Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men
- Eva Rask, MD1,
- Tommy Olsson, MD, PHD1,
- Stefan Söderberg, MD, PHD1,
- Owe Johnson, MD, PHD1,
- Jonathan Seckl, MD, PHD2,
- Jens Juul Holst, MD, PHD3 and
- Bo Ahrén, MD, PHD4
- 1Department of Public Health and Clinical Medicine, Umeå University Hospital, Umeå, Sweden
- 2Molecular Endocrinology Laboratory, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, U.K.
- 3Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
- 4Department of Medicine, Lund University, Lund, Sweden
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.
- ANOVA, analysis of variance
- AUC, area under the curve
- CV, coefficients of variation
- DPP-IV, dipeptidyl-peptidase IV
- HOMA, homeostasis model assessment
- GIP, gastric inhibitory polypeptide
- GLP-1, glucagon-like peptide 1
- IGT, impaired glucose tolerance
- MONICA, Monitoring of Trends and Determinants in Cardiovascular Disease
- NEFA, nonesterified fatty acid
- RIA, radioimmunoassay
Address correspondence and reprint requests to Eva Rask, Department of Public Health and Clinical Medicine, Umeå University Hospital, 901 85 Umeå, Sweden. E-mail:.
Received for publication 1 March 2001 and accepted in revised form 6 June 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.