Epigenetic Modification of the Pentose Phosphate Pathway and the Igf-Axis in Women with Gestational Diabetes Mellitus

Steyn, Angela; Crowther, Nigel J; Norris, Shane A.; Rabionet, Raquel; Estivill, Xavier; Ramsay, Michèle

doi:10.2217/epi-2018-0206

Cited by 16 publications

(21 citation statements)

References 47 publications

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“…Promoter region DNA methylation was examined for chosen genes and correlated with gene expression to examine epigenetic modifications. Reduced mRNA expression and increased DNA methylation were found for G6PD in GDM patients, and for genes encoding insulin-like growth factor (IGF)-binding proteins in GDM placentas [ 59 ].…”

Section: Epigenetics In Gdmmentioning

confidence: 99%

Epigenetic Changes in Gestational Diabetes Mellitus

Dłuski

Wolińska

Skrzypczak

2021

IJMS

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Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that appears or is for the first time diagnosed during pregnancy. It can lead to many complications in the mother and in the offspring, so diagnostics and management of GDM are important to avoid adverse pregnancy outcomes. Epigenetic studies revealed the different methylation status of genes in pregnancies with GDM compared to pregnancies without GDM. A growing body of evidence shows that the GDM can affect not only the course of the pregnancy, but also the development of the offspring, thus contributing to long-term effects and adverse health outcomes of the progeny. Epigenetic changes occur through histone modification, DNA methylation, and disrupted function of non-coding ribonucleic acid (ncRNA) including microRNAs (miRNAs). In this review, we focus on the recent knowledge about epigenetic changes in GDM. The analysis of this topic may help us to understand pathophysiological mechanisms in GDM and find a solution to prevent their consequences.

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Section: Epigenetics In Gdmmentioning

confidence: 99%

Epigenetic Changes in Gestational Diabetes Mellitus

Dłuski

Wolińska

Skrzypczak

2021

IJMS

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“…associated with maternal glucose levels at fasting and 1 hr, but not at 2 hrs, post OGTT. Only females Steyn et al, 2019 [ 96 ] 32 GDM 31 Ctrl 450k EWAS OAS1, PPIA, POLR2G 24,577 CpG sites with changes of DNAm (without FDR). Pathway analysis identified OAS1, PPIA and POLR2G as possible pathogenic genes of GDM, based on protein-protein interaction analysis.…”

Section: Introductionmentioning

confidence: 99%

Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps

et al. 2022

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SUMMARY Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in pregnancies complicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy outcome, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in pregnancies complicated by diabetes and obesity.

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“…Global DNAm is altered during hyperglycemia ( 34 , 35 ), and increased global methylation in placental tissue has been associated with GDM ( 36 , 37 ). However, there are limited data describing DNAm in the peripheral blood of patients with GDM, and the results are inconclusive ( 16-19 , 21 , 22 , 38 , 39 ). Small sample sizes and the absence of reproducibility or confirmatory cohorts have been the main weaknesses in most studies ( 16-18 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances

Ballesteros

Gil-Lluís

Ejarque

et al. 2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context DNA methylation in the diagnosis of gestational diabetes Objective To assess the value of DNA methylation in the diagnosis of gestational diabetes (GDM) and in the prediction of maternal postpartum glucose disturbances. Design Two-stage observational between July 2006 and December 2010. Setting University Hospital Patients Forty-eight randomly selected pregnant women formed the discovery cohort (24 with GDM and 24 controls) and 252 pregnant women (94 with GDM and 158 controls) formed the replication cohort. GDM women were re-evaluated 4 years postpartum. Main Outcome Measures GDM, type 2 diabetes or prediabetes at 4 years postpartum Results We identified three CpG sites related to LINC00917, TRAPPC9 and LEF1 that were differentially methylated in women with GDM and abnormal glucose tolerance, and the sites associated with LINC00917 and TRAPPC9 were independently associated with an abnormal glucose tolerance status four-years postpartum after controlling for clinical variables. Moreover, the site associated with LINC00917 and the combination of the three sites had the highest predictive values. Conclusions Our results suggest that some of these sites may be implicated in the development of GDM and postpartum abnormal glucose tolerance.

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Epigenetic Modification of the Pentose Phosphate Pathway and the Igf-Axis in Women with Gestational Diabetes Mellitus

Cited by 16 publications

References 47 publications

Epigenetic Changes in Gestational Diabetes Mellitus

Epigenetic Changes in Gestational Diabetes Mellitus

Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps

DNA Methylation in Gestational Diabetes and its Predictive Value for Postpartum Glucose Disturbances

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