Glucose Counterregulation in Patients After Pancreatectomy: Comparison With Other Clinical Forms of Diabetes

Abstract

Glucose and counterregulatory hormone responses to a high-dose (1.7 mU/kg/min) insulin infusion were studied in 6 patients who had undergone total pancreatectomy, and the results were compared with those of normal controls and patients with other clinical forms of diabetes. The maximum increase in the plasma glucagon concentration during hypoglycemia in the pancreatectomized patients (5 ± 5.6 pg/ml) was less than in normals (121 ± 22 pg/ml). Type I diabetic subjects (28 ± 14 pg/ml), and insulin-treated diabetic subjects of recent onset (36 ± 12 pg/ml) also had reduced responses, while responses were normal in type II diabetic subjects (102 ± 26 pg/ml). The epinephrine response to the hypoglycemie stimulus was reduced after pancreatectomy (278 ± 81 pg/ml) and in type I diabetic subjects (628 ± 244 pg/ml), but was not different from control (858 ±126 pg/ml) in type II and recent-onset diabetic patients. There was considerable overlap in counterregulatory hormone responses in individual patients with and without autonomie neuropathy and with normal or undetectable fasting C-peptide concentrations. While the control subjects all experienced symptoms of hypoglycemia within a narrow range of plasma glucose concentrations (35–46 mg/dl), five of the diabetic subjects experienced symptoms of hypoglycemia at plasma glucose levels of > 55 mg/dl, and five had no subjective awareness of hypoglycemia despite plasma glucose levels < 30 mg/dl. Thus, (1) after pancreatectomy both glucagon and epinephrine responses are reduced, resulting in markedly impaired glucose recovery from insulin-induced hypoglycemia; (2) glucagon responses may be abnormal in insulin-treated diabetic subjects within the first year of diagnosis, despite relatively normal fasting C-peptide concentrations and no clinical evidence of autonomie neuropathy; and (3) glucagon and epinephrine responses are normal in type II diabetic subjects even if the disease is of prolonged duration and clinical evidence of autonomie neuropathy is present.