Is pancreatic polypeptide response to food ingestion a reliable index of vagal function in type 1 diabetes?

Objective. The diagnosis of autonomic neuropathy in diabetic patients is based on cardiovascular reflex tests. Since cardiac function may be affected by arteriosclerosis and cardiomyopathy in type 1 diabetes mellitus, alternative tests reflecting vagal nerve function, in other organ systems, are needed. In this study the pancreatic polypeptide (PP) response to a mixed meal was evaluated in healthy subjects and in recently diagnosed type 1 diabetic patients. Material and methods. The PP response was studied at different levels of the vagally mediated reflex arch by application of different stimuli: meal ingestion, i.v. edrophonium (a cholinesterase inhibitor) injection and arginine infusion. Results. Meal ingestion (stimulation of cerebral/vagal level) resulted in a significant and similar PP response in the two groups; i.v. edrophonium injection (stimulating at the second neuron level) resulted in a smaller increase in PP concentrations in the type 1 diabetic patients as compared with the healthy subjects, whereas direct PP-cell stimulation by arginine infusion resulted in similar increments in PP concentrations in the two groups. Thus, in recently diagnosed type 1 diabetic patients with no known manifestations of diabetic neuropathy, the cholinergic second neuron function of the vagal arch to the pancreas is impaired, whereas intrinsic PP-cell function is unaffected. Conclusions. This abnormality in cholinergic second neuron function of the vagal reflex arch and the fact that three of the healthy subjects had no increase in PP concentrations at all during the meal test indicates that PP response to a mixed meal is unsuitable for the diagnosis of autonomic neuropathy in type 1 diabetes. The nature of the defect in the second neuron of the vagal innervation of the pancreas in type 1 diabetes remains to be elucidated.