Background: Pancreas transplantation is considered in patients with type 1 diabetes in whom usual medical management is not able to provide adequate glycaemic control or causes frequent severe episodes of hypoglycaemia. Benefits of transplantation in terms of correction of glycaemia (hyper- and hypoglycaemia) must be weighed carefully against risks associated with surgery and lifelong immunosuppression. Improved long-term graft survival would tip the risk-benefit balance in favour of transplantation. It is not clear what factors determine longterm metabolic graft function and there is currently no clinical measure to monitor graft function or identify dysfunction Methods: Glycaemic control, insulin secretion and insulin resistance was prospectively measured in patients awaiting pancreas and islet transplantation and in a cohort of pancreas transplant recipients (n=34) at 3 months after transplantation and yearly thereafter. Islet (n=2) transplant recipients were studied at 3 monthly intervals after transplantation. Results: Patients awaiting transplantation tend to be insulin sensitive. Pancreas transplantation normalises glycaemic control and restores insulin responses. Islet transplantation improves glycaemia to a lesser degree and partially restores insulin responses. Graft function appears to decline with time after transplantation with worsening glycaemia and gradual deterioration of insulin responses. A proportion of patients have clinical and sub-clinical abnormalities in glycaemic control, which may put them at risk of future decline in graft function. A fasting plasma glucose of > 5.5 mmol/L identifies patients who are at risk of future graft decline. In these patients a three-sample oral glucose tolerance test (OGTT) can confirm whether beta cell function is deteriorating. Conclusions: Although in the short term pancreas transplantation normalises glucose homeostasis, graft function declines over time. Fasting plasma glucose and OGTT are the easiest way of identifying graft dysfunction. Identification and further investigation of dysfunction may allow 'development of interventions to support graft function and prevent long-term decline.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:633150 |
| Date | January 2013 |
| Creators | Eckoldt, Stephanie Martina |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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