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

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.

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 cross-sectionally 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.

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.

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.