Insulin therapy in pancreas and islet transplantation

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Pancreas and islet transplantation can be highly effective life-saving therapies in people with the most complex type 1 diabetes. Due to the shortage of organs for transplantation we urgently need to: a) improve methods for selecting good quality organs; and b) identify the best medical treatments to help transplants work well long-term.Donor insulin use as a marker of donor pancreas failureIt is imperative that organs selected for transplantation are of high quality, but current selection methods used by doctors could be improved. Selecting suboptimal organs for pancreas transplantation is partly why transplant failure rates are so high: 10-25% at 1 year and 30-60% at 5 years.Organs are available for transplantation when an organ donor dies on intensive care. In around half these individuals, blood sugar levels rise to abnormal levels. These high sugar levels are usually treated using insulin until the organs have been transplanted. I studied our patients in Manchester and showed that when insulin was given to pancreas donors on intensive care, the transplanted organs produced less insulin and were more likely to fail early (8.3%) compared to when the donor was not insulin-treated (1%). This could indicate that donor insulin use is a sign that the donor pancreas is damaged and that it is less suitable for transplantation. I plan to use information on 50,000 people who have previously received pancreas transplants to find out whether donor insulin use helps identify those organs that fail early. I expect to show that information on donor insulin use could improve the way that doctors select organs for pancreas transplantation and improve patient outcomes.In a laboratory-based study I will find out whether donor insulin use is a marker of death of insulin-producing cells (the beta cells of the pancreas). I will do this by using previously collected donor blood samples and by measuring DNA which leaks into the blood when beta-cells die. I will also see whether the donor insulin use is related to low levels of pancreatic function by measuring the amount of insulin produced by the donor pancreas. This study may provide laboratory-based evidence that donor insulin use is a marker of a failing pancreas.Insulin therapy to improve outcomes in islet and pancreas transplant recipientsAfter islet transplantation, intensive insulin therapy in recipients with type 1 diabetes is routine with the aim of achieving normal sugar levels during the hospital admission. However, it is unknown if the degree of sugar control is related to long-term islet transplant function. I plan to use previously collected patient data from the UK islet transplant consortium and relate the level of blood sugar control over five days post-transplant to the islet transplant function three months after transplant - as assessed by the insulin response to a standard meal. If positive, the study will support short-term use of insulin in the related situation of pancreas transplantation.In pancreas transplantation insulin therapy is not routinely given to recipients. In our experience, sugar levels are abnormal in 30% of patients immediately after pancreas transplantation - suggesting that the pancreas is not working properly and might benefit from insulin. I plan to look at the clinical and scientific evidence supporting insulin therapy after pancreas transplantation and discuss findings with a group of leading UK transplant surgeons. We will decide whether to perform a trial of insulin therapy in such patients and this will involve patient consultation. If evidence and opinion supports a trial, then I will design a feasibility study in Manchester and apply for research funding for the trial. If the evidence or opinion does not support a trial then I will lead the writing of a consensus statement that will describe best practice. This study has major potential to improve the care and long-term outcomes of patients undergoing pancreas transplantation.