胎便中与妊娠糖尿病相关的代谢标志物的多个因素。

Multiple elements related to metabolic markers in the context of gestational diabetes mellitus in meconium.

机构信息

Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China; University of Chinese Academy of Sciences, Beijing, China.

Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, China.

出版信息

Environ Int. 2018 Dec;121(Pt 2):1227-1234. doi: 10.1016/j.envint.2018.10.044. Epub 2018 Oct 29.

DOI:10.1016/j.envint.2018.10.044

PMID:30385065

Abstract

BACKGROUND

Gestational diabetes mellitus (GDM) is a typical fetus development niches dysfunction and many toxic/nutrient elements have been associated with its onset and progression. However, the classic epidemiologic approach is regarded as "black-box epidemiology" and fails to elucidate these elements' biological roles on the damaged fetus developmental microenvironment.

OBJECTIVE

We aimed to characterize the associations between meconium of multiple elements with GDM for illustrating their interruption effects on in-uterus microenvironment.

METHODS

In this case-control study (n = 137 cases; n = 197 controls), the participants were nested from a cross-sectional retrospection of 1359 recruitments in Xiamen, China. Twenty-one meconium elements were characterized using inductively coupled plasma mass spectrometry (ICP-MS) or inductively coupled plasma optical emission spectrometry (ICP-OES). For shifting the present paradigm from a black-box approach to a molecular approach, GDM-related metabolic markers were identified in our previous metabolome report. Based on the meet-in-middle strategy, the associations among the elements, metabolic markers and GDM incidence were assessed by using redundancy analysis and correlation-adjusted correlation; mediation analysis was further used to test the hypothesis that metabolic markers mediate the associations of the elements with GDM incidence.

RESULTS

Eight elements were related with the GDM occurrence in dose-dependent manners, which positively (Al, As, Ba, Cd, Hg, and Sn) or negatively (Ca and V) associated with GDM. Among them, As, Cd, Ba, and Ca significantly contributed to the variation of GDM-related metabolic markers. Additionally, the associations of Cd, Ba, Ca and As with GDM were mediated by the metabolic markers which majorly involved in the lipid metabolism and the Adenosine/l-Arginine/Nitric Oxide (ALANO) pathways.

CONCLUSIONS

The two-side mediations of meconium metabolic markers between the multiple elements and GDM occurrence indicated that maternal exposure to As, Ba, Cd, and Ca may be associated with the dysfunction of fetus development niche through disrupting lipid metabolism and ALANO pathways.

摘要

背景

妊娠糖尿病（GDM）是一种典型的胎儿发育龛功能障碍，许多有毒/营养元素与 GDM 的发生和进展有关。然而，经典的流行病学方法被认为是“黑盒流行病学”，无法阐明这些元素对受损胎儿发育微环境的生物学作用。

目的

我们旨在描述多种胎粪元素与 GDM 的关联，以阐明它们对宫内微环境的中断作用。

方法

在这项病例对照研究中（病例组 n=137，对照组 n=197），参与者是从中国厦门的 1359 名招募者的横断面回顾中嵌套的。采用电感耦合等离子体质谱（ICP-MS）或电感耦合等离子体发射光谱（ICP-OES）对 21 种胎粪元素进行了特征描述。为了将目前的范式从黑盒方法转变为分子方法，我们在之前的代谢组报告中鉴定了与 GDM 相关的代谢标志物。基于中间相遇策略，采用冗余分析和相关调整相关分析评估了元素、代谢标志物与 GDM 发生率之间的关系；进一步采用中介分析来检验代谢标志物介导元素与 GDM 发生率之间关联的假设。

结果

有 8 种元素与 GDM 的发生呈剂量依赖性相关，正向（Al、As、Ba、Cd、Hg 和 Sn）或负向（Ca 和 V）与 GDM 相关。其中，As、Cd、Ba 和 Ca 与 GDM 的发生显著相关。此外，Cd、Ba、Ca 和 As 与 GDM 的关联是由代谢标志物介导的，这些代谢标志物主要涉及脂质代谢和腺苷/精氨酸/一氧化氮（ALANO）途径。