Beta-cell death and dysfunction drives hyperglycaemia in organ donors

Iestyn Shapey, Angela Summers, James O'Sullivan, Catherine Fullwood, Neil Hanley, John Casey, Shareen Forbes, Miranda Rosenthal, Paul RV Johnson, Pratik Choudhary, James Bushnell, James AM Shaw, Daniel Neiman , Ruth Shemer , Benjamin Glaser , Yuval Dor , Titus Augustine, Martin K. Rutter, David van Dellen

Research output: Contribution to journalArticlepeer-review


Donor hyperglycaemia following brain death has been attributed to reversible insulin resistance. However, our islet and pancreas transplant data suggests 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 (DBD).
In pancreas DBDs, 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 (miR375), as measures of beta-cell death. Relationships between markers of beta-cell death and islet isolation outcomes and post-transplant function were also evaluated.
Of 92 pancreas donors, 40 (43%) required insulin. Glycaemic control and beta-cell function were significantly poorer in IT donors vs. not-IT donors (median [IQR] peak glucose: 8 [7-11] vs. 6 [6-8] mmol/L, p=0.016; C-peptide: 3280 [3159-3386] vs. 3195 [2868-3386] pmol/L, p=0.046). IT donors had significantly higher levels of INS-cfDNA (35 [18-52] vs. 30 [8-51] copies/mL, p=0.035) and miR-375 (1.050 [0.19-1.95] vs. 0.73 [0.32-1.10] copies/nL, p=0.05). Circulating donor miR-375 was highly predictive of recipient islet graft failure at 3-months (aROC [SE] = 0.813 [0.149]).
In pancreas donors, hyperglycaemia requiring insulin therapy 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.
Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Publication statusAccepted/In press - 27 Jul 2023


  • Organ donor
  • insulin
  • beta-cell death
  • hyperglycaemia
  • glycaemic control
  • pancreas
  • islet
  • transplant


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