Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients.
To elucidate the causes of the diminished incretin effect in type 2 diabetes mellitus we investigated the secretion of the incretin hormones, glucagon-like peptide-1 and glucose- dependent insulinotropic polypeptide and measured nonesterified fatty acids, and plasma concentrations of insulin, C peptide, pancreatic polypeptide, and glucose during a 4-h mixed meal test in 54 heterogeneous type 2 diabetic patients, 33 matched control subjects with normal glucose tolerance, and 15 unmatched subjects with impaired glucose tolerance. The glucagon-like peptide-1 response in terms of area under the curve from 0-240 min after the start of the meal was significantly decreased in the patients (2482 +/- 145 compared with 3101 +/- 198 pmol/liter.240 min; P = 0.024). In addition, the area under the curve for glucose-dependent insulinotropic polypeptide was slightly decreased. In a multiple regression analysis, a model with diabetes, body mass index, male sex, insulin area under the curve (negative influence), glucose-dependent insulinotropic polypeptide area under the curve (negative influence), and glucagon area under the curve (positive influence) explained 42% of the variability of the glucagon-like peptide-1 response. The impaired glucose tolerance subjects were hyperinsulinemic and generally showed the same abnormalities as the diabetic patients, but to a lesser degree. We conclude that the meal-related glucagon-like peptide-1 response in type 2 diabetes is decreased, which may contribute to the decreased incretin effect in type 2 diabetes.
Toft-Nielsen
M B
MB
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, DK-2650 Hvidovre, Denmark.
Damholt
M B
MB
Madsbad
S
S
Hilsted
L M
LM
Hughes
T E
TE
Michelsen
B K
BK
Holst
J J
JJ
D000704:Analysis of Variance; D001323:Autoantibodies / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D018149:Glucose Intolerance / Q000097:blood* / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010191:Pancreatic Polypeptide / Q000097:blood; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism*; D012016:Reference Values
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D007328:Insulin; D010191:Pancreatic Polypeptide; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; C096322:ICA512 autoantibody