Associations between an Integrated Component of Maternal Glycemic Regulation in Pregnancy and Cord Blood DNA Methylation

Juvinao-Quintero, Diana L.; Perron, Patrice; Bouchard, Luigi; Lutz, Sharon M.; Hivert, Marie‐France

doi:10.2217/epi-2021-0220

Cited by 3 publications

(3 citation statements)

References 61 publications

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“…found no evidence for robust associations between maternal prenatal glucose and insulin levels and offspring cord blood DNA methylation. However, significant associations were identified between a higher AUC gluc and hypomethylation at cg26974062 and cg02988288 (located within TXNIP ) ( 26 , 110 , 111 ). High heterogeneity was found for these associations, hypothesized to be due to the effect of management of hyperglycaemia in the third trimester on cord blood DNA methylation, as was noted during a randomized lifestyle intervention trial during pregnancy ( 12 ).…”

Section: Subsectionsmentioning

confidence: 95%

“…TXNIP indirectly encodes the GLUT1 receptor in the presence of glucose ( 110 ) and its expression is mediated by activation of ChREBP in pancreatic β-cells, regulating insulin production, hepatic glucose synthesis and peripheral glucose uptake. TXNIP is also highly expressed in AT and is upregulated in prediabetes ( 111 ). TXNIP is the most replicated DNA methylation marker associated with T2D, indeed alterations at TXNIP may also occur in response to obesity or hyperlipidaemia prior to the onset of T2D ( 112 ).…”

Section: Subsectionsmentioning

confidence: 99%

“…TXNIP indirectly encodes the GLUT1 receptor in the presence of glucose (110) and its expression is mediated by activation of ChREBP in pancreatic b-cells, regulating insulin production, hepatic glucose synthesis and peripheral glucose uptake. TXNIP is also highly expressed in AT and is upregulated in prediabetes (111).…”

Section: Maternal Epigenetic Modifications In Gdmmentioning

confidence: 99%

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Multigenerational diabetes mellitus

Thornton,

Shah,

Lillycrop

et al. 2024

Front. Endocrinol.

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Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing the risk of short- and long-term adverse outcomes for both mother and child. Children of mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease and GDM when they themselves become pregnant, perpetuating a multigenerational increased risk of metabolic disease. The negative effect of GDM is exacerbated by maternal obesity, which induces a greater derangement of fetal adipogenesis and growth. Multiple factors, including genetic, epigenetic and metabolic, which interact with lifestyle factors and the environment, are likely to contribute to the development of GDM. Genetic factors are particularly important, with 30% of women with GDM having at least one parent with T2D. Fetal epigenetic modifications occur in response to maternal GDM, and may mediate both multi- and transgenerational risk. Changes to the maternal metabolome in GDM are primarily related to fatty acid oxidation, inflammation and insulin resistance. These might be effective early biomarkers allowing the identification of women at risk of GDM prior to the development of hyperglycaemia. The impact of the intra-uterine environment on the developing fetus, “developmental programming”, has a multisystem effect, but its influence on adipogenesis is particularly important as it will determine baseline insulin sensitivity, and the response to future metabolic challenges. Identifying the critical window of metabolic development and developing effective interventions are key to our ability to improve population metabolic health.

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Section: Subsectionsmentioning

confidence: 95%

Section: Subsectionsmentioning

confidence: 99%

Section: Maternal Epigenetic Modifications In Gdmmentioning

confidence: 99%

See 1 more Smart Citation

Multigenerational diabetes mellitus

Thornton,

Shah,

Lillycrop

et al. 2024

Front. Endocrinol.

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Maternal Metabolic Health, Lifestyle, and Environment – Understanding How Epigenetics Drives Future Offspring Health

Amrom

Schwartz

2023

CDR

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The incidence of metabolic disorders such as obesity and type two diabetes (T2DM) continues to increase worldwide, and their onset is often attributed to adherence to a western diet and a sedentary lifestyle. However, a large variability exists in one's likelihood of developing metabolic dysregulation, illustrating that our understanding of heritability patterns remains poorly understood. Diabetes and obesity are multifactorial diseases, and their onset is influenced by both genetic and environmental factors. Genome-wide association studies reported a number of alterations in the coding sequence associated with the onset of T2DM and obesity. However, these genes explain only a fraction of the cases, leaving the majority unaccounted for. The missing heritability question implies that other factors are responsible for the onset and development of the disease. Given that the developing fetus is susceptible to the maternal environment, a growing body of evidence demonstrates that maternal metabolic characteristics as well as disruptions to the prenatal environment may induce long-term genetic, phenotypic, and physiologic adaptations in the developing fetus, which could have a permanent effect on its future health. This phenomenon is known as developmental programming and is mediated through epigenetic modifications, which include modulation of gene expression that do not alter the original deoxyribonucleic (DNA) sequence. Epigenetic modifications are capable of changing gene expression in metabolism-related genes and are accomplished through DNA methylation, histone acetylation, and ribonucleic acid (RNA) mechanisms. In this review, we discuss maternal metabolic factors such as obesity, dyslipidemia, and gestational diabetes (GDM) that lead to epigenetic changes in the offspring and predispose future generations to metabolic abnormalities. We will also describe the association between maternal lifestyle factors and exposure to toxins with epigenetic modulations in the offspring. Lastly, we will provide a brief review of the possibility of using epigenetics as potential interventions and therapeutic modalities to help with early diagnosis and prevention of metabolic disorders.

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Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study

et al. 2022

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Although there are some epigenome-wide association studies (EWAS) of insulin resistance, most of them did not replicate their findings and are focused in populations of European ancestry limiting the generalizability. In EPIPREG (294 Europeans and 162 South Asians), we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in Born in Bradford (n=879; 430 Europeans and 449 South Asians), MENA (n=320) and Botnia (n=56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, whereof five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP, cg06690548 in SLC7A11, cg04861640 in ZSCAN26). From methylation quantitative trait loci analysis in EPIPREG, we identified gene variants related to all five replicated cross-ancestry CpG sites, which were associated with several cardiometabolic phenotypes. Mediation analyses suggested that the gene variants regulate insulin resistance through DNA methylation. To conclude, our cross-ancestry EWAS identified five CpG sites related with lower insulin resistance.

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Associations between an Integrated Component of Maternal Glycemic Regulation in Pregnancy and Cord Blood DNA Methylation

Cited by 3 publications

References 61 publications

Multigenerational diabetes mellitus

Multigenerational diabetes mellitus

Maternal Metabolic Health, Lifestyle, and Environment – Understanding How Epigenetics Drives Future Offspring Health

Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy: An Integrative Epigenome-Wide Association Study

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