Journal Article

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

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

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Alanine / Alanine transaminase / Alcohol use / Alkaline phosphatase / Analysis / Aspartate aminotransferase / Biological markers / Biomarkers / Biomedicine / Birth cohort / Care and treatment / Cholesterol / Diabetes in pregnancy / Diabetes mellitus / Diabetes, Gestational - epidemiology / Diabetes, Gestational - etiology / Diagnosis / East Asian People / Enzymes / Fatty liver / Female / fetal and childhood outcomes / Gestational age / Gestational diabetes / Gestational diabetes mellitus / Glucose / Health aspects / Health risks / Hepatic steatosis index / Homeostasis / Humans / Insulin resistance / Laboratories / Lipid metabolism / Lipidomics / Lipids / Liver / Liver diseases / Liver enzyme / Lysophosphatidylcholine / Maternal factors during pregnancy influencing maternal / Medicine / Medicine & Public Health / Metabolites / Phospholipids / Pregnancy / Pregnancy complications / Pregnant Women / Prevention / Prospective Studies / Regression / Research Article / Risk / Risk Factors / Steatosis / Transaminases / Triglycerides / Variables / Womens health / γ-Glutamyltransferase