Metabolomic Identification of a Novel, Externally Validated Predictive Test for Gestational Diabetes Mellitus.
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Authors
Publication Date
2022-07-14Journal Title
J Clin Endocrinol Metab
ISSN
0021-972X
Publisher
The Endocrine Society
Type
Article
This Version
AM
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Sovio, U., Clayton, G. L., Cook, E., Gaccioli, F., Charnock-Jones, D. S., Lawlor, D. A., & Smith, G. C. (2022). Metabolomic Identification of a Novel, Externally Validated Predictive Test for Gestational Diabetes Mellitus.. J Clin Endocrinol Metab https://doi.org/10.1210/clinem/dgac240
Abstract
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/m2. 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/m2 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 × 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). CONCLUSIONS: We identified 4 strongly and independently predictive metabolites for GDM that could have clinical utility in screening for GDM.
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Is supplemented by: https://doi.org/10.17863/CAM.79918
Sponsorship
This work was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme), the Medical Research Council (United Kingdom; 1100221 to G.C.S.S. and D.S.C.-J) and the NIHR Cambridge Clinical Research Facility. D.A.L.’s contribution to this study is supported by the University of Bristol and UK Medical Research Council (MM_UU_00011/3), US National Institutes of Health (R01 DK10324), European Research Council via Advanced Grant 669545, the British Heart Foundation (AA/18/7/34219 and CH/F/20/90003), the NIHR Bristol Biomedical Research Centre and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733206 (LifeCycle) funds G.L.C.’s salary. BiB receives core funding from the Wellcome Trust (WT101597MA), a joint grant from the UK Medical and Economic and Social Science Research Councils (MR/N024397/1), British Heart Foundation (CS/16/4/32482), and the National Institute for Health Research under its Applied Research Collaboration for Yorkshire and Humber and Clinical Research Network research delivery support.
Funder references
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (G1100221)
Embargo Lift Date
2023-04-18
Identifiers
External DOI: https://doi.org/10.1210/clinem/dgac240
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336230
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