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

Abstract

Aims/hypothesis 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 firsttrimester prediction of GDM among obese and non-obese women compared with single markers. Methods A nested case-control study was performed on firsttrimester 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. Results 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, nonobese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. Conclusions/interpretation Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.

Molecular pathophysiology of diabetes mellitus during pregnancy with antenatal complications

“…The APOD concentration inversely depends on estrogens, i.e., 17β-estradiol, which is substantially increased during pregnancy 51 . Recently, APOD has already been considered as a predictive marker of GDM, but the data were ambiguous 52 . There were reports concerning the decrease of APOD in patients with GDM 52 and decreased concentration in cord blood samples of patients with uncomplicated pregnancy or excessive gestational weight gain 53 .…”

The role of mass spectrometry in studies of glycation processes and diabetes management

“…Also in this case the employment of this approach in a higher number of GDM cases would lead to a higher confidence of its validity. Ravnsborg et al (2016) undertook an exhaustive study based on a targeted mass spectrometric approach. First trimester serum samples from 199 GDM cases and 208 controls were considered and each population was divided into obese (BMI !27 kg/m 2 ) and non-obese (BMI <27 kg/m 2 ) groups.…”

Is the placental proteome impaired in well‐controlled gestational diabetes?

“…Ravnsborg et al undertook an exhaustive study based on a targeted mass spectrometric approach. A number of proteins were selected for a target analysis based on nano‐flow LC/MS.…”

“…Peptide ions detected by MALDI at m/z values of 1488.59, 3430.44, 443s76, 3158.72, and 4111.89 were indicated the most important variables in the model. 8 undertook an exhaustive study based on a targeted mass spectrometric approach. A number of proteins were selected for a target analysis based on nano-flow LC/MS.…”