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Insulin therapy in pancreas and islet transplantation

胰腺和胰岛移植中的胰岛素治疗

基本信息

批准号：
MR/P019250/1
负责人：
Iestyn Shapey
金额：
$ 26.09万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FP019250%2F1
关键词：
Insulin therapy pancreas islet transplantation

项目摘要

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.

胰腺和胰岛移植可以是最复杂的1型糖尿病患者的高效救生疗法。由于移植器官的短缺，我们迫切需要：a）改进选择高质量器官的方法;和B）确定最佳的医学治疗方法，以帮助移植长期良好地工作。供体胰岛素的使用作为供体胰腺衰竭的标志选择用于移植的器官必须是高质量的，但目前医生使用的选择方法可以改进。选择次优器官进行胰腺移植是移植失败率如此之高的部分原因：1年为10-25%，5年为30-60%。当器官捐献者在重症监护期间死亡时，器官可用于移植。在大约一半的人中，血糖水平上升到异常水平。这些高糖水平通常使用胰岛素治疗，直到器官移植。我研究了我们在曼彻斯特的患者，结果表明，与未接受胰岛素治疗的供体（1%）相比，在重症监护下给予胰腺供体胰岛素时，移植器官产生的胰岛素较少，并且更有可能早期失败（8.3%）。这可能表明供体胰岛素的使用是供体胰腺受损的一个迹象，并且它不太适合移植。我计划使用5万名以前接受过胰腺移植的人的信息，以了解供体胰岛素的使用是否有助于识别早期衰竭的器官。我希望通过实验室研究发现，供体胰岛素的使用是否是产生胰岛素的细胞（胰腺β细胞）死亡的标志。我将通过使用以前收集的供体血液样本和测量当β细胞死亡时泄漏到血液中的DNA来完成这一工作。我还将通过测量供体胰腺产生的胰岛素量来观察供体胰岛素的使用是否与胰腺功能低下有关。这项研究可能提供基于实验室的证据，供体胰岛素的使用是一个失败的pancreat.Insulin治疗，以改善胰岛和胰腺移植previentsAfter胰岛移植的结果，强化胰岛素治疗1型糖尿病受者是常规的，目的是在入院期间达到正常的血糖水平。然而，尚不清楚糖控制程度是否与长期胰岛移植功能有关。我计划使用之前从英国胰岛移植联盟收集的患者数据，并将移植后5天的血糖控制水平与移植后3个月的胰岛移植功能相关联-通过对标准餐的胰岛素反应进行评估。如果结果为阳性，则研究将支持在胰腺移植相关情况下短期使用胰岛素。根据我们的经验，30%的患者在胰腺移植后血糖水平立即出现异常，这表明胰腺不能正常工作，可能会从胰岛素中获益。我计划研究支持胰腺移植后胰岛素治疗的临床和科学证据，并与一组领先的英国移植外科医生讨论研究结果。我们将决定是否在这些患者中进行胰岛素治疗试验，这将涉及患者咨询。如果证据和意见支持一项试验，那么我将在曼彻斯特设计一项可行性研究，并为试验申请研究资金。如果证据或意见不支持试验，那么我将领导撰写一份描述最佳实践的共识声明。这项研究有很大的潜力，以改善护理和长期结果的患者接受胰腺移植。