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

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.

From Shadows to Spotlight: Exploring the Escalating Burden of Alcohol-Associated Liver Disease and Alcohol Use Disorder in Young Women

“…In this large-scale study using the GBD 2019 database depicting the burden and temporal progression of AUD and ALD in young female patients, we are witnessing an escalating prevalence of AUD and ALD. These trends mirror global increases in alcohol consumption that detrimentally affect young women's health, which are important predictors of alcohol-associated complications at the later stage of life and afflicted maternal and fetal health (25–27). In contrast to prevalence, age-adjusted death and DALYs decline in all regions and SDI strata, possibly reflecting the improvement of the healthcare system and education in many regions of the world.…”

Elevated liver enzymes in the first trimester are associated with gestational diabetes mellitus: A prospective cohort study

“…35 Therefore, increased liver en- Evidence furthermore emerged that elevated liver enzymes predict GDM in relation to fat metabolism, 37 the correlation accounted for 52.6%. 12 Third, elevated liver enzymes might also be an effect of changes in blood circulation and hormone levels during pregnancy. In conclusion, elevation of five liver enzymes in early pregnancy were positively associated with increased risk of GDM among Chinese pregnant women, with GGT, ALP, and AST being the three most significant independent risk factors.…”

“…24,25 These findings indicate that ALT/AST or AST/ALT might disturb metabolic syndrome or lipid metabolism. 12,26 The discrepancy might due to different study design, diagnostic criteria, sample size and population characteristics (maternal age, ethnicity, Gestational weeks, Lifestyle). The strong correlation in the present study might be due to the relatively older age of participants, especially now that China has liberalized its two-child, three-child policy.…”

“…13,20,27 So far, only one paper has reported the positive association of AST and the risk of GDM, which was consistent with our findings. 12 Compared with this study, we included and adjusted for more potential confounders in our work to make the results more reliable.…”

“…15 A similar study demonstrated that elevated ALT within normal range in early pregnancy predicted GDM. 16 The research on AST, ALP and ALT/AST were limited, 12,17 especially studying all five liver enzymes in early pregnancy.…”