Glucose-dependent insulin-releasing peptide in noninsulin-dependent maturity-onset diabetes: effects of autonomic neuropathy.

Glucose-dependent insulin-releasing peptide or gastric inhibitory polypeptide (GIP) is released into the circulation after ingestion of a mixed meal and is thought to enhance glucose-induced insulin release. We investigated basal and meal-stimulated GIP secretion in noninsulin-dependent maturity-onset diabetics (MODs). Twelve MODs and 12 healthy normal subjects were studied. Mean (+/- SE) basal plasma GIP concentrations were similar in MODs (297 +/- 34.5 pg/ml) and healthy subjects (305 +/- 29.7 pg/ml). Overnight insulin infusion normalized basal glucose levels in the MODs and induced a slight but insignificant rise in plasma GIP levels in MODs to 362 +/- 40.9 pg/ml; overnight gastric aspiration caused a further slight rise in basal GIP concentration to 392 +/- 56.6 pg/ml. The GIP responses to a mixed meal were significantly impaired at 90-240 min in MODs. The MODs were divided into 2 groups, each with 6 subjects: 1 group with autonomic neuropathy (AN) and the other without. The GIP responses in MODs without AN were similar to those in healthy subjects, but were significantly reduced in MODs with AN at all times after the meal. We suggest that the release of GIP after a meal is dependent upon the integrity of the autonomic nervous system; the mechanism may be related to the loss of autonomic control of gastric emptying or dependence of GIP secretion on autonomic modulation.