Ulla Sovio, Gemma L Clayton, Emma Cook, Francesca Gaccioli, D Stephen Charnock-Jones, Deborah A Lawlor, Gordon C S Smith
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 8, August 2022, Pages e3479–e3486
https://doi.org/10.1210/clinem/dgac240
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/m2.
To improve the prediction of GDM using metabolomics.
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/m2 in the POP study.
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 × 10−12, 2.2 × 10−13, 6.9 × 10−28, and 2.6 × 10−17, respectively). In the POP study, BMI > 30 kg/m2 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).
We identified 4 strongly and independently predictive metabolites for GDM that could have clinical utility in screening for GDM.
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