Association of GLP-1 secretion with parameters of glycemic control in women after gestational diabetes mellitus.

Introduction: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes, while the exact mechanisms underlying its pathophysiology are still unclear. We investigated the association of glucagon-like peptide-1 (GLP-1) response to oral glucose with parameters of glycemic control in women with previous GDM in the prospective PPSDiab (Prediction, Prevention, and Subclassification of Type 2 Diabetes) study.

Research design and methods: Glucose metabolism parameters and GLP-1 secretion were analyzed during oral glucose tolerance test (OGTT) in women with previous GDM (n=129) and women with a history of normal glucose tolerance (n=67) during pregnancy (controls). First- and second-phase insulin and GLP-1 secretion in relation to plasma glucose (PG) levels were assessed, and development of pre-diabetes was analyzed after 5-year follow-up among women with previous GDM and a normal glycemic state at baseline (n=58).

Results: The area under the curve (AUC during the OGTT 0-120 min) of PG and insulin but not GLP-1 differed significantly between post-GDM women and controls. However, women with previous GDM had a significantly decreased GLP-1 response in relation to PG and plasma insulin during the second phase of the OGTT. After a follow-up of 5 years, 19.0% post-GDM women with a normal glycemic state at the baseline visit developed abnormal glucose metabolism. The total, first- and second-phase AUC GLP-1/PG and GLP-1/insulin ratios were not associated with development of abnormal glucose tolerance.

Conclusions: Women with previous GDM showed a reduced GLP-1 response in relation to PG and insulin concentrations indicating early abnormalities in glucose metabolism. However, the altered GLP-1 response to oral glucose did not predict progression to pre-diabetes and type 2 diabetes in the first 5 years after GDM.