Metabolic characterization of long-term successful pancreas transplants in type I diabetes

Background: The encouraging results of the Diabetes Control and Complications Trial emphasize the need for improved methods of glycemic control to prevent the potentially devastating complications of Type I diabetes mellitus. However, current conventional approaches have failed to consistently achieve normal HbAlc levels and increase the risk of hypoglycemia. Pancreas transplantation is a consistently reliable method of achieving postoperative normal glucose levels, but no extensive assessment has been made of the long-term stability of its metabolic benefits. Methods: To ascertain long-term stability of metabolic function of pancreas transplants in Type I diabetic patients, we studied fasting glucose levels, glucose disposal after intravenous glucose challenge, HbAlc levels, and pancreatic islet beta and alpha cell responsiveness in a series of 96 successfully transplanted recipients. Patients were studied crosssectionally and, when possible, longitudinally for up to five years post-transplantation. Special emphasis was given to the longitudinal analysis to determine whether initial metabolic benefits maintain stability or undergo deterioration during the first five postoperative years. Results: Pancreas transplantation was accompanied by normal or nearly normal fasting plasma glucose levels, intravenous glucose disappearance rates, and HbAlc levels. Beta cell function assessed by acute insulin responses and acute C-peptide responses to intravenous glucose injections revealed no deterioration in the magnitude of these responses. Analysis of acute insulin and C-peptide responses to intravenous arginine provided similar results. Alpha cell function, assessed by measuring acute glucagon responses to intravenous arginine, were significantly (p > .001) greater than preoperative responses and remained stable over the ensuing five-year period. In grafts that maintained function, none of these metabolic measures showed deterioration during the five-year postoperative period. Conclusions: Successful pancreas transplantation provides pancreatic islet function that results in normal or near normal glycemic control for up to five years postoperatively in Type I diabetic recipients receiving no exogenous insulin or oral hypoglycemic agent therapy.