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Recent Advance in Gestational Diabetes-Over Life Course and across Generations

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 5086

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Special Issue Editors

Prof. Dr. Cuilin Zhang

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Guest Editor

Yong Loo Lin School of Medicine, National Univeristy of Singapore, Singapore, Singapore
Interests: nutrition and lifestyle; omics research; maternal and child health; women’s health; genetic and metabolic determinants and health consequences of obesity; gestational diabetes and type 2 diabetes and related comorbidities; developmental origins of diseases
Special Issues, Collections and Topics in MDPI journals

Dr. Katherine A. Bowers

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Guest Editor

1. Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
2. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Interests: pregnancy; gestational diabetes; offspring outcomes; neurodevelopment

Special Issue Information

Dear Colleagues,

Gestational diabetes mellitus (GDM) is associated with short- and long-term adverse health outcomes in women and their offspring, and is at the center of the “diabetes begetting diabetes” transgenerational circle. Breaking this vicious cycle is not hopeless. Effective early screening to identify women at high risk and timely intervention may represent a promising approach. Emerging omics technologies and other new technologies have the potential to improve the prediction of GDM and the monitoring of the long-term health of mothers and offspring.

In this Special Issue we call for papers on recent advances in GDM, with a particular focus on the application of novel risk factors, biomarkers, omics technology (e.g., genetics. epigenetics, metabolomics, and microbiome), wearable devices, and mobile technology to advance research on the following aspects.

Novel risk factors and prediction of GDM;
Interventions to prevent GDM;
Novel risk factors and prediction of life-long adverse health outcomes related to GDM in both women and offspring, and strategies to prevent and delay the onset of these complications.

Studies among women at high risk, such as Hispanics and Asians, are encouraged.

Prof. Dr. Cuilin Zhang
Dr. Katherine A. Bowers
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

biomarkers
genetics
epigenetics
metabolomics
microbiome
novel technology
wearable device
prediction
prevention
novel risk factors

Published Papers (3 papers)

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Research

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15 pages, 1773 KiB

Open AccessArticle

Maternal Serum Metabolomics in Mid-Pregnancy Identifies Lipid Pathways as a Key Link to Offspring Obesity in Early Childhood

by Ellen C. Francis, Katerina Kechris, Randi K. Johnson, Shristi Rawal, Wimal Pathmasiri, Blake R. Rushing, Xiuxia Du, Thomas Jansson, Dana Dabelea, Susan J. Sumner and Wei Perng

Int. J. Mol. Sci. 2024, 25(14), 7620; https://doi.org/10.3390/ijms25147620 (registering DOI) - 11 Jul 2024

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Abstract

Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference (n = 360); High HDL-C (n = 289); Dyslipidemic–High TG (n = 149); Dyslipidemic–High FFA (n = 180); Insulin Resistant (IR)–Hyperglycemic (n = 87). These subgroups not only captured metabolic heterogeneity among pregnant participants but were also associated with offspring obesity in early childhood, even among women without obesity or diabetes. Here, we utilize metabolomics data to enrich characterization of the metabolic subgroups and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 pregnant women at 18 gestational weeks using untargeted metabolomics. We used weighted gene correlation network analysis (WGCNA) to derive a global network based on the Reference subgroup and characterized distinct metabolite modules representative of the different metabolomic profiles. We used the mummichog algorithm for pathway enrichment and identified key compounds that differed across the subgroups. Eight metabolite modules representing pathways such as the carnitine–acylcarnitine translocase system, fatty acid biosynthesis and activation, and glycerophospholipid metabolism were identified. A module that included 189 compounds related to DHA peroxidation, oxidative stress, and sex hormone biosynthesis was elevated in the Insulin Resistant–Hyperglycemic vs. the Reference subgroup. This module was positively correlated with total cholesterol (R:0.10; p-value < 0.0001) and free fatty acids (R:0.07; p-value < 0.05). Oxidative stress and inflammatory pathways may underlie insulin resistance during pregnancy, even below clinical diabetes thresholds. These findings highlight potential therapeutic targets and strategies for pregnancy risk stratification and reveal mechanisms underlying the developmental origins of metabolic disease risk. Full article

(This article belongs to the Special Issue Recent Advance in Gestational Diabetes-Over Life Course and across Generations)

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10 pages, 1399 KiB

Open AccessArticle

miR-24-3p and Body Mass Index as Type 2 Diabetes Risk Factors in Spanish Women 15 Years after Gestational Diabetes Mellitus Diagnosis

by Jessica Ares Blanco, Carmen Lambert, Manuel Fernandez-Sanjurjo, Paula Morales-Sanchez, Pedro Pujante, Paola Pinto-Hernández, Eduardo Iglesias-Gutiérrez, Edelmiro Menendez Torre and Elias Delgado

Int. J. Mol. Sci. 2023, 24(2), 1152; https://doi.org/10.3390/ijms24021152 - 6 Jan 2023

Cited by 4 | Viewed by 2048

Abstract

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance that is diagnosed for the first time during pregnancy. The objective of this study is to know the glucose tolerance status after 15 years of pregnancy in patients diagnosed with gestational diabetes and to assess the long-term effect of GDM on the circulating miRNA profile of these women. To answer these, 30 randomly selected women diagnosed with GDM during 2005–2006 were included in the study, and glucose tolerance was measured using the National Diabetes Data Group criteria. Additionally, four miRNAs (hsa-miR-1-3p, hsa-miR-24-3p, hsa-miR-329-3p, hsa-miR-543) were selected for their analysis in the plasma of women 15 years after the diagnosis of GDM. In our study we discovered that, fifteen years after the diagnosis of GDM, 50% of women have some degree of glucose intolerance directly related to body weight and body mass index during pregnancy. Dysglycemic women also showed a significantly increased level of circulating hsa-miR-24-3p. Thus, we can conclude that initial weight and BMI, together with circulating expression levels of hsa-miR-24-3p, could be good predictors of the future development of dysglycemia in women with a previous diagnosis of GDM. Full article

(This article belongs to the Special Issue Recent Advance in Gestational Diabetes-Over Life Course and across Generations)

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Review

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Open AccessReview

Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes

by William L. Lowe, Jr.

Int. J. Mol. Sci. 2023, 24(7), 6047; https://doi.org/10.3390/ijms24076047 - 23 Mar 2023

Cited by 4 | Viewed by 2350

Abstract

Gestational diabetes (GDM) is one of the most common complications of pregnancy, affecting as many as one in six pregnancies. It is associated with both short- and long-term adverse outcomes for the mother and fetus and has important implications for the life course of affected women. Advances in genetics and epigenetics have not only provided new insight into the pathophysiology of GDM but have also provided new approaches to identify women at high risk for progression to postpartum cardiometabolic disease. GDM and type 2 diabetes share similarities in their pathophysiology, suggesting that they also share similarities in their genetic architecture. Candidate gene and genome-wide association studies have identified susceptibility genes that are shared between GDM and type 2 diabetes. Despite these similarities, a much greater effect size for MTNR1B in GDM compared to type 2 diabetes and association of HKDC1, which encodes a hexokinase, with GDM but not type 2 diabetes suggest some differences in the genetic architecture of GDM. Genetic risk scores have shown some efficacy in identifying women with a history of GDM who will progress to type 2 diabetes. The association of epigenetic changes, including DNA methylation and circulating microRNAs, with GDM has also been examined. Targeted and epigenome-wide approaches have been used to identify DNA methylation in circulating blood cells collected during early, mid-, and late pregnancy that is associated with GDM. DNA methylation in early pregnancy had some ability to identify women who progressed to GDM, while DNA methylation in blood collected at 26–30 weeks gestation improved upon the ability of clinical factors alone to identify women at risk for progression to abnormal glucose tolerance post-partum. Finally, circulating microRNAs and long non-coding RNAs that are present in early or mid-pregnancy and associated with GDM have been identified. MicroRNAs have also proven efficacious in predicting both the development of GDM as well as its long-term cardiometabolic complications. Studies performed to date have demonstrated the potential for genetic and epigenetic technologies to impact clinical care, although much remains to be done. Full article

(This article belongs to the Special Issue Recent Advance in Gestational Diabetes-Over Life Course and across Generations)

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