Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes

J Clin Endocrinol Metab. 2012 Feb;97(2):589-98. doi: 10.1210/jc.2011-2561. Epub 2011 Nov 16.


Context: There has been much speculation as to whether defects in glucagon-like peptide-1 (GLP-1) secretion play a role in the pathogenesis of type 2 diabetes and the progression from normal glucose tolerance to prediabetes and diabetes.

Objective: Our objective was to determine whether fasting and postchallenge concentrations of active and total GLP-1 decrease as glucose tolerance and insulin secretion worsen across the spectrum of prediabetes.

Design: This was a cross-sectional study.

Setting: The study was performed in the clinical research unit of an academic medical center.

Participants: Participants included 165 subjects with a fasting glucose below 7.0 mmol/liter and not taking medications known to affect gastrointestinal motility or glucose metabolism.

Intervention: Intervention included a 2-h, 75-g oral glucose tolerance test with insulin, C-peptide, glucagon, and GLP-1 measurements at seven time points.

Main outcome measure: We evaluated the association of integrated, incremental active, and total GLP-1 concentrations with integrated, incremental glucose response to 75 g oral glucose.

Results: After accounting for covariates, there was no evidence of a relationship of incremental glucose concentrations after oral glucose tolerance test with active and total GLP-1 (r(s) = -0.16 and P = 0.14, and r(s) = 0.00 and P > 0.9, respectively). There also was no association of GLP-1 concentrations with insulin secretion and action.

Conclusions: The lack of association of GLP-1 concentrations with glucose tolerance status and with insulin secretion and action in a cohort encompassing the full spectrum of prediabetes strongly argues against a significant contribution of defects in GLP-1 secretion to the pathogenesis of prediabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • C-Peptide / analysis
  • C-Peptide / blood
  • Cross-Sectional Studies
  • Female
  • Glucagon-Like Peptide 1 / analysis
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / physiology
  • Glucose / administration & dosage*
  • Glucose Tolerance Test / methods
  • Humans
  • Insulin / analysis
  • Insulin / blood
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Prediabetic State / blood
  • Prediabetic State / etiology*
  • Prediabetic State / metabolism


  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucagon-Like Peptide 1
  • Glucose