Impaired circulating glucagon-like peptide-1 response to oral glucose in women with previous gestational diabetes.
OBJECTIVE
Women with previous gestational diabetes (pGDM) are at risk of developing Type 2 diabetes. Glucagon-like peptide-1 (GLP-1) potentiates the insulin response to oral glucose, and its secretion is diminished in Type 2 diabetes. The aim of the study was to see if decreased GLP-1 secretion might be an early abnormality in the progression to Type 2 diabetes and would therefore be diminished in women with pGDM.


METHODS
Eleven women with pGDM and previously documented normal glucose tolerance and 11 control women underwent a 75 g oral glucose tolerance test (OGTT). Circulating plasma glucose, insulin, nonesterified fatty acids (NEFA) and GLP-1 concentrations were sampled.


RESULTS
One of the women with pGDM had impaired glucose tolerance and was excluded from the study. All other women had normal glucose tolerance. The women with pGDM had higher fasting glucose concentrations than controls (5.1; 4.9-5.3 vs. 4.8; 4.4-5.1 mmol/l, median; interquartile range, P = 0.04) and greater circulating glucose area under the curve (AUC) following the oral glucose load (930; 818-1015 vs. 668; 584-737 min x mmol/l, P = 0.0007). Fasting insulin concentrations and total insulin AUC were similar. The initial (0-30 min) insulin response was decreased in the pGDM women (AUC 3981; 2783-4795 vs. 6167; 5009-8145 min x pmol/l, P = 0.05). The initial (0-30 min) GLP-1 response was reduced in the pGDM women (AUC 816; 663-984 vs. 1163; 872-2024 min x pmol/l, P = 0.02).


CONCLUSIONS
A reduced initial GLP-1 response to oral glucose may therefore be an early abnormality in the progression to Type 2 diabetes.
Forbes
Shareen
S
Endocrinology and Metabolic Medicine, Faculty of Medicine, Imperial College London, London, UK. shareen.forbes@imperial.ac.uk
Moonan
May
M
Robinson
Stephen
S
Anyaoku
Victor
V
Patterson
Michael
M
Murphy
Kevin G
KG
Ghatei
Mohammed A
MA
Bloom
Stephen R
SR
Johnston
Desmond G
DG
D000328:Adult; D019540:Area Under Curve; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood*; D005260:Female; D005934:Glucagon / Q000032:analysis*; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D010446:Peptide Fragments / Q000032:analysis*; D011247:Pregnancy; D011498:Protein Precursors / Q000032:analysis*; D012636:Secretory Rate / Q000187:drug effects
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose