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Background <p>Gestational diabetes mellitus (GDM) is a common pregnancy-related complication, diagnosed through prenatal screening, and is associated with adverse obstetric outcomes. Women with GDM and their offspring are at a higher lifetime risk of developing type 2 diabetes mellitus (T2DM). While several factors have been independently studied, a comprehensive understanding of the combined role of genetic, epigenetic, and non-genetic factors influencing GDM and its transgenerational impact remains limited.</p> Objective <p>To provide an in-depth review of the complex interplay between genetic variants (SNPs), epigenetic mechanisms (DNA methylation, histone modifications, miRNAs), and non-genetic factors such as diet, gut microbiome, lifestyle, environmental triggers, and psychosocial determinants contributing to GDM and its role in increasing transgenerational diabetes risk.</p> Methods <p>A comprehensive literature search was conducted using relevant keywords in databases including PubMed, Scopus, Springer Nature Link, ResearchGate, and Google Scholar, as well as government and health organisation websites such as the NIH and Ministry of Health and Family Welfare, Government of India. Studies involving human participants, animal models, and investigations of genetic, epigenetic, and environmental risk factors for GDM were included. Articles were selected based on scientific relevance, data quality, and contribution to understanding GDM’s pathophysiology and intergenerational implications.</p> Results <p>The review highlights how genetic predisposition, epigenetic regulation, and non-genetic influences, including nutrition, gut ecosystem, physical activity, persistent organic pollutants, and maternal health factors, collectively modulate GDM onset and progression. The synergistic effect of these factors contributes to a heightened transgenerational risk of T2DM, emphasizing the need for targeted interventions during pregnancy and postpartum care.</p> Conclusion <p>Early diagnosis and timely management of GDM through appropriate medication, regular screening, lifestyle modifications, and physical activity can significantly reduce complications and lower intergenerational diabetes risk. Future research integrating genetic epidemiology, pathophysiology, and nutrigenetics is essential to unravel the complex mechanisms underlying GDM and to develop personalised prevention and treatment strategies.</p>

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Unraveling gestational diabetes mellitus: a review of genetic, epigenetic, and non-genetic influences

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • S. Tamil Malar,
  • Sachdev Meenakshi,
  • Anjalakshi Chandrasekar,
  • Pavithra Amritkumar

摘要

Background

Gestational diabetes mellitus (GDM) is a common pregnancy-related complication, diagnosed through prenatal screening, and is associated with adverse obstetric outcomes. Women with GDM and their offspring are at a higher lifetime risk of developing type 2 diabetes mellitus (T2DM). While several factors have been independently studied, a comprehensive understanding of the combined role of genetic, epigenetic, and non-genetic factors influencing GDM and its transgenerational impact remains limited.

Objective

To provide an in-depth review of the complex interplay between genetic variants (SNPs), epigenetic mechanisms (DNA methylation, histone modifications, miRNAs), and non-genetic factors such as diet, gut microbiome, lifestyle, environmental triggers, and psychosocial determinants contributing to GDM and its role in increasing transgenerational diabetes risk.

Methods

A comprehensive literature search was conducted using relevant keywords in databases including PubMed, Scopus, Springer Nature Link, ResearchGate, and Google Scholar, as well as government and health organisation websites such as the NIH and Ministry of Health and Family Welfare, Government of India. Studies involving human participants, animal models, and investigations of genetic, epigenetic, and environmental risk factors for GDM were included. Articles were selected based on scientific relevance, data quality, and contribution to understanding GDM’s pathophysiology and intergenerational implications.

Results

The review highlights how genetic predisposition, epigenetic regulation, and non-genetic influences, including nutrition, gut ecosystem, physical activity, persistent organic pollutants, and maternal health factors, collectively modulate GDM onset and progression. The synergistic effect of these factors contributes to a heightened transgenerational risk of T2DM, emphasizing the need for targeted interventions during pregnancy and postpartum care.

Conclusion

Early diagnosis and timely management of GDM through appropriate medication, regular screening, lifestyle modifications, and physical activity can significantly reduce complications and lower intergenerational diabetes risk. Future research integrating genetic epidemiology, pathophysiology, and nutrigenetics is essential to unravel the complex mechanisms underlying GDM and to develop personalised prevention and treatment strategies.