Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men

OBJECTIVE - To investigate whether features of the insulin resistance syndr ome are associated with altered incretin responses to food intake. RESEARCH DESIGN AND METHODS- From a population-based study, 35 men were rec ruited, representing a wide spectrum of insulin sensitivity and body weight . Each subject underwent a hyperinsulinemic-euglycemic clamp to determine i nsulin sensitivity. A mixed meal was given, and plasma levels of gastric in hibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured. RESULTS- insulin resistance was associated vith impaired GIP and GLP-1 resp onses to a mixed meal. The total area under the curve (AUC) of the GIP resp onse after the mixed meal was associated with insulin sensitivity (r = 0.54 . P < 0.01). There was a significant difference between the highest and the lowest tertile of insulin sensitivity (P < 0.05). GLP-1 levels 15 min afte r food intake were significantly lower in the most insulin-resistant tertil e compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.4 7, P < 0.01). Multiple linear regression analysis showed that insulin resis tance, but not obesity, was an independent predictor of these decreased inc retin responses. CONCLUSIONS - in insulin resistance, the GIP and GLP-1 responses to a mixed meal are impaired and are related to the degree of insulin resistance. Dec reased incretin responsiveness may be of importance for the development of impaired glucose tolerance.