Reduced GLP-1 Secretion at 30 Minutes After a 75-g Oral Glucose Load Is Observed in Gestational Diabetes Mellitus: A Prospective Cohort Study

Glucagon-like peptide 1 (GLP-1) levels may be reduced in type 2 diabetes, but whether a similar impairment exists in gestational diabetes mellitus (GDM) has not been established. We studied this in a prospective cohort study of pregnant women ( n = 144) during oral glucose tolerance test (OGTT). GLP-1, glucose, and insulin were sampled at 30-min intervals during a 2-h 75-g OGTT, and indices of insulin secretion and sensitivity were calculated. In a nested case-control study, women with GDM ( n = 19) had 12% lower total GLP-1 secretion area under the curve (AUC) compared with control subjects matched for age, ethnicity, and gestational age ( n = 19), selected from within the lowest quartile of glucose 120 min values in our cohort. GDM had lower GLP-1 response in the first 30 min (19% lower GLP-1 30 min and 17% lower AUC 0-30 min ) after adjustment for possible confounders. Their glucose levels began to diverge at 30 min of the OGTT with increasing insulin levels, and by 120 min, their insulin levels were three times higher. In a secondary cohort of 57 women that included "high-normal" glucose 120 min values, low GLP-1 AUC 0-30 min was independently associated with lower indices of insulin secretion and sensitivity. In conclusion, we have observed that women with GDM have lower GLP-1 response at 30 min of an OGTT and hyperglycemia at 120 min despite significant hyperinsulinemia.