The impact of diabetic autonomic neuropathy on the incretin effect.
BACKGROUND
The aim of this study was to determine the effect of diabetic autonomic neuropathy (AN) on the incretin effect in patients with type 2 diabetes mellitus (DM2).


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 an 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 the total integrated amount of insulin or C-peptide during OGTT (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 the oral glucose load, GIP levels presented a significant increase in normal subjects and patients without AN, whereas GLP-1 levels increased only in 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. Autonomic neuropathy may further impair the incretin effect in DM2 through interference with GIP secretion or hepatic insulin extraction.
Kazakos
Kiriakos A
KA
1st Department of Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Sarafidis
Pantelis A
PA
Yovos
John G
JG
D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006262:Health; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male
D002096:C-Peptide; D054795:Incretins; D007328:Insulin