The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus

Rosik, Jakub; Szostak, Bartosz; Machaj, Filip; Pawlik, Andrzej

doi:10.1111/ahg.12356

Cited by 52 publications

(50 citation statements)

References 100 publications

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“…Hyperglycemia during pregnancy endangers maternal health and has adverse effects on the fetus (7). A large number of studies at home and abroad indicate that exploring the risk factors affecting the pregnancy outcomes of GDM patients and providing targeted intervention measures have an important clinical value for improving the pregnancy outcomes of GDM patients (8).…”

Section: Discussionmentioning

confidence: 99%

The relationship between changes in vitamin A, vitamin E, and oxidative stress levels, and pregnancy outcomes in patients with gestational diabetes mellitus

Qiao

et al. 2021

Ann Palliat Med

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Background: Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy. This study aims to analyze the relationship between the changes in vitamin A, vitamin E, and oxidative stress levels, and pregnancy outcomes in GDM patients.Methods: A total of 104 GDM patients admitted to our hospital between January 2018 and January 2019 were selected as the study group, and 126 pregnant women who received healthy examinations in the same hospital during the same period were selected as the control group. Vitamin A, E, and oxidative stress [total antioxidant capacity (TAOC), malondialdehyde (MDA), red blood cell glutathione (GSH), and superoxide dismutase (SOD)] between the two groups were compared. Age, pre-pregnancy body mass index (BMI), prepregnancy waist-to-hip ratio (waist/hip circumference), parity, gravidity, glycosylated hemoglobin, and other related index levels were collected for the GDM patients. Multivariate logistic regression analysis was used to analyze the risk factors affecting the pregnancy outcomes of the GDM patients.Results: The levels of vitamin A, SOD, GSH, and TAOC in the study group were significantly lower than those in the control group, and the levels of vitamin E and MDA were significantly higher than those in the control group (P<0.05). Of the 104 GDM patients, 43 had adverse pregnancy outcomes, and 61 had no adverse pregnancy outcomes. There was a significant difference between the adverse and non-adverse pregnancy outcome groups in the levels of glycosylated hemoglobin, vitamin A, vitamin E, MDA, SOD, GSH, and TAOC (P<0.05). Analysis of the unconditional multivariate logistic regression model showed that the expression levels of glycosylated hemoglobin, vitamin A, vitamin E, MDA, SOD, GSH, and TAOC were independent risk factors affecting the pregnancy outcomes of GDM patients (P<0.05).Conclusions: Vitamin A, E, and oxidative stress levels are abnormally expressed in GDM, and are independent risk factors affecting the pregnancy outcomes in GDM patients. Therefore, the clinical monitoring of oxidative stress levels and vitamin supplementation should be increased, as these may be of great significance in improving pregnancy outcomes in GDM patients.

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Section: Discussionmentioning

confidence: 99%

The relationship between changes in vitamin A, vitamin E, and oxidative stress levels, and pregnancy outcomes in patients with gestational diabetes mellitus

Qiao

et al. 2021

Ann Palliat Med

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“…The fact that a Genome Wide Association Study (GWAS) performed in a South Korean cohort reported a strong association with GDM of several SNPs in different genes that were already known to be T2DM susceptibility genes [26] supports the strong genetic overlap between both forms of diabetes. Interestingly, the majority of loci associated with GDM impact β-cell function [27]. Nevertheless, the association with GDM was not demonstrated by all T2DM associated loci [28], suggesting that the effect size of the genetic variants could be different between the two conditions and that some of the identified loci could be specific to each disease.…”

Section: Etiology Of Gdm and Genetic Component Of The Diseasementioning

confidence: 99%

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Lorenzo

Martín-Montalvo

Vuilleumier

et al. 2019

IJMS

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Gestational diabetes mellitus (GDM), a metabolic disease that develops with the increase in insulin resistance during late pregnancy, is currently one of the most common complications affecting pregnancy. The polygenic nature of GDM, together with the interplay between different genetic variants with nutritional and environmental factors has hindered the full understanding of the etiology of this disease. However, an important genetic overlap has been found with type 2 diabetes mellitus (T2DM) and, as in the case of T2DM, most of the identified loci are associated with β-cell function. Early detection of GDM and adequate interventions to control the maternal glycemia are necessary to avoid the adverse outcomes for both the mother and the offspring. The in utero exposure to the diabetic milieu predispose these children for future diseases, among them T2DM, originating a vicious circle implicated in the increased prevalence of both GDM and T2DM. The involvement of inflammatory processes in the development of GDM highlights the importance of pancreatic β-cell factors able to favor the adaptation processes required during gestation, concomitantly with the protection of the islets from an inflammatory milieu. In this regard, two members of the Pax family of transcription factors, PAX4 and PAX8, together with the chromatin remodeler factor HMG20A, have gained great relevance due to their involvement in β-cell mass adaptation together with their anti-inflammatory properties. Mutations in these factors have been associated with GDM, highlighting these as novel candidates for genetic screening analysis in the identification of women at risk of developing GDM.

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“…The underlying factors leading to the development of GDM are difficult to determine, and may involve a combination of diverse environmental, genetic, and epigenetic factors. An increasing amount of evidence points to a connection between genetics and GDM [2].…”

Section: Introductionmentioning

confidence: 99%

Lack of association between IGF2BP2 rs4402960 polymorphism and gestational diabetes mellitus: a case–control study, meta-analysis and trial sequential analysis

et al. 2020

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Background It is well known that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs4402960 polymorphism is associated with type 2 diabetes mellitus, which has a shared genetic background with gestational diabetes mellitus (GDM). Previous studies have yielded controversial results about the link between IGF2BP2 rs4402960 polymorphism and GDM risk. Thus, a meta-analysis was performed to obtain more conclusive results. Methods Clinical and genotype data were determined for 305 GDM and 1216 healthy participants recruited. Eligible studies were retrieved in PubMed, Web of science, EMBASE, and Scopus. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to evaluate the relationship between IGF2BP2 polymorphisms and GDM susceptibility in five genetic models. The subgroup stratified analysis and trial sequential analysis (TSA) were performed. Results In this case-control study, no significant association was revealed between IGF2BP2 polymorphism and GDM (P > 0.05). When combined with the previous studies in the meta-analysis, there was no statistical association between IGF2BP2 polymorphism and GDM (allele model: OR = 1.01, 95% CI = 0.86–1.18; dominant model: OR = 1.00, 95% CI = 0.81–1.24; recessive model: OR = 1.08, 95% CI = 0.91–1.29; heterozygous model: OR = 0.99, 95% CI = 0.80–1.24; homozygous model: OR = 1.06, 95% CI = 0.78–1.42). No association was observed in five genetic models in each subgroup. TSA indicated sufficient proof of such null association in the overall population. Conclusions This meta-analysis provides sufficient statistical evidence indicating null association between IGF2BP2 rs4402960 polymorphism and GDM risk.

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The role of genetics and epigenetics in the pathogenesis of gestational diabetes mellitus

Cited by 52 publications

References 100 publications

The relationship between changes in vitamin A, vitamin E, and oxidative stress levels, and pregnancy outcomes in patients with gestational diabetes mellitus

The relationship between changes in vitamin A, vitamin E, and oxidative stress levels, and pregnancy outcomes in patients with gestational diabetes mellitus

Molecular Modelling of Islet β-Cell Adaptation to Inflammation in Pregnancy and Gestational Diabetes Mellitus

Lack of association between IGF2BP2 rs4402960 polymorphism and gestational diabetes mellitus: a case–control study, meta-analysis and trial sequential analysis

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