TY - JOUR
T1 - Defects in GLP-1 response to an oral challenge do not play a significant role in the pathogenesis of prediabetes
AU - Smushkin, Galina
AU - Sathananthan, Airani
AU - Man, Chiara Dalla
AU - Zinsmeister, Alan R.
AU - Camilleri, Michael
AU - Cobelli, Claudio
AU - Rizza, Robert A.
AU - Vella, Adrian
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84856784864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856784864&partnerID=8YFLogxK
U2 - 10.1210/jc.2011-2561
DO - 10.1210/jc.2011-2561
M3 - Article
C2 - 22090278
AN - SCOPUS:84856784864
SN - 0021-972X
VL - 97
SP - 589
EP - 598
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -