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

Rask, Eva; Olsson, Tommy; Soderberg, Stefan; Johnson, Owe; Seckl, Jonathan; Holst, Jens Juul; Ahren, Bo; Rask, E; Olsson, T; Söderberg, S; Johnson, O; Seckl, J; Holst, J J; Ahrén, B; Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)
September 2001
Diabetes Care;Sep2001, Vol. 24 Issue 9, p1640
Academic Journal
journal article
Objective: To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.Research Design and Methods: From a population-based study, 35 men were recruited, representing a wide spectrum of insulin sensitivity and body weight. Each subject underwent a hyperinsulinemic-euglycemic clamp to determine insulin sensitivity. A mixed meal was given, and plasma levels of gastric inhibitory polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), as well as insulin, glucagon, and glucose were measured.Results: Insulin resistance was associated with impaired GIP and GLP-1 responses to a mixed meal. The total area under the curve (AUC) of the GIP response 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 after food intake were significantly lower in the most insulin-resistant tertile compared with the most insulin-sensitive tertile. During the first hour, the AUC of GLP-1 correlated significantly with insulin sensitivity (r = 0.47, P < 0.01). Multiple linear regression analysis showed that insulin resistance, but not obesity, was an independent predictor of these decreased incretin 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. Decreased incretin responsiveness may be of importance for the development of impaired glucose tolerance.


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