Abstract
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.