title: Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men.
abstract: OBJECTIVE
  To investigate whether features of the insulin resistance syndrome are associated with altered incretin responses to food intake.
  
  
  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.
authors.affiliation: Department of Public Health and Clinical Medicine, Umeå University Hospital, 901 85 Umeå, Sweden. eva.rask@medicin.umu.se
authors.forename: E
authors.initials: E
authors.lastname: Rask
authors.forename: T
authors.initials: T
authors.lastname: Olsson
authors.forename: S
authors.initials: S
authors.lastname: Söderberg
authors.forename: O
authors.initials: O
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Seckl
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D001835:Body Weight; D004435:Eating; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005768:Gastrointestinal Hormones / Q000097:blood* / Q000378:metabolism; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood* / Q000378:metabolism; D019518:Postprandial Period / Q000502:physiology*; D011498:Protein Precursors / Q000097:blood; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon