First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

Tina Ravnsborg, Lise Lotte T. Andersen, Natacha D. Trabjerg, Lars M. Rasmussen, Dorte M. Jensen, Martin Overgaard

Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve first-trimester prediction of GDM among obese and non-obese women compared with single markers. A nested case-control study was performed on first-trimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI ≥27 kg/m(2)) and a non-obese group (BMI <27 kg/m(2)). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay. After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, non-obese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.