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Gestational diabetes mellitus: genetic factors, epigenetic alterations, and microbial composition

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Abstract

Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body’s microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.

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Fig. 1

(Modified from the IDF Diabetes Atlas, IDF 2021, with the permission of the IDF Atlas team)

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No new data were created or analysed in this study. Data sharing is not applicable to this article.

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Acknowledgements

The authors would like to thank the National Council for Science and Technology (CONACYT) for the doctoral scholarship granted to Dennise Lizárraga.

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Authors and Affiliations

  1. Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico

    Dennise Lizárraga, Anaguiven Ávalos-Soriano & Alejandra García-Gasca

  2. Laboratory of Microbial Genomics, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico

    Bruno Gómez-Gil

  3. Laboratory of Molecular and Cellular Biology, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Avenida de las Ciencias s/n, 76230, Juriquilla, Querétaro, Mexico

    Teresa García-Gasca

  4. Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy

    Livio Casarini

  5. Maternal-Fetal Department, Instituto Vidalia, Hospital Sharp Mazatlán, Avenida Rafael Buelna y Dr. Jesús Kumate s/n, 82126, Mazatlán, Sinaloa, Mexico

    Azucena Salazar-Oroz

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DL and AGG contributed to preparation, edition, and revision of the manuscript. BGG, TGG, AAS, and LC contributed to deep revision of the manuscript, according to their main areas of expertise. ASO added a clinical perspective to the review.

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Correspondence to Alejandra García-Gasca.

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Lizárraga, D., Gómez-Gil, B., García-Gasca, T. et al. Gestational diabetes mellitus: genetic factors, epigenetic alterations, and microbial composition. Acta Diabetol 61, 1–17 (2024). https://doi.org/10.1007/s00592-023-02176-y

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