Subnormal Pancreatic Polypeptide and Epinephrine Responses to Insulin-Induced Hypoglycemia Identify Patients with Insulin-Dependent Diabetes Mellitus Predisposed to Develop Overt Autonomic Neuropathy

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Abstract
Sixteen patients with insulin-dependent diabetes mellitus with no current evidence of autonomic dysfunction underwent an insulin tolerance test during which plasma pancreatic polypeptide and epinephrine responses were determined. Compared to 11-age- and weight-matched nondiabetic volunteers, 9 diabetic subjects had subnromal plasma pancreatic polypeptide responses (n = 6) or plasma epinephrine responses (n = 8). When autonomic function was reassessed 2 to 3 years later by standard cardiovascular reflex tests and clinical examination, 8 of 9 diabetic subjects with subnormal hormonal responses to hypoglycemia developed either abnormal cardiovascular reflexes (6 of 9) or overt symptoms consistent with diabetic autonomic neuropathy (6 of 9), whereas none of the subjects with previously normal plasma pancreatic polypeptide and epinephrine responses and epinephrine responses did (P < 0.01). Diminished pancreatic polypeptide and epinephrine responses to hypoglycemia can predict the development of overt autonomic neuropathy in patients with insulin-dependent diabetes mellitus; identification of patients with a predilection to develop autonomic neuropathy may permit earlier treatment.