Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men

• DOI: 10.2337/diacare.24.9.1640
• Publication Date: 2007-03-05T22:51:27Z
• Authors: Eva Rask; Tommy Olsson; Stefan Söderberg; Owe Johnson; Jonathan Seckl; Jens Juul Holst; Bo Ahrén
• Keywords: Adult; Blood Glucose; Male; 2. Zero hunger; Body Weight; Glucagon-Like Peptides; Blood Pressure; Gastric Inhibitory Polypeptide; Middle Aged; Glucagon; Postprandial Period; Peptide Fragments; Gastrointestinal Hormones; Eating; 03 medical and health sciences; 0302 clinical medicine; Glucagon-Like Peptide 1; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Protein Precursors; Biomarkers

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.