1056\/NEJMoa0808431","article-title":"Glucose control and vascular complications in veterans with type 2 diabetes","volume":"360","author":"Duckworth","year":"2009","journal-title":"N Engl J Med"},{"key":"2022031303333938300_B3","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1056\/NEJMoa0802743","article-title":"Effects of intensive glucose lowering in type 2 diabetes","volume":"358","author":"Gerstein","year":"2008","journal-title":"N Engl J Med"},{"key":"2022031303333938300_B4","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1056\/NEJMoa1003795","article-title":"Severe hypoglycemia and risks of vascular events and death","volume":"363","author":"Zoungas","year":"2010","journal-title":"N Engl J Med"},{"key":"2022031303333938300_B5","doi-asserted-by":"crossref","first-page":"3137","DOI":"10.1093\/eurheartj\/eht332","article-title":"Does hypoglycaemia increase the risk of cardiovascular events? 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