Endocrine Abstracts

Background: Glucagon-like peptide-1 (GLP-1) concentrations are reduced by 20–50% in type 2 diabetes but studies in women with gestational diabetes mellitus (GDM) are inconclusive. Our aim was to study the GLP-1 profile during a glucose tolerance test (GTT) at GDM diagnosis and its relationship with insulin levels.

Methods: A prospective study of selectively screened women was conducted. Plasma GLP-1, insulin and glucose were measured at 30-minute intervals during a 2-hour 75 g GTT. GDM was diagnosed according to UK NICE guidelines (glucose_0min ≥5.6 mmol/l or glucose_120min ≥7.8 mmol/l) and the parameters were additionally considered as continuous variables in linear regression models.

Results: Hundred and forty-five women were recruited and 19 developed GDM (glucose_120min range 7.8–12.1 mmol/l). 19 controls, with the lowest glucose_120min values in our cohort (range 4.0–4.5 mmol/l), were identified. GLP_30min concentrations were significantly lower in GDM women than controls after adjusting for covariates (Table 1). GLP-1 total area under the curve (AUC) was reduced by 13% in GDM (adjusted P<0.05) but mean GLP-1 and incremental AUC were similar. Serum insulin levels from 0 to 90 min were similar in the two groups but GDM women had over two times higher insulin_120min (481 vs 211 pmol/l, adjusted P=0.001). GLP_0min and GLP_30min were negatively correlated with insulin_120min. GLP_30min also independently predicted insulin sensitivity index, measured by Stumvoll formula (β-coefficient=0.152, P=0.038), thus contributing to post-prandial hyperglycaemia. There were no associations between GLP-1 levels at other time-points and any glucose or insulin parameters.

Conclusion: Total and early (GLP_30min) GLP-1 response are reduced by 13–20% in GDM women respectively. Lower GLP_30min levels are independently linked to lower insulin sensitivity, thus suggesting a novel mechanism to explain the pathogenesis of GDM.