Insulin Use on Intensive Care Units as a Marker of beta-Cell Death in Brain Dead Pancreas Donors
1Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, United Kingdom
2Department of Renal and Pancreatic Transplantation, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Meeting: 2018 American Transplant Congress
Abstract number: A337
Session Information
Session Name: Poster Session A: Pancreas and Islet: All Topics
Session Type: Poster Session
Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Introduction
Objective methods for assessing the quality of pancreata for transplantation are urgently required. Donors after brain death (DBD) experience a catecholamine storm and systemic inflammation, which may result in pancreatic damage. We hypothesized that donors requiring insulin (+IN) experience a pro-apoptotic state culminating in beta-cell death.
Methods
Plasma samples from DBDs +IN (n = 6) and -IN (n = 4) were collected at two time-points (TP): 1) at the time of consent for organ donation; and 2) 24hrs later at aortic cross clamp during organ procurement. miRNA levels, assessed by PCR, were compared between groups and TPs.
Results
miR-375 (a marker of beta-cell death) was down-regulated -2.5 fold comparing +IN vs. –IN at TP1, but up-regulated +4-fold at TP2 (p=0.027). When comparing TP2 vs. TP1, in the +IN cohort, miR-375 was unchanged between the time-points, whereas in the -IN cohort, miR-375 was down-regulated -8-fold (p=0.008).
In +IN compared to –IN donors, levels of the pro-apoptotic miR-34a showed a trend to down-regulation -12-fold (p=0.212) at TP1, but up-regulation +6-fold at TP2 (p=0.349). Similarly, miRs 26a (regulates insulin production) were up-regulated +40-fold (p=0.252) at TP1, but down-regulated -7-fold (p=0.191) at TP2 (p=0.184).
Conclusions
Greater expression of miR-375 in +IN donors compared to –IN donors suggests higher and persistent levels of beta-cell death in +IN donors. In –IN donors, a reduction in miR-375 24 hours later is in keeping with recovery from brain death related beta-cell stress. Donor insulin use may therefore be a surrogate of beta-cell death potentially predicting adverse outcomes.
CITATION INFORMATION: Shapey M., Summers A., O'Sullivan J., Yianoullou P., Augustine T., Rutter M., van Dellen D. Insulin Use on Intensive Care Units as a Marker of beta-Cell Death in Brain Dead Pancreas Donors Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Shapey M, Summers A, O'Sullivan J, Yianoullou P, Augustine T, Rutter M, Dellen Dvan. Insulin Use on Intensive Care Units as a Marker of beta-Cell Death in Brain Dead Pancreas Donors [abstract]. https://atcmeetingabstracts.com/abstract/insulin-use-on-intensive-care-units-as-a-marker-of-beta-cell-death-in-brain-dead-pancreas-donors/. Accessed October 11, 2024.« Back to 2018 American Transplant Congress