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Lookup NU author(s): Professor James Shaw
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.Background: 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-cell death and beta-cell function in pancreas donors after brain death. Methods: In pancreas donors after brain death, we compared clinical and biochemical data in ‘insulin-treated’ and ‘not insulin-treated donors’ (IT vs. not-IT). We measured plasma glucose, C-peptide and levels of circulating unmethylated insulin gene promoter cell-free DNA (INS-cfDNA) and microRNA-375 (miR-375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated. Results: Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors versus not-IT donors [median (IQR) peak glucose: 8 (7-11) vs. 6 (6-8) mmol/L, p =.016; C-peptide: 3280 (3159-3386) vs. 3195 (2868-3386) pmol/L, p =.046]. IT donors had significantly higher levels of INS-cfDNA [35 (18-52) vs. 30 (8-51) copies/ml, p =.035] and miR-375 [1.050 (0.19-1.95) vs. 0.73 (0.32-1.10) copies/nl, p =.05]. Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3 months [adjusted receiver operator curve (SE) = 0.813 (0.149)]. Conclusions: In pancreas donors, hyperglycaemia requiring IT is strongly associated with beta-cell death. This provides an explanation for the relationship of donor IT with post-transplant beta-cell dysfunction in transplant recipients.
Author(s): Shapey IM, Summers A, O'Sullivan J, Fullwood C, Hanley NA, Casey J, Forbes S, Rosenthal M, Johnson PRV, Choudhary P, Bushnell J, Shaw JAM, Neiman D, Shemer R, Glaser B, Dor Y, Augustine T, Rutter MK, van Dellen D
Publication type: Article
Publication status: Published
Journal: Diabetes, Obesity and Metabolism
Year: 2023
Volume: 25
Issue: 12
Pages: 3529-3537
Print publication date: 01/12/2023
Online publication date: 30/08/2023
Acceptance date: 27/07/2023
Date deposited: 26/09/2023
ISSN (print): 1462-8902
ISSN (electronic): 1463-1326
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1111/dom.15248
DOI: 10.1111/dom.15248
Data Access Statement: Raw data for miR and cfDNA is provided in the supplementary tables. All other data is reported in the article.
PubMed id: 37646197
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