Maternal liver dysfunction in early pregnancy predisposes to gestational diabetes mellitus independent of preconception overweight: A prospective cohort study

Chen, Xiaotian; Chen, Hongyan; Zhang, Yi; Jiang, Yuan; Wang, Yin; Huang, Xiangyuan; Wang, Dingmei; Li, Mengru; Dou, Yalan; Sun, Xupeng; Huang, Guoying; Yan, Weili

doi:10.1111/1471-0528.17117

Cited by 9 publications

(17 citation statements)

References 30 publications

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“…Prior studies have examined the association of liver enzyme levels and its development of adverse pregnancy outcomes, such as GDM and pre-eclampsia. [16][17][18][19][20] By itself, liver enzyme levels, such as ALT, are poor predictors of MAFLD. 21 As such, non-invasive indices of hepatic steatosis may be a simple measure (over imaging) used to assess for probable MAFLD.…”

Section: Discussionmentioning

confidence: 99%

“…Most studies have focused on liver enzymes collected either pre-gravid 16,17 or during pregnancy. [18][19][20] The inclusion of pre-gravid AST and ALT in our study was important as prior studies have determined that abnormal values were associated with the development of adverse maternal outcomes, such as GDM or pre-eclampsia. 16,17 Whilst a majority of studies analysed liver enzyme levels during pregnancy and determined associations with adverse pregnancy outcomes, [18][19][20] liver enzyme levels can change during the course of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] The inclusion of pre-gravid AST and ALT in our study was important as prior studies have determined that abnormal values were associated with the development of adverse maternal outcomes, such as GDM or pre-eclampsia. 16,17 Whilst a majority of studies analysed liver enzyme levels during pregnancy and determined associations with adverse pregnancy outcomes, [18][19][20] liver enzyme levels can change during the course of pregnancy. Whilst AST levels did not significantly change between matched pregnant and non-pregnant women, ALT levels were slightly elevated (although remained within reference limits) in second-trimester pregnant women.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study

Chai¹,

George²,

Pasupathy³

et al. 2023

IJWH

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Objective To determine whether an elevated hepatic steatosis index (HSI), a non-invasive test for possible metabolic dysfunction-associated fatty liver disease (MAFLD), is associated with the development of adverse pregnancy outcomes. Material and Methods A retrospective cohort study was conducted on adult women with singleton pregnancies who delivered at two tertiary hospitals from August 2014 to December 2017. Aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) levels obtained 12 months pre-gravid, or during pregnancy but prior to screening for gestational diabetes mellitus (GDM), were extracted and linked with oral glucose tolerance test results. The HSI was calculated using the following equation: 8 × (ALT/AST ratio) + BMI (+2 if female; +2 if diabetes mellitus present) and considered elevated if >36. Multiple logistic regression analysis was used to quantify the association between elevated HSI and each composite adverse pregnancy outcome after adjusting for independent maternal risk factors. Results Over 40-months, 11929 women were eligible and of these, 1885 had liver enzymes collected. Women with an elevated HSI (>36) were more likely multiparous and overweight/obese compared to those women with a non–elevated HSI (≤36). Elevated HSI was significantly associated with a composite of adverse maternal outcomes (adjusted odds ratio (aOR) 1.55 95% CI 1.11–2.17, p =0.01), although a non-significant increased risk of a composite of adverse neonatal outcomes occurred after multivariable adjustment (aOR 1.17, 95% CI 0.94–1.45, p =0.17). Conclusion Over and above known maternal risk factors, women with elevated HSI were more likely to develop adverse maternal, but not adverse neonatal outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study

Chai¹,

George²,

Pasupathy³

et al. 2023

IJWH

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“…Unfortunately, imaging examinations or diagnoses of liver steatosis and cholestasis are not available in our study. Several observational studies have reported the signi cant association of maternal GGT and ALP levels in early pregnancy with the development of gestational diabetes between 24-28 gestation weeks 32,33 . Our novel ndings add new evidence to the relationship between maternal GGT, ALP levels, and SPL risk, and provide a clue that maternal liver steatosis or cholestasis maybe two of the possible underlying mechanisms for the development of SPL.…”

Section: Discussionmentioning

confidence: 99%

Maternal Abnormal Liver Function in Early Pregnancy and Spontaneous Pregnancy Loss: A Retrospective Cohort Study

Yang,

Tang,

Zhang

et al. 2023

Preprint

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Background Spontaneous pregnancy loss (SPL) precedes an increased risk of reduced fertility, while its etiology mechanism remains largely unknown. Liver dysfunction presenting in early pregnancy may represent a pre-existing undiagnosed liver condition affecting foetal development. As a common but easily to be neglected metabolic disorder, little is known about whether and how maternal abnormal liver function in early pregnancy contribute to the incidence of SPL. Methods This is retrospective cohort study included 10175 pregnant womenwho were leveraged from the Maternal Health Care Information System (MHCIS) in Shanghai City from Jan 2017 to Dec 2021. Maternal liver dysfunction status was defined as having any elevated liver function biomarker levels (LFBs) at the first antenatal visit. SPL cases were defined as fetal death occurring before 28 weeks gestation. Generalized linear models with binomial family and log link function were used to estimate crude and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs). Results Among 10175 leveraged pregnant women, 918 (9.0%) SPL cases were recorded. Maternal liver dysfunction in early pregnancy was associated with a 49% increased risk of SPL (RR 1.49, 95% CI 1.22–1.84). This positive association persisted after adjustment for covariates (aRR 1.55, 95% CI 1.26–1.92). Higher γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) levels were also linked with increased risk of SPL in a linear fashion (aRRs per 1 standard deviation increase: 1.13, 95% CI 1.08–1.17; 1.13, 1.07–1.20, respectively). These observed positive associations remained significant even after adjustment for multiple corrections. Similar magnitudes of associations between liver dysfunction and SPL were observed in the subgroups of normal weight and overweight pregnant women. Conclusions We provide new evidence that maternal abnormal liver function in early pregnancy, as well as GGT and APL, predisposes to an increased risk of SPL. Primary healthcare providers may need to offer appropriate preconception counseling on the management of this modifiable risk factor in women of reproductive age.

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“…The liver, a target organ of IR-related diseases such as GDM and T2DM, exhibits dysfunction in the early pregnancy, which can increase the risk of GDM in the pregnancy period [12,13].…”

Section: Introductionmentioning

confidence: 99%

Adipose stem cells-derived small extracellular vesicles transport Thrombospondin 1 cargo to promote insulin resistance in gestational diabetes mellitus

Li,

Yang,

Liu

et al. 2023

Preprint

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Background Gestational diabetes mellitus (GDM) is a highly prevalent disease and poses a significant risk to the health of pregnant women. Abdominal adipose tissue (AT) contributes to insulin resistance (IR) associated with GDM. However, the underlying mechanisms remain unclear. Methods In this study, we developed a mouse model of GDM by subjecting mice to a high-fat diet. We collected adipose-derived stem cells (ADSCs) from the abdominal and inguinal regions and examined their role in inducing IR in normal tissues through the secretion of small extracellular vesicles (sEVs). The sEVs derived from ADSCs isolated from GDM mice (ADSC/GDM) were found to inhibit cell viability and insulin sensitivity in AML12, a normal mouse liver cell line. Results Through proteomic analysis, we identified high levels of the thrombospondin 1 (Thbs1) protein in the sEVs derived from ADSC/GDM. Subsequent overexpression of Thbs1 protein in AML12 cells demonstrated similar IR as observed with ADSC/GDM-derived sEVs. Mechanistically, the Thbs1 protein within the sEVs interacted with CD36 and transforming growth factor (Tgf) β receptors in AML12 cells, leading to the activation of Tgfβ/Smad2 signaling. Furthermore, the administration of LSKL, an antagonistic peptide targeting Thbs1, suppressed Thbs1 expression in ADSC/GDM-derived sEVs, thereby restoring insulin sensitivity in AML12 cells and GDM mice in vivo. Conclusions These findings shed light on the intercellular transmission mechanism through which ADSCs influence hepatic insulin sensitivity and underscore the therapeutic potential of targeting the Thbs1 protein within sEVs.

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Maternal liver dysfunction in early pregnancy predisposes to gestational diabetes mellitus independent of preconception overweight: A prospective cohort study

Cited by 9 publications

References 30 publications

Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study

Elevated Hepatic Steatosis Index is Associated with the Development of Adverse Maternal, but Not Adverse Neonatal, Outcomes: A Retrospective Cohort Study

Maternal Abnormal Liver Function in Early Pregnancy and Spontaneous Pregnancy Loss: A Retrospective Cohort Study

Adipose stem cells-derived small extracellular vesicles transport Thrombospondin 1 cargo to promote insulin resistance in gestational diabetes mellitus

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