{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:04:47Z","timestamp":1784070287039,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T00:00:00Z","timestamp":1693353600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000692","name":"Royal College of Surgeons of Edinburgh","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","award":["NIHR203308"],"award-info":[{"award-number":["NIHR203308"]}],"id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggest that other mechanisms may be predominant. We aimed to determine the relationships between donor insulin use and markers of beta\u2010cell death and beta\u2010cell function in pancreas donors after brain death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In pancreas donors after brain death, we compared clinical and biochemical data in \u2018insulin\u2010treated\u2019 and \u2018not insulin\u2010treated donors\u2019 (IT vs. not\u2010IT). We measured plasma glucose, C\u2010peptide and levels of circulating unmethylated insulin gene promoter cell\u2010free DNA (\n                      <jats:italic>INS\u2010<\/jats:italic>\n                      cfDNA) and microRNA\u2010375 (miR\u2010375), as measures of beta\u2010cell death. Relationships between markers of beta\u2010cell death and islet isolation outcomes and post\u2010transplant function were also evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta\u2010cell function were significantly poorer in IT donors versus not\u2010IT donors [median (IQR) peak glucose: 8 (7\u201011) vs. 6 (6\u20108) mmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.016; C\u2010peptide: 3280 (3159\u20103386) vs. 3195 (2868\u20103386) pmol\/L,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.046]. IT donors had significantly higher levels of\n                      <jats:italic>INS<\/jats:italic>\n                      \u2010cfDNA [35 (18\u201052) vs. 30 (8\u201051) copies\/ml,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.035] and miR\u2010375 [1.050 (0.19\u20101.95) vs. 0.73 (0.32\u20101.10) copies\/nl,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.05]. Circulating donor miR\u2010375 was highly predictive of recipient islet graft failure at 3\u2009months [adjusted receiver operator curve (SE)\u2009=\u20090.813 (0.149)].\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta\u2010cell death. This provides an explanation for the relationship of donor IT with post\u2010transplant beta\u2010cell dysfunction in transplant recipients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15248","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T04:49:32Z","timestamp":1693370972000},"page":"3529-3537","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Beta\u2010cell death and dysfunction drives hyperglycaemia in organ donors"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3300-1053","authenticated-orcid":false,"given":"Iestyn M.","family":"Shapey","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Department of Renal and Pancreatic Transplantation Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Summers","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Department of Renal and Pancreatic Transplantation Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"O'Sullivan","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Foundation Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Fullwood","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Department of Research and Innovation (medical statistics) Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Casey","sequence":"additional","affiliation":[{"name":"Transplant Unit, Royal Infirmary of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareen","family":"Forbes","sequence":"additional","affiliation":[{"name":"Transplant Unit, Royal Infirmary of Edinburgh  Edinburgh UK"},{"name":"Endocrinology Unit, University of Edinburgh  Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Royal Free Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R. V.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratik","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Diabetes Research Group, King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Bushnell","sequence":"additional","affiliation":[{"name":"Richard Bright Renal Unit, Southmead Hospital  Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A. M.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Institute of Cellular Medicine Newcastle University  Newcastle UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Neiman","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel\u2010Canada The Hebrew University\u2010Hadassah Medical School  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Shemer","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel\u2010Canada The Hebrew University\u2010Hadassah Medical School  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Glaser","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Hadassah Medical Center and Faculty of Medicine Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Dor","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel\u2010Canada The Hebrew University\u2010Hadassah Medical School  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titus","family":"Augustine","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Department of Renal and Pancreatic Transplantation Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin K.","family":"Rutter","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Diabetes, Endocrinology and Metabolism Centre Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"van Dellen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Biology and Health University of Manchester  Manchester UK"},{"name":"Department of Renal and Pancreatic Transplantation Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-021-05411-9"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60553-5"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199308000-00022"},{"key":"e_1_2_11_5_1","first-page":"1","article-title":"Donor insulin use predicts beta\u2010cell function after islet transplantation","volume":"9","author":"Shapey IM","year":"2020","journal-title":"Diabetes Obes Metab"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0186480"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1519286113"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2017.02.043"},{"issue":"1","key":"e_1_2_11_9_1","first-page":"1","article-title":"The miRNA profile of human pancreatic islets and Beta\u2010cells and relationship to type 2 diabetes pathogenesis","volume":"8","author":"Bunt M","year":"2013","journal-title":"PloS One"},{"issue":"14","key":"e_1_2_11_10_1","article-title":"Multiplexing DNA methylation markers to detect circulating cell\u2010free DNA derived from human pancreatic \u03b2 cells.","volume":"5","author":"Neiman D","year":"2020","journal-title":"Insight"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3727\/215517911X617905"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.TP.0000100401.62912.B2"},{"key":"e_1_2_11_13_1","unstructured":"NHS Blood and Transplant. 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