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Precision integrated identification of predictive first-trimester metabolomics signatures for early detection of gestational diabetes mellitus.
Sharma, Sapna Subrahmanyam, Yalamanchili Venkata Gupta, Payal Vadivel, Sangeetha Deepa, Mohan Tandon, Ansh Sreedevi, Sreekumar Ram, Uma Narad, Priyanka Parmar, Dharmeshkumar
Sharma, Sapna
Subrahmanyam, Yalamanchili Venkata
Gupta, Payal
Vadivel, Sangeetha
Deepa, Mohan
Tandon, Ansh
Sreedevi, Sreekumar
Ram, Uma
Narad, Priyanka
Parmar, Dharmeshkumar
Affiliation
German Research Center for Environmental Health, Neuherberg, Germany; CSIR-National Chemical Laboratory, Pune, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India; George Eliot Hospital NHS Trust, Nuneaton; et al.
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Publication date
2025-11-14
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Abstract
BACKGROUND AND AIM: Gestational diabetes mellitus (GDM), a common pregnancy-related metabolic disorder, often goes undiagnosed until the second trimester, limiting early intervention opportunities. Given the higher prevalence of GDM in India, there is a critical need to investigate metabolomic biomarkers among Asian Indians, who exhibit greater insulin resistance and are predisposed to developing type 2 diabetes at an earlier age. This study aimed to identify early pregnancy metabolomic signatures predictive of GDM.
METHODS: Among 2115 pregnant women from the STratification of Risk of Diabetes in Early pregnancy (STRiDE) study, we performed untargeted metabolomic profiling using UPLC-MS/MS at early pregnancy (< 16 weeks) plasma samples from 100 women-comprising 50 with GDM and 50 normal (without GDM) based on oral glucose tolerance test (OGTT) at 24-28 weeks. Statistical and machine learning approaches, including logistic regression and random forest (RF), were applied to identify GDM-associated metabolites and construct predictive models. Pathway enrichment analysis was conducted using KEGG database annotations.
RESULTS: A total of 49 metabolites were significantly associated with GDM, primarily involving lipid classes such as phosphatidylcholines, sphingomyelins, and triacylglycerols. RF analysis identified a panel of eight metabolites that achieved best predictive performance (AUC 0.880; 95% CI: 0.809-0.951) for GDM. When combined with conventional clinical risk factors, the integrated model showed comparable prediction of GDM with AUC 0.88;: 95% CI: 0.810-0.952). Enrichment analysis highlighted dysregulated pathways including glycerophospholipid and sphingolipid metabolism, autophagy, and insulin resistance.
CONCLUSION: This study demonstrates the utility of early-pregnancy metabolomic profiling for predicting GDM in Indian women. The eight-metabolite panel offers a promising tool for early risk stratification of GDM, warranting validation in diverse populations.
Citation
Sharma S, Subrahmanyam YV, Gupta P, Vadivel S, Deepa M, Tandon A, Sreedevi S, Ram U, Narad P, Parmar D, Anjana RM, Raghunathan A, Balasubramanyam M, Mohan V, Sengupta A, Adamski J, Saravanan P, Panchagnula V, Usharani D, Gokulakrishnan K. Precision integrated identification of predictive first-trimester metabolomics signatures for early detection of gestational diabetes mellitus. Cardiovasc Diabetol. 2025 Nov 14;24(1):434. doi: 10.1186/s12933-025-02978-0.
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Article
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