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BMC Medicine
Published in: BMC Medicine 1/2023

Open Access 01-12-2023 | Gestational Diabetes | Research article

Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women

Authors: Ping Wu, Yi Wang, Yi Ye, Xue Yang, Yichao Huang, Yixiang Ye, Yuwei Lai, Jing Ouyang, Linjing Wu, Jianguo Xu, Jiaying Yuan, Yayi Hu, Yi-Xin Wang, Gang Liu, Da Chen, An Pan, Xiong-Fei Pan

Published in: BMC Medicine | Issue 1/2023

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Abstract

Background

Liver plays an important role in maintaining glucose homeostasis. We aimed to examine the associations of liver enzymes and hepatic steatosis index (HSI, a reliable biomarker for non-alcoholic fatty liver disease) in early pregnancy with subsequent GDM risk, as well as the potential mediation effects of lipid metabolites on the association between HSI and GDM.

Methods

In a birth cohort, liver enzymes were measured in early pregnancy (6-15 gestational weeks, mean 10) among 6,860 Chinese women. Multivariable logistic regression was performed to examine the association between liver biomarkers and risk of GDM. Pearson partial correlation and least absolute shrinkage and selection operator (LASSO) regression were conducted to identify lipid metabolites that were significantly associated with HSI in a subset of 948 women. Mediation analyses were performed to estimate the mediating roles of lipid metabolites on the association of HSI with GDM.

Results

Liver enzymes and HSI were associated with higher risks of GDM after adjustment for potential confounders, with ORs ranging from 1.42 to 2.24 for extreme-quartile comparisons (false discovery rate-adjusted P-trend ≤0.005). On the natural log scale, each SD increment of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and HSI was associated with a 1.15-fold (95% CI: 1.05, 1.26), 1.10-fold (1.01, 1.20), 1.21-fold (1.10, 1.32), 1.15-fold (1.04, 1.27), and 1.33-fold (1.18, 1.51) increased risk of GDM, respectively. Pearson partial correlation and LASSO regression identified 15 specific lipid metabolites in relation to HSI. Up to 52.6% of the association between HSI and GDM risk was attributed to the indirect effect of the HSI-related lipid score composed of lipid metabolites predominantly from phospholipids (e.g., lysophosphatidylcholine and ceramides) and triacylglycerol.

Conclusions

Elevated liver enzymes and HSI in early pregnancy, even within a normal range, were associated with higher risks of GDM among Chinese pregnant women. The association of HSI with GDM was largely mediated by altered lipid metabolism.
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Metadata
Title
Liver biomarkers, lipid metabolites, and risk of gestational diabetes mellitus in a prospective study among Chinese pregnant women
Authors
Ping Wu
Yi Wang
Yi Ye
Xue Yang
Yichao Huang
Yixiang Ye
Yuwei Lai
Jing Ouyang
Linjing Wu
Jianguo Xu
Jiaying Yuan
Yayi Hu
Yi-Xin Wang
Gang Liu
Da Chen
An Pan
Xiong-Fei Pan
Publication date
01-12-2023
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2023
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-023-02818-6

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