After successful pancreas transplantation, recipients with type I diabetes mellitus achieve a return to normal fasting plasma glucose levels, normal oral glucose tolerance tests, and normal levels of HbA,C (1-7). However, whether recipients undergo alterations in counterregulatory hormonal responses to glycopenia, or improvement in counterregulation of hypoglycemia, has not been determined. These are important considerations because type I diabetic patients commonly have defective glucagon and epinephrine responses to hypoglycemia and, consequently, deranged counterregulation of hypoglycemia with its attendant risks (8-13). Therefore, presence or absence of improvement in these responses are highly relevant factors in the evaluation of the overall benefits of pancreas transplantation. Moreover, since the transplanted pancreas is denervated and since islet alpha cell and pancreatic polypeptide cell function is neurally modulated, investigation of pancreas recipients offers a unique opportunity to assess regulation ofglucagon and pancreatic polypeptide secretion from the pancreas in humans in the setting of absent central nervous system input into the islet.To evaluate hormonal counterregulation of hypoglycemia in patients with type I diabetes mellitus who have received successful pancreas allografts, we have examined glucose, glucagon, pancreatic polypeptide, and catecholamine responses during insulin-induced hypoglycemia. We have also assessed glucagon and pancreatic polypeptide responsivity to direct stimulators of alpha and pancreatic polypeptide cells (arginine and secretin, respectively) to ascertain whether possible alterations in secretory responses in pancreas recipients are specific for hypoglycemic signaling or more general in nature. In this study, the responses of pancreas recipients were compared with responses of patients with similar durations of type I diabetes mellitus, who had not received pancreas transplantation, and to nondiabetic control subjects.
MethodsSubjects. 38 type I diabetic recipients of pancreas allografts with iliac vessel anastomoses and with intact native pancreases who had been transplanted between 3 and 60 mo previously were studied (Table I). All recipients were normoglycemic, had normal hemoglobin A,C levels and mildly elevated serum creatinine levels, and none were receiving exogenous insulin or other medication for diabetes. Immunosuppression was achieved with the triple-drug regimen of azathioprine, cyclosporine, and prednisone (14). 54 patients with type I diabetes and with similar age, sex distribution, body-mass index, serum creatinine levels, and duration ofdiabetes, as well as 26 normal volunteers of similar age, sex distribution, and body-mass index, were studied to obtain control data. All subjects were admitted to the University