title: Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a cross-sectional study.
  
  
  METHODS
  The study was performed in the clinical research unit of an academic medical center.
  
  
  METHODS
  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.
  
  
  METHODS
  Intervention included a 2-h, 75-g oral glucose tolerance test with insulin, C-peptide, glucagon, and GLP-1 measurements at seven time points.
  
  
  METHODS
  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.
authors.affiliation: Division of Endocrinology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Smushkin
authors.forename: Airani
authors.initials: A
authors.lastname: Sathananthan
authors.forename: Chiara Dalla
authors.initials: CD
authors.lastname: Man
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D002096:C-Peptide / Q000032:analysis / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000032:analysis / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage*; D005951:Glucose Tolerance Test / Q000379:methods; D006801:Humans; D007328:Insulin / Q000032:analysis / Q000097:blood; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011236:Prediabetic State / Q000097:blood / Q000209:etiology* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005947:Glucose
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