| Summary: | Background New Onset Diabetes After Transplantation (NODAT) is an important complication of renal transplantation associated with decreased graft and patient survival. This study aimed to validate established physiological measures of glucose homeostasis in the renal transplant population and use these techniques to establish the range of glucose handling in patients pre-transplant and the impact of transplantation on glucose handling. The main impact of NODAT is an increase in cardiovascular risk. Cardiovascular assessments were therefore performed in all patients in parallel with assessments of glucose homeostasis. Patients and Methods The study involved two distinct cohorts of patients: Patients identified retrospectively by an electronic database and a prospective cohort of patients on the live kidney donor waiting list whom were in the final stages of work-up for listing for a date for surgery. The retrospective cohort were analysed to establish epidemiological factors that predict NODAT and determine the natural history of NODAT in patients treated at our unit. A sub-group of this cohort was those who appeared to have recovered from NODAT on the basis of measurement of fasting plasma glucose, random plasma glucose or HbA1c. These patients underwent an oral glucose tolerance test (OGTT) to verify their diabetes status and perform the Homeostasis Model Assessment (HOMA) to estimate their beta cell function (%8) and insulin sensitivity (%S). The prospective cohort underwent an OGTT before transplant (n=18). 12 of the cohort also underwent a euglycaemic hyperinsulinaemic clamp study and 5 an arginine intravenous glucose tolerance test. Repeat testing was performed at 3 months. Finally cardiovascular assessment was performed in all patients by measurement of augmentation index and mean arterial blood pressure. Results The retrospective analysis of 306 consecutive renal transplants over 3 years demonstrated age at time of transplant and family history of diabetes to be predictors of development of NODA T. Also 10 of 12 individuals thought to have resolved from NODAT as judged by random and fasting glucose measurement and off hypoglycaemic and insulin treatment were shown to still have abnormal glucose handling, 8 were still diabetic as judged by a OGTT. Within the LKD cohort (n=18) the pre-transplant OGTT demonstrated 4 participants to have IGT and 2 participants to have diabetes. Glucose disposal rate (GDR) fell Significantly from pre to post transplant. Discussion This study has shown that insulin resistance is increased at three months post live donor kidney transplant. There was a trend also for pancreatic beta cell function to decline. Cardiovascular risk factors were shown to have not changed by three months. Our long-term objective is to create an algorithm that will enable clinicians to define the overall individual risk of developing NODAT. This will result in more rigorous surveillance of the individual and, with development of novel regimens, tailoring of post-transplant immunosuppression to ensure optimum protection from rejection and avoid the significant cardiovascular morbidity and mortality associated with developing diabetes. Resolution of NODAT should be based solely on an OGTT and long term surveillance offered as part of the graft follow-up. ii.
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