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.

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妊娠和妊娠糖尿病风险中的血浆脂质组学概况：一项多种族/种族队列的前瞻性研究

简介脂代谢紊乱与妊娠糖尿病（GDM）有关。但是，关于种族/种族差异人群中脂质组学和GDM风险的前瞻性研究很少。在这里，我们的目的是（1）识别与早期GDM风险相关的妊娠早期至妊娠中期的脂质网络，以及（2）检查脂质网络与血糖生物标志物的关联，以了解其潜在机制。研究设计和方法这项研究包括107例使用Carpenter和Coustan标准确诊的GDM病例和214例来自美国国家儿童健康与人类发展研究所胎儿生长研究-辛格尔顿队列的非GDM匹配对照，420种代谢物的非靶向脂质组学数据（含328注解）和92个未注释的），在访问0（10-14周）和访问1（15-26周）时获得有关母体血浆中血糖生物标志物的信息。我们使用加权相关网络分析技术构建了脂质网络。我们使用线性混合效应模型检查了脂质网络和单个脂质与GDM风险的前瞻性关联。此外，我们在两次研究访问中都计算了与GDM相关的脂质网络和单个脂质与血浆葡萄糖，胰岛素，C肽和糖化血红蛋白之间的Pearson偏相关性。结果脂质网络的主要特征是血浆甘油二酯水平升高，饱和/低不饱和甘油三酯短，血浆胆固醇酯，鞘磷脂和磷脂酰胆碱水平降低，与发生GDM的风险较高相关（假发现率（FDR）<0.05）。在单个脂质中，发生GDM的女性与未发生GDM的女性之间，访视0的58种代谢物和访视1的96种代谢物（两个时间点均为40种代谢物）存在显着差异（FDR <0.05）。此外，GDM相关的脂质网络和单个脂质与母体血糖指标显示出一致的相关性，尤其是在第0次就诊时的妊娠早期。结论结论妊娠早期血浆脂质代谢产物在各个网络中的单独或交互作用与随后种族/种族差异的GDM风险相关美国妇女。有必要进行进一步的研究来评估脂质代谢产物作为GDM的病原学标志。GDM相关的脂质网络和单个脂质显示出与母体血糖指标的一致性，尤其是在第0次就诊时的妊娠早期。结论在种族/种族差异的美国女性中，妊娠早期血浆脂质代谢产物在各个网络中的单独和交互作用均与随后的GDM风险相关。有必要进行进一步的研究来评估脂质代谢产物作为GDM的病原学标志。GDM相关的脂质网络和单个脂质显示出与母体血糖指标的一致相关性，特别是在第0次就诊时的妊娠早期。结论种族/种族差异的美国女性在妊娠早期的血浆脂质代谢产物在单独的网络中或以单独的方式相互作用都与随后的GDM风险相关。 。有必要进行进一步的研究来评估脂质代谢产物作为GDM的病原学标志。