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

Galina Smushkin, Airani Sathananthan, Chiara Dalla Man, Alan R. Zinsmeister, Michael Camilleri, Claudio Cobelli, Robert A. Rizza, Adrian Vella

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Context: There has beenmuchspeculation 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:Weevaluated 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 (rs=-0.16 and P=0.14, and rs=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.

Original languageEnglish (US)
Pages (from-to)589-598
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number2
StatePublished - Feb 2012

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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