Prediction of the long-term metabolic success of the pancreatic graft function

Background. Strategies to prevent the return to the diabetic state for graf t loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether d aily glucose, insulin, and c-peptide profiles and studies of insulin sensit ivity and secretion after transplantation predict pancreatic graft failure. Methods, Fifty-three subjects with type 1 diabetes with end-stage renal fai lure who received a combined pancreas and kidney transplant underwent the f ollowing procedures 1 year after transplantation: I-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n =51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin sec retion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitiv ity (M value, n=14), The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state. Results, Survival analysis showed that plasma glucose in the profiles and i nsulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL , corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cuto ff value of insulin delta peak <32 <mu>U/ml in the IVGTT predicted the retu rn to the diabetic state within 4 years from transplantation with a 75% spe cificity and a 75% sensitivity. In contrast, the M value in the clamp was d evoid of predictive value. Conclusions. This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabe tic state. The risk is related to defects in insulin secretion and not to i nsulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early deter minants of graft failure.