Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients

J Clin Endocrinol Metab. 2001 Aug;86(8):3717-23. doi: 10.1210/jcem.86.8.7750.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Autoantibodies / blood
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Fasting
  • Fatty Acids, Nonesterified / blood
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Glucagon / blood
  • Glucagon / metabolism*
  • Glucagon-Like Peptide 1
  • Glucose Intolerance / blood*
  • Glucose Intolerance / physiopathology
  • Glutamate Decarboxylase / immunology
  • Glycated Hemoglobin A / analysis
  • Humans
  • Insulin / blood
  • Male
  • Middle Aged
  • Pancreatic Polypeptide / blood
  • Peptide Fragments / blood
  • Peptide Fragments / metabolism*
  • Peptides / blood
  • Peptides / metabolism*
  • Protein Precursors / blood
  • Protein Precursors / metabolism*
  • Reference Values

Substances

  • Autoantibodies
  • Blood Glucose
  • C-Peptide
  • Fatty Acids, Nonesterified
  • Glycated Hemoglobin A
  • ICA512 autoantibody
  • Insulin
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Gastric Inhibitory Polypeptide
  • Pancreatic Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glutamate Decarboxylase