Metabolomic Identification of a Novel, Externally Validated Predictive Test for Gestational Diabetes Mellitus

Context Undiagnosed gestational diabetes mellitus (GDM) is a major preventable cause of stillbirth. In the United Kingdom, women are selected for diagnostic testing for GDM based on risk factors, including body mass index (BMI) > 30 kg/m(2). Objective To improve the prediction of GDM using metabolomics. Methods We performed metabolomics on maternal serum from the Pregnancy Outcome Prediction (POP) study at 12 and 20 weeks of gestational age (wkGA; 185 GDM cases and 314 noncases). Predictive metabolites were internally validated using the 28 wkGA POP study serum sample and externally validated using 24- to 28-wkGA fasting plasma from the Born in Bradford (BiB) cohort (349 GDM cases and 2347 noncases). The predictive ability of a model including the metabolites was compared with BMI > 30 kg/m(2) in the POP study. Results Forty-seven predictive metabolites were identified using the 12- and 20-wkGA samples. At 28 wkGA, 4 of these [mannose, 4-hydroxyglutamate, 1,5-anhydroglucitol, and lactosyl-N-palmitoyl-sphingosine (d18:1/16:0)] independently increased the bootstrapped area under the receiver operating characteristic curve (AUC) by >0.01. All 4 were externally validated in the BiB samples (P = 2.6 x 10(-12), 2.2 x 10(-13), 6.9 x 10(-28), and 2.6 x 10(-17), respectively). In the POP study, BMI > 30 kg/m(2) had a sensitivity of 28.7% (95% CI 22.3-36.0%) and a specificity of 85.4% whereas at the same level of specificity, a predictive model using age, BMI, and the 4 metabolites had a sensitivity of 60.2% (95% CI 52.6-67.4%) and an AUC of 0.82 (95% CI 0.78-0.86). Conclusions We identified 4 strongly and independently predictive metabolites for GDM that could have clinical utility in screening for GDM.

Automated summary

By analyzing metabolomics, we identified 4 strongly and independently predictive metabolites for gestational diabetes mellitus, which could have clinical utility in screening for the condition.