Abstract
Introduction
Gestational diabetes mellitus (GDM) significantly increases maternal and fetal health risks, but factors predictive of GDM are poorly understood.
Objectives
Plasma metabolomics analyses were conducted in early pregnancy to identify potential metabolites associated with prediction of GDM.
Methods
Sixty-eight pregnant women with overweight/obesity from a clinical trial of a lifestyle intervention were included. Participants who developed GDM (n = 34; GDM group) were matched on treatment group, age, body mass index, and ethnicity with those who did not develop GDM (n = 34; Non-GDM group). Blood draws were completed early in pregnancy (10–16 weeks). Plasma samples were analyzed by UPLC-MS using three metabolomics assays.
Results
One hundred thirty moieties were identified. Thirteen metabolites including pyrimidine/purine derivatives involved in uric acid metabolism, carboxylic acids, fatty acylcarnitines, and sphingomyelins (SM) were different when comparing the GDM vs. the Non-GDM groups (p < 0.05). The most significant differences were elevations in the metabolites’ hypoxanthine, xanthine and alpha-hydroxybutyrate (p < 0.002, adjusted p < 0.02) in GDM patients. A panel consisting of four metabolites: SM 14:0, hypoxanthine, alpha-hydroxybutyrate, and xanthine presented the highest diagnostic accuracy with an AUC = 0.833 (95% CI: 0.572686–0.893946), classifying as a “very good panel”.
Conclusion
Plasma metabolites mainly involved in purine degradation, insulin resistance, and fatty acid oxidation, were altered in early pregnancy in connection with subsequent GDM development.
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Change history
19 December 2021
A Correction to this paper has been published: https://doi.org/10.1007/s11306-021-01863-7
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Acknowledgements
We thank Rodrigo Rosario, Megan McNairn, Manny Ramos, Anna Lamb, Cooper Ray, and Mikenna Corry of California Polytechnic State University, San Luis Obispo, CA for their assistance with data processing.
Funding
NIH National Heart, Lung, and Blood Institute (NHLBI; HL114377), California State University Agricultural Research Institute [grant number 18–03-011], 2020 and 2021 Doris Howell Foundation – California State University Program for Education and Research in Biotechnology (CSUPERB) Research Scholar Awards, and the Cal Poly College of Agriculture Food and Environmental Sciences (CAFES) Summer Undergraduate Research Program (SURP). The work was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare Nº075-15–2020-926”.
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EJ, RW, SP, MRL conceived and designed research; LEM, RF, NA, AQD, MRL performed experiments; LEM, HH, CMJ, AS, AB, MRL analyzed data; LEM, HH, CMJ, KP AB, SP, MRL interpreted results of experiments; HH, CMJ prepared Figures; LEM, HH, AB, and MRL drafted the manuscript; LEM, HH, KP, AS, AB. SP, MRL edited and revised manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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McMichael, L.E., Heath, H., Johnson, C.M. et al. Metabolites involved in purine degradation, insulin resistance, and fatty acid oxidation are associated with prediction of Gestational diabetes in plasma. Metabolomics 17, 105 (2021). https://doi.org/10.1007/s11306-021-01857-5
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DOI: https://doi.org/10.1007/s11306-021-01857-5