Gestational Diabetes Mellitus Affects Offspring’s Epigenome. Is There a Way to Reduce the Negative Consequences?

Słupecka-Ziemilska, Monika; Wychowański, Piotr; Puzianowska-Kuźnicka, Monika

doi:10.3390/nu12092792

Cited by 19 publications

(21 citation statements)

References 82 publications

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“…68 Third, GDM can also lead to epigenetic changes and impact the expression of genes that direct body fat accumulation or related metabolic pathways. 73,74 Thus, our findings are biologically plausible. However, our study failed to find that intensive management of GDM had discernible benefits for offspring exposed to maternal GDM.…”

Section: Discussionsupporting

confidence: 63%

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta‐analysis with more than half a million offspring

Gao

Cao

et al. 2021

Obesity Reviews

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We conducted a meta-analysis to evaluate the association of maternal gestational diabetes mellitus (GDM) and offspring overweight from birth to adulthood, and to assess the effects of lifestyle interventions in women with GDM on this risk of offspring overweight. We identified literature from PubMed and 12 other electronic databases and retrieved relevant literature published before October 20, 2020. Random-effects model analysis was used to calculate relative risks (RRs) of overweight and weighted mean differences of body mass index among children stratified into different developmental stages. Forty-nine cohort studies (n = 559,377) and four randomized controlled trials (n = 1277) were included. We found that offspring of women with GDM were at an increased risk for overweight with age, from 1.14 (95% confidence interval [CI]: 1.06-1.22) under 5 years, 1.37 (95% CI: 1.31-1.44) at 5 to <10 years, 2.00 (95% CI: 1.79-2.23) at 10 to <18 years, to 2.05 (95% CI: 1.65-2.55) over 18 years of age (p < 0.05 for differences among groups). However, it was not observed that lifestyle interventions for GDM decreased the elevated overweight risk (RR: 0.94, 95% CI: 0.80-1.11, I 2 = 0.0%). These findings highlight the need for adopting an active and healthy lifestyle in this high-risk group.

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Section: Discussionsupporting

confidence: 63%

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta‐analysis with more than half a million offspring

Gao

Cao

et al. 2021

Obesity Reviews

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“…It remains to be determined whether this is the case with the changes in HTR2A methylation observed here. Considering that most human studies have shown that female children are more susceptible to metabolic programming by maternal obesity and diabetes [ 55 , 67 ], the finding that HTR2A methylation in female placentas is more sensitive to maternal metabolic disturbances than in male placentas supports this possibility.…”

Section: Discussionmentioning

confidence: 96%

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

et al. 2022

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The serotonin receptor 2A gene (HTR2A) is a strong candidate for the fetal programming of future behavior and metabolism. Maternal obesity and gestational diabetes mellitus (GDM) have been associated with an increased risk of metabolic and psychological problems in offspring. We tested the hypothesis that maternal metabolic status affects methylation of HTR2A in the placenta. The prospective study included 199 pairs of mothers and healthy full-term newborns. Genomic DNA was extracted from feto-placental samples and analyzed for genotypes of two polymorphisms (rs6311, rs6306) and methylation of four cytosine residues (−1665, −1439, −1421, −1224) in the HTR2A promoter region. Placental HTR2A promoter methylation was higher in male than female placentas and depended on both rs6311 and rs6306 genotypes. A higher maternal pre-gestational body mass index (pBMI) and, to a lesser extent, diagnosis of GDM were associated with reduced HTR2A promoter methylation in female but not male placentas. Higher pBMI was associated with reduced methylation both directly and indirectly through increased GDM incidence. Tobacco use during pregnancy was associated with reduced HTR2A promoter methylation in male but not female placentas. The obtained results suggest that HTR2A is a sexually dimorphic epigenetic target of intrauterine exposures. The findings may contribute to a better understanding of the early developmental origins of neurobehavioral and metabolic disorders associated with altered HTR2A function.

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“…GDM is a common complication of pregnancy that has adverse effects on the short-term and long-term health of women and their children ( 91 ). Approximately 2-5% of pregnant women develop GDM during pregnancy, and the incidence rate has significantly increased over the past 10 years ( 92 ).…”

Section: Association Between Hnf1a Polymorphism and Gdmmentioning

confidence: 99%

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

Jiang

Sun

2022

Front. Endocrinol.

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Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic β cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.

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Gestational Diabetes Mellitus Affects Offspring’s Epigenome. Is There a Way to Reduce the Negative Consequences?

Cited by 19 publications

References 82 publications

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta‐analysis with more than half a million offspring

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta‐analysis with more than half a million offspring

Maternal Metabolic State and Fetal Sex and Genotype Modulate Methylation of the Serotonin Receptor Type 2A Gene (HTR2A) in the Human Placenta

HNF1A：From Monogenic Diabetes to Type 2 Diabetes and Gestational Diabetes Mellitus

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