Effects of pancreas transplantation on postprandial glucose metabolism

Background. Because a pancreas allograft is placed in the pelvis, pancreas transplantation abolishes the normal gradient between portal-vein and peripheral-vein insulin concentrations and causes systemic hyperinsulinemia. Whether pancreas transplantation restores carbohydrate metabolism to normal is not known. Methods. We studied seven patients with insulin-dependent diabetes mellitus after pancreas-kidney transplantation, seven nondiabetic patients after kidney transplantation (to control for immunosuppression), and eight normal subjects. Measurements were made after an overnight fast and after ingestion of a mixed meal. Results. Although plasma glucose concentrations did not differ in the two transplant groups, plasma insulin concentrations were significantly higher in the diabetic pancreas-kidney recipients than in the nondiabetic kidney recipients, both before the meal (mean ±SE, 102±15 vs. 53±6 pmol per liter; P<0.05) and afterward (123±22 vs. 61±6 nmol per liter per six hours; P<0.05). Plasma C-peptide concentrations were the same in both groups, indicating that hyperinsulinemia was due to decreased insulin clearance rather than increased insulin secretion. Despite drainage of the venous effluent from the transplanted pancreas into the systemic circulation, the values for splanchnic clearance of ingested glucose, suppression of hepatic glucose release, incorporation of carbon dioxide into glucose, stimulation of glucose oxidation, glucose uptake, and forearm glucose clearance were all similar in the transplant groups and differed minimally from the values in the normal group. The similar rates of glucose uptake in the presence of higher systemic insulin concentrations indicated that the extrahepatic tissues of the diabetic pancreas-kidney recipients were insulin-resistant. Conclusions. Despite systemic delivery of insulin, pancreas-kidney transplantation in patients with diabetes results in carbohydrate metabolism similar to that in nondiabetic subjects receiving the same immunosuppressive agents after kidney transplantation.