Impaired incretin response after a mixed meal is associated with insulin resistance in nondiabetic men.
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.
Rask
E
E
Department of Public Health and Clinical Medicine, Umeå University Hospital, 901 85 Umeå, Sweden. eva.rask@medicin.umu.se
Olsson
T
T
Söderberg
S
S
Johnson
O
O
Seckl
J
J
Holst
J J
JJ
Ahrén
B
B
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
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