Toggle Main Menu Toggle Search

Open Access padlockePrints

Beta-cell death and dysfunction drives hyperglycaemia in organ donors

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.

Publication metadata

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

Pages: epub ahead of print

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


DOI: 10.1111/dom.15248

PubMed id: 37646197


Altmetrics provided by Altmetric


Funder referenceFunder name
Diabetes UK
Medical Research Council
NIHR Manchester Biomedical Research Centre
Royal College of Surgeons of Edinburgh