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早孕期循环溶血磷脂酰胆碱与中国女性妊娠期糖尿病的风险

Circulating Lysophosphatidylcholines in Early Pregnancy and Risk of Gestational Diabetes in Chinese Women.

机构信息

Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.

Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin, China.

出版信息

J Clin Endocrinol Metab. 2020 Apr 1;105(4). doi: 10.1210/clinem/dgaa058.

Abstract

OBJECTIVES

This study aimed to explore associations of lysophosphatidylcholines (LPCs) in early pregnancy with gestational diabetes mellitus (GDM), and whether LPCs mediated the associations of bile acids with GDM risk or had interactive effects with bile acids on GDM risk.

DESIGN

We conducted a 1:1 nested case-control study (n = 486) from a large prospective pregnant women cohort in urban Tianjin, China. Blood samples were collected at their first antenatal care visit (median at 10th gestational week). LPCs were measured by liquid chromatography-tandem mass spectrometry analysis. Conditional binary logistic regression and restricted cubic spline analysis were used to identify cutoff points of these metabolites for GDM risk.

RESULTS

Of the 6 detectable LPCs, LPC14:0 less than 0.24 nmol/mL, LPC15:0 at 0.45 nmol/mL or greater, and LPC18:0 at 18.00 nmol/mL or greater were independently associated with GDM risk. Adjustment for LPC18:0 slightly attenuated odds ratios (ORs) of deoxycholic acid (DCA, ≤ 0.36 nmol/mL) and glycoursodeoxycholic acid (GUDCA, ≤ 0.07 nmol/mL) for GDM, and the correlations of DCA and GUDCA with LPC18:0 were weak. However, the presence of DCA at 0.36 nmol/mL or less greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 8.18 (2.51-26.7) up to 17.7 (6.64-47.1), with significant additive interaction. Similarly, the presence of GUDCA at 0.07 nmol/mL or less also greatly amplified the adjusted OR of LPC18:0 at 18.00 nmol/mL or greater alone for GDM from 17.2 (1.77-168) up to 73.8 (12.7-429), with significant additive interaction.

CONCLUSIONS

LPCs in early pregnancy were associated with GDM risk. Low DCA or GUDCA greatly amplified the effect of high LPC18:0 on GDM, and its molecular mechanism is worth further investigations.

摘要

目的

本研究旨在探讨孕早期溶血磷脂酰胆碱(LPCs)与妊娠期糖尿病(GDM)之间的关联,以及 LPCs 是否介导了胆汁酸与 GDM 风险之间的关联,或者与胆汁酸在 GDM 风险方面是否存在交互作用。

设计

我们在中国天津市的一个大型前瞻性孕妇队列中进行了 1:1 的巢式病例对照研究(n=486)。在第一次产前检查时(中位数在妊娠第 10 周)采集血样。采用液相色谱-串联质谱分析检测 LPCs。采用条件二元逻辑回归和限制性三次样条分析确定这些代谢物对 GDM 风险的截断值。

结果

在可检测的 6 种 LPC 中,LPC14:0 小于 0.24 nmol/mL、LPC15:0 大于等于 0.45 nmol/mL 和 LPC18:0 大于等于 18.00 nmol/mL 与 GDM 风险独立相关。调整 LPC18:0 后,脱氧胆酸(DCA,≤0.36 nmol/mL)和甘氨鹅脱氧胆酸(GUDCA,≤0.07 nmol/mL)与 GDM 的比值比(ORs)略有减弱,而 DCA 和 GUDCA 与 LPC18:0 的相关性较弱。然而,DCA 浓度为 0.36 nmol/mL 或更低时,大大增强了 LPC18:0 浓度为 18.00 nmol/mL 或更高时单独发生 GDM 的调整后 OR,从 8.18(2.51-26.7)增加到 17.7(6.64-47.1),具有显著的相加交互作用。同样,GUDCA 浓度为 0.07 nmol/mL 或更低时,也大大增强了 LPC18:0 浓度为 18.00 nmol/mL 或更高时单独发生 GDM 的调整后 OR,从 17.2(1.77-168)增加到 73.8(12.7-429),具有显著的相加交互作用。

结论

孕早期的 LPCs 与 GDM 风险相关。低浓度的 DCA 或 GUDCA 大大增强了高浓度 LPC18:0 对 GDM 的影响,其分子机制值得进一步研究。

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