Defining the link between peri-transplant hyperglycaemia, inflammation, and graft survival in pancreas transplantation for type 1 diabetes.

Background Pancreas transplantation (PT) can offer life-extending and quality-of-life benefits for patients with uncontrolled type 1 diabetes and kidney failure, however early graft failure remains a significant challenge. Postoperative hyperglycaemia is associated with a threefold increased risk of pancreas failure within three years, though causality is undefined. Hyperglycaemia-driven inflammation may underlie such inferior outcomes. Aim We aim to define the mechanistic relationship between peri-transplant hyperglycaemia, inflammation, and pancreas graft survival in donors and recipients using existing resources. Methods Work Package 1 will retrospectively analyse data from all PT recipients at Manchester Royal Infirmary (2017–2024) assessing associations between postoperative blood glucose, inflammatory markers (lipase and CRP), and graft survival. Statistical modelling will evaluate the predictive value of hyperglycaemia on inflammation and graft failure. Work Package 2 will characterise the inflammatory profile of deceased pancreas donors using serum samples from the QUOD biobank. Luminex and colorimetric assays will quantify cytokines and oxidative stress markers to determine associations with donor non-diabetic hyperglycaemia and graft survival. Outputs Demonstrating mechanistic links between hyperglycaemia, inflammation, and pancreas transplant failure, would provide novel therapeutic targets and biochemical predictors of transplant survival, improving pancreas transplant longevity and extending diabetes cure for this cohort of patients with diabetes.