Measuring postprandial pancreatic polypeptide (PP) plasma concentration is a sensitive method for autonomic nervous system assessment. Delayed gastric emptying (DGE) often does not correlate clearly with cardiac autonomic neuropathy (CAN). This study was conducted to evaluate whether decreased PP secretion (PPS) accompanies DGE and CAN in diabetes. Fourteen long-standing diabetics with DGE assessed by scintigraphy (group A), 14 well-matched diabetics with normal gastric emptying (NGE) (group B), and 12 healthy controls (group C) were the study subjects. CAN and postprandial PPS at 0, 30, and 60 min after test meal ingestion were examined in all the subjects, and the area under curve of PP secretion was calculated. There was no correlation between DGE and CAN (eight diabetics with CAN in A and six in B). Basal PP values were almost the same in all the patients (mean 77.27 +/- 11.0 pg/mL). The area under curve of PP secretion values (PPAUC) after test meal ingestion were significantly higher in B (211.84 +/- 36.13 pg/mL/h; p < 0.0001) and C (233.68 +/- 23.43 pg/mL/h; p < 0.00001) than in A (147.59 +/- 31.77 pg/mL/h). Diabetics with CAN had lower PPS expressed as PPAUC than those without CAN, which was independent of gastric emptying rate (152.31 +/- 37.18 versus 207.12 +/- 39.21 pg/mL/h; p < 0.001). There were no significant differences between test meal-stimulated PPAUC in diabetics without CAN (207.12 +/- 39.21 pg/mL/h) and controls (233.68 +/- 23.43 pg/mL/h), and this was also independent of gastric emptying rate. In patients with both DGE and CAN, the PPS was completely blunt (PPAUC 124.04 +/- 5.71 versus 233.68 +/- 23.43 pg/mL/h in controls; p < 0.001). The PPS in diabetics with CAN and NGE was significantly lower than in controls (PPAUC 190.0 +/- 37.45 versus 233.68 +/- 23.43 pg/mL/h; p < 0.01). In conclusion, the PPS in diabetics with CAN was decreased significantly and independently of DGE. The PP secretion was very low in diabetics with both CAN and DGE.