Early maternal circulating alkaline phosphatase with subsequent gestational diabetes mellitus and glucose regulation: a prospective cohort study in China

Xiong, Ting; Zhong, Chunrong; Sun, Guoqiang; Zhou, Xian; Chen, Renjuan; Li, Qian; Wu, Yuanjue; Gao, Qin; Huang, Li; Hu, Xingwen; Xiao, Mei; Yang, Xuefeng; Hao, Liping; Yang, Nianhong

doi:10.1007/s12020-019-01954-5

Cited by 11 publications

(12 citation statements)

References 32 publications

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“…Interestingly, restricted cubic spline analyses in our study showed nonlinear associations of ALT and AST with risk of GDM and the associations appeared to reach a plateau as ALT and AST elevated. Only one study that investigated the association between ALP and GDM found a linear association among 2,073 Chinese pregnant women [ 37 ], which is consistent with our findings. Intriguingly, pregnant women with elevated liver enzymes were at an increased risk of GDM even when the levels did not reach the threshold for clinical abnormalities in our work, which was reflected in other studies for ALT [ 23 ], GGT [ 24 ], and ALP [ 37 ].…”

Section: Discussionsupporting

confidence: 91%

“…Only one study that investigated the association between ALP and GDM found a linear association among 2,073 Chinese pregnant women [ 37 ], which is consistent with our findings. Intriguingly, pregnant women with elevated liver enzymes were at an increased risk of GDM even when the levels did not reach the threshold for clinical abnormalities in our work, which was reflected in other studies for ALT [ 23 ], GGT [ 24 ], and ALP [ 37 ]. While this finding should be confirmed elsewhere, it may suggest the need to routinely monitor the increase in liver enzymes in pregnant women.…”

Section: Discussionsupporting

confidence: 91%

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

Wang

et al. 2023

BMC Med

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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

Wang

et al. 2023

BMC Med

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“…Pooled results of included studies did not demonstrate a significant relationship between AST levels and OR for GDM (OR: 0.76, 95% CI: 0.52-1.10, I 2 : 16%) [29,30]. Furthermore, just one study was identified that evaluated the relationship between ALP and GDM [24] and we could therefore conduct an analysis; however, according to Xiong et al, there is a significant relation between ALP levels and OR for GDM 2.47 (95% CI 1.47, 4.15) in highest category of ALP compared to the lowest.…”

Section: Main Results Of the Meta-analysismentioning

confidence: 94%

“…Eighteen studies were evaluated in full text screening and 10 studies failed to meet inclusion criteria and were subsequently excluded. Finally, eight studies with a total of 25,451 participants were identified as eligible according to meta-analysis inclusion criteria [24][25][26][27][28][29][30][31].…”

Section: Literature Searchmentioning

confidence: 99%

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The association of plasma levels of liver enzymes and risk of gestational diabetes mellitus: a systematic review and dose–response meta-analysis of observational studies

Zhao

Zhang

et al. 2019

Acta Diabetol

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This document is the author's post-print version, incorporating any revisions agreed during the peer-review process. Some differences between the published version and this version may remain and you are advised to consult the published version if you wish to cite from it.The Association of plasma levels of liver enzymes and risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis of observational studies running head: liver enzymes and gestational diabetes mellitus

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

Cui,

Yang,

et al. 2024

Diabetes Metabolism Res

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AimsPrevious studies have found that a single liver enzyme may predict gestational diabetes mellitus (GDM), but the results have been inconsistent. This study aimed to explore the associations of liver enzymes in early pregnancy with risk of GDM, as well as to independently rank risk factors.MethodsThis prospective cohort study included 1295 women who underwent liver enzyme measurements during early pregnancy and completed GDM assessment in mid‐pregnancy. Logistic regression and restricted cubic spline analyses were conducted to assess the relationship between liver enzymes and risk of GDM. Back‐propagation artificial neural network was performed to rank independently risk factors of GDM.ResultsWomen diagnosed with GDM exhibited significantly higher levels of liver enzymes than those without GDM (all p < 0.05). The highest quartile of liver enzymes was associated with higher risk of GDM compared with the lowest quartile, with adjusted odds ratio (ORs) ranging from 2.76 to 8.11 (all p < 0.05). Moreover, the ORs of GDM increased linearly with liver enzymes level (all P for overall association <0.001). Furthermore, Back‐propagation artificial neural network identified γ‐gamma‐glutamyl transferase (GGT) as accounting for the highest proportion in the ranking of GDM risk prediction weights (up to 20.8%).ConclusionsSingle or total elevations of liver enzymes in early pregnancy could predict the GDM occurrence, in which GGT, alkaline Phosphatase, and aspartate aminotransferase were the three most important independent risk factors.

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Early maternal circulating alkaline phosphatase with subsequent gestational diabetes mellitus and glucose regulation: a prospective cohort study in China

Cited by 11 publications

References 32 publications

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

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

The association of plasma levels of liver enzymes and risk of gestational diabetes mellitus: a systematic review and dose–response meta-analysis of observational studies

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

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