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

Gestational diabetes mellitus (GDM) is the most common pregnancy complication worldwide and may result in short-term and long-term consequences for offspring. The present review highlights evidence of epigenetic programming, mostly from human studies, which occurs in offspring exposed to maternal GDM during different stages of development, paying special attention to the differences in sensitivity of offspring to maternal hyperglycemia as a result of sex-related factors. We also aim to answer the following question: If these epigenetic changes are constant throughout the lifetime of the offspring, how do they present phenotypically?

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Epigenetic Changes in Gestational Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22147649 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7649

Author(s):

Dominik Franciszek Dłuski ◽

Ewa Wolińska ◽

Maciej Skrzypczak

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Methylation Status ◽

Epigenetic Changes ◽

Long Term Effects ◽

Adverse Health Outcomes ◽

Adverse Pregnancy ◽

First Time

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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Breastfeeding Duration and Development of Dysglycemia in Women Who Had Gestational Diabetes Mellitus: Evidence from the GUSTO Cohort Study

Nutrients ◽

10.3390/nu13020408 ◽

2021 ◽

Vol 13 (2) ◽

pp. 408

Author(s):

Sumali S. Hewage ◽

Xin Yu Hazel Koh ◽

Shu E. Soh ◽

Wei Wei Pang ◽

Doris Fok ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Tolerance Test ◽

Diabetes Risk ◽

Breastfeeding Duration ◽

Oral Glucose ◽

Inverse Association ◽

Index Pregnancy

(1) Background: Breastfeeding has been shown to support glucose homeostasis in women after a pregnancy complicated by gestational diabetes mellitus (GDM) and is potentially effective at reducing long-term diabetes risk. (2) Methods: Data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study were analyzed to understand the influence of breastfeeding duration on long-term dysglycemia (prediabetes and diabetes) risk in women who had GDM in the index pregnancy. GDM and dysglycemia four to seven years postpartum were determined by the oral glucose tolerance test (OGTT). A Poisson regression model with a robust error variance was used to estimate incidence rate ratios (IRRs) for dysglycemia four to seven years post-delivery according to groupings of the duration of any breastfeeding (<1, ≥1 to <6, and ≥6 months). (3) Results: Women who had GDM during the index pregnancy and complete breastfeeding information and OGTT four to seven years postpartum were included in this study (n = 116). Fifty-one women (44%) had postpartum dysglycemia. Unadjusted IRRs showed an inverse association between dysglycemia risk and ≥1 month to <6 months (IRR 0.91; 95% confidence interval [CI] 0.57, 1.43; p = 0.68) and ≥6 months (IRR 0.50; 95% CI 0.27, 0.91; p = 0.02) breastfeeding compared to <1 month of any breastfeeding. After adjusting for key confounders, the IRR for the ≥6 months group remained significant (IRR 0.42; 95% CI 0.22, 0.80; p = 0.008). (4) Conclusions: Our results suggest that any breastfeeding of six months or longer may reduce long-term dysglycemia risk in women with a history of GDM in an Asian setting. Breastfeeding has benefits for mothers beyond weight loss, particularly for those with GDM.

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Lactation Duration and Long-term Risk for Incident Type 2 Diabetes in Women With a History of Gestational Diabetes Mellitus

Diabetes Care ◽

10.2337/dc19-2237 ◽

2020 ◽

Vol 43 (4) ◽

pp. 793-798 ◽

Cited By ~ 8

Author(s):

Sylvia H. Ley ◽

Jorge E. Chavarro ◽

Mengying Li ◽

Wei Bao ◽

Stefanie N. Hinkle ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Incident Type ◽

Incident Type 2 Diabetes ◽

History Of ◽

Lactation Duration

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Long Term Predictors of Post-Partum Glucose Metabolism in Women with Gestational Diabetes Mellitus

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0030-1249634 ◽

2010 ◽

Vol 118 (08) ◽

pp. 485-489 ◽

Cited By ~ 4

Author(s):

G. Seghieri ◽

F. Tesi ◽

A. De Bellis ◽

R. Anichini ◽

G. Fabbri ◽

...

Keyword(s):

Diabetes Mellitus ◽

Glucose Metabolism ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Post Partum

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Recent Advances in Gestational Diabetes Mellitus

Journal of Clinical Medicine ◽

10.3390/jcm10102202 ◽

2021 ◽

Vol 10 (10) ◽

pp. 2202

Author(s):

Katrien Benhalima

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Clinical Medicine ◽

Metabolic Risk ◽

Special Issue ◽

Recent Advances ◽

Adverse Pregnancy ◽

New Biomarkers

The incidence of gestational diabetes mellitus (GDM) and overt diabetes in pregnancy is rising globally. GDM leads to increased risks for maternal and neonatal adverse pregnancy outcomes. In addition, GDM is also associated with an increased long-term metabolic risk in mothers and offspring [1]. Although much is known about GDM, evidence gaps persist. For instance, more research is needed on how to prevent GDM, on whether screening and treatment of GDM in early pregnancy are beneficial, on non-fasting biomarkers to screen for GDM, on new biomarkers to predict pregnancy complications, and on how to reduce the long-term metabolic risk in mothers and infants after delivery. To address this important health issue, the present Special Issue in the Journal of Clinical Medicine was dedicated to recent advances in the field of GDM. This Special Issue published 16 articles on this topic. [...]

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Iron-Related Factors in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus: the Ma’anshan Birth Cohort (MABC) Study

Biological Trace Element Research ◽

10.1007/s12011-018-1595-4 ◽

2018 ◽

Vol 191 (1) ◽

pp. 45-53 ◽

Cited By ~ 4

Author(s):

Beibei Zhu ◽

Chunmei Liang ◽

Xun Xia ◽

Kun Huang ◽

Shuangqin Yan ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Birth Cohort ◽

Early Pregnancy ◽

Related Factors ◽

Subsequent Risk

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Changes of serum zinc-α2-glycoprotein level and analysis of its related factors in gestational diabetes mellitus:a cross-sectional study

10.21203/rs.3.rs-30602/v1 ◽

2020 ◽

Author(s):

Caiying Feng ◽

Jie You ◽

Guixia Chen ◽

Hongli Su ◽

Li Zhang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Serum Zinc ◽

Cross Sectional Study ◽

Control Group ◽

Study Group ◽

Clinical Trial Registry ◽

Related Factors ◽

Cross Sectional

Abstract Background Previous studies have discovered that zinc-α2-glycoprotein is related to insulin resistance and lipid metabolism. The aim of the study is to explore the change of serum zinc-α2-glycoprotein(ZAG) and its related factors in gestational diabetes mellitus(GDM). Methods Eighty newly diagnosed GDM patients were enrolled in study group, and 80 normal pregnant women were selected as control group. The differences of baseline data between the two groups were compared, and the change of serum ZAG level and its relationship with related indexes was analyzed. Results Compared to control group, the level of serum ZAG in the study group decreased [(43.94 ± 14.51)mg/L vs. (62.57 ± 19.05)mg/L, P < 0.001]. Pearson correlation (or Spearman correlation) analysis showed that serum ZAG level was negatively correlated with FPG, FINS, HOMA-IR and TG (P < 0.05) and positively correlated with HDL(P < 0.05). Multiple linear regression showed that HDL, FINS, HOMA-IR were independent factors of serum ZAG(P < 0.001). Conclusion The level of serum ZAG in patients with gestational diabetes mellitus decreased, and HDL, FINS and HOMA-IR are the influencing factors in study group. Trial registration: The study registered in the Chinese Clinical Trial Registry(Chi CTR2000028811).

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Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia

Frontiers in Endocrinology ◽

10.3389/fendo.2021.690648 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yoshifumi Kasuga ◽

Tomoko Kawai ◽

Kei Miyakoshi ◽

Yoshifumi Saisho ◽

Masumi Tamagawa ◽

...

Keyword(s):

Diabetes Mellitus ◽

Dna Methylation ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Start Site ◽

Epigenetic Changes ◽

Neonatal Hypoglycaemia ◽

Transcription Start ◽

Cpg Sites ◽

Alternative Transcription

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

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