Insulin therapy as a marker of beta-cell death in pancreas donors

Principal Investigator – Iestyn Shapey

Pancreas transplantation is a highly effective life-saving therapy in complex type 1 Diabetes and allows patients to produce their own insulin. Due to the well-documented shortage of organs for transplantation, there is an urgent need to improve methods for selecting good quality organs.
It is imperative that the organs selected for transplantation are of the highest quality possible, but there is currently no reliable way of assessing their suitability. Inappropriate donor organ selection impacts significantly on eventual outcomes from pancreas transplantation – 3 out of 10 grafts fail at 5 years.

When a patient’s brain dies, organ donation and transplantation becomes a possibility, but the hormone levels in the body can become imbalanced and potentially damage organs offered for transplantation. Replacement of hormones in organ donors is routine practice in intensive care units, and insulin may be given to stabilise glucose levels. In our experience, when insulin is given to donors, the pancreas does not always work immediately after transplantation and short-term outcomes are worse.

The need for insulin is a sign that the pancreas is not working properly. However, it is unclear whether insulin therapy in organ donors is a sign of damage to the pancreas (cell death) or a short-term response to brain death (cell stress). Distinguishing between cell death and stress is important and would support the idea that insulin therapy in donors helps predict poor outcome. It is possible to measure the DNA from insulin producing beta-cells which are shed into the blood when they die. I aim to describe the relationships between insulin therapy in donors, beta-cell function (c-peptide) and beta-cell death (circulating cell-free DNA) for the first time using samples from a group of pancreas donors. This would help to decide which organs to transplant, and which organs may require additional support after transplantation.