Background: The aim of this study was to determine the effect of diabetic autonomic neuropathy (AN) on the incretin effect ill patients with type 2 diabetes mellitus (DM2). Material/Methods: Forty patients with DM2 (20 with and 20 without AN) and 10 healthy controls were studied. The subjects underwent, an oral glucose tolerance test (OGTT) and 7-14 days later all intravenous infusion of 25 g glucose. Blood samples were drawn for glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) determination during the tests. The incretin effect was calculated from (lie total integrated amount of insulin or G-peptide during OGFTT (A) and intravenous glucose infusion (B) according to the formula (A-B)/Ax100. Results: 'Total insulin and C-peptide responses during OGTT were significantly higher than those after IV glucose infusion in the group of normal subjects, but not in the groups of diabetic patients. After oral glucose load, GIP levels presented a significant increase ill normal subjects and patients without AN, whereas GLP-1 levels increased only ill normal subjects. Calculated either with the insulin or C-peptide responses, the incretin effect presented no significant difference between the two diabetic groups. However using insulin responses, only the patients with AN had significantly lower incretin effect than controls, whereas when using C-peptide responses, both diabetic groups did. Conclusions: The incretin effect was impaired in both groups of diabetic patients. Antonomic neuropathy may further impair the incretin effect ill DM2 through interference with GIP secretion or hepatic insulin extraction..