Introduction Disruption of lipid metabolism is implicated in gestational diabetes (GDM). However, prospective studies on lipidomics and GDM risk in race/ethnically diverse populations are sparse. Here, we aimed to (1) identify lipid networks in early pregnancy to mid-pregnancy that are associated with subsequent GDM risk and (2) examine the associations of lipid networks with glycemic biomarkers to understand the underlying mechanisms. Research design and methods This study included 107 GDM cases confirmed using the Carpenter and Coustan criteria and 214 non-GDM matched controls from the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton cohort, untargeted lipidomics data of 420 metabolites (328 annotated and 92 unannotated), and information on glycemic biomarkers in maternal plasma at visit 0 (10-14 weeks) and visit 1 (15-26 weeks). We constructed lipid networks using weighted correlation network analysis technique. We examined prospective associations of lipid networks and individual lipids with GDM risk using linear mixed effect models. Furthermore, we calculated Pearson's partial correlation for GDM-related lipid networks and individual lipids with plasma glucose, insulin, C-peptide and glycated hemoglobin at both study visits. Results Lipid networks primarily characterized by elevated plasma diglycerides and short, saturated/low unsaturated triglycerides and lower plasma cholesteryl esters, sphingomyelins and phosphatidylcholines were associated with higher risk of developing GDM (false discovery rate (FDR) <0.05). Among individual lipids, 58 metabolites at visit 0 and 96 metabolites at visit 1 (40 metabolites at both time points) significantly differed between women who developed GDM and who did not (FDR <0.05). Furthermore, GDM-related lipid networks and individual lipids showed consistent correlations with maternal glycemic markers particularly in early pregnancy at visit 0. Conclusions Plasma lipid metabolites in early pregnancy both individually and interactively in distinct networks were associated with subsequent GDM risk in race/ethnically diverse US women. Future research is warranted to assess lipid metabolites as etiologic markers of GDM.
Bibliographical noteFunding Information:
staff at all participating clinical centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton Cohort, including Christina Care Health Systems; University of California, Irvine; Long Beach Memorial Medical Center; Northwestern University; Medical University of South Carolina; Columbia University; New York Hospital Queens; St Peters’ University Hospital; University of Alabama at Birmingham; Women & Infants Hospital of Rhode Island; Fountain Valley Regional Hospital and Medical Center and Tufts University. The authors would also like to thank the C-TASC Corporation that provided data coordination and the NIH West Coast Metabolomics Center, UC Davis Genome Center, Davis, California that provided laboratory resources essential for biochemical analysis funded by NIH ES030158 (to OF).
Funding This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding (contract numbers HHSN275200800013C, HHSN275200800002I, HHSN27500006, HHSN275200800003IC, HHSN275200800014C, HHSN275200800012C, HHSN275200800028C, HHSN275201000009C and HHSN275201000001Z).
© Where applicable, author(s) (or their employer(s)) 2021. Re-use permitted under [CC BY]. Published by BMJ.
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