Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139±18 vs 72±7 pg/ml;P<0.01). Integrated postprandial CCK response was increased in DM patients (208±27 vs 110±14 pmol/liter/2 hr;P<0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273±5241 vs 13,418±3299 pg/ml/2 hr;P<0.001) but not in those with AN (8887±3461 pg/ml/2 hr). Moreover, PP response was closely (P<0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r=0.78;P<0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system. It is suggested that the correlation between postprandial hormonal responses in healthy subjects is due to the potency of CCK as PP releasing agent and that this interaction does not work in diabetic patients.