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

Lizárraga, Dennise; Gómez-Gil, Bruno; García-Gasca, Teresa; Ávalos-Soriano, Anaguiven; Casarini, Livio; Salazar-Oroz, Azucena; García-Gasca, Alejandra

doi:10.1007/s00592-023-02176-y

Cited by 2 publications

(4 citation statements)

References 176 publications

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“…The research underscores the profound impact of GDM on maternal and fetal health. The excessive presence of glucose, fatty acids, and amino acids in maternal circulation can lead to the development of larger-than-average fetuses, posing risks during delivery and increasing the likelihood of cesarean sections ( 42 ). Moreover, the metabolic dysregulation associated with GDM, marked by hyperglycemia and insulin resistance, can instigate a cascade of adverse effects ( 42 ).…”

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

“…The excessive presence of glucose, fatty acids, and amino acids in maternal circulation can lead to the development of larger-than-average fetuses, posing risks during delivery and increasing the likelihood of cesarean sections ( 42 ). Moreover, the metabolic dysregulation associated with GDM, marked by hyperglycemia and insulin resistance, can instigate a cascade of adverse effects ( 42 ). This metabolic upheaval not only heightens the oxygen demand but also induces chronic hypoxia and inflammation, contributing to further complications.…”

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

“…Moreover, the repercussions of GDM extend far beyond pregnancy. Both mothers who experience GDM and their offspring face an elevated risk of developing type 2 diabetes, obesity, and cardiovascular conditions later in life ( 42 ). While genetic factors undoubtedly play a role, it’s crucial to recognize the multifaceted nature of GDM’s etiology.…”

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

“…Recent studies have delved into the intricate interplay between genetics, epigenetics, environmental factors, and the body’s microbiota in predisposing individuals to GDM ( 43 , 44 ). ( 42 ) demonstrated that the surplus of glucose, fatty acids, and amino acids characteristic of GDM contributes to fetal macrosomia, chronic hypoxia, and inflammation, underscoring the multifactorial nature of its pathogenesis. Moreover, investigation by ( 10 ) has highlighted the role of epigenetic mechanisms and environmental factors in predisposing individuals to GDM, further reinforcing the complexity of its etiology.…”

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

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Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Ray,

Zeng,

Kusi

et al. 2024

Front. Endocrinol.

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Gestational diabetes mellitus (GDM) poses a significant global health concern, impacting both maternal and fetal well-being. Early detection and treatment are imperative to mitigate adverse outcomes during pregnancy. This review delves into the pivotal role of insulin function and the influence of genetic variants, including SLC30A8, CDKAL1, TCF7L2, IRS1, and GCK, in GDM development. These genetic variations affect beta-cell function and insulin activity in crucial tissues, such as muscle, disrupting glucose regulation during pregnancy. We propose a hypothesis that this variation may disrupt zinc transport, consequently impairing insulin production and secretion, thereby contributing to GDM onset. Furthermore, we discussed the involvement of inflammatory pathways, such as TNF-alpha and IL-6, in predisposing individuals to GDM. Genetic modulation of these pathways may exacerbate glucose metabolism dysregulation observed in GDM patients. We also discussed how GDM affects cardiovascular disease (CVD) through a direct correlation between pregnancy and cardiometabolic function, increasing atherosclerosis, decreased vascular function, dyslipidemia, and hypertension in women with GDM history. However, further research is imperative to unravel the intricate interplay between inflammatory pathways, genetics, and GDM. This understanding is pivotal for devising targeted gene therapies and pharmacological interventions to rectify genetic variations in SLC30A8, CDKAL1, TCF7L2, IRS1, GCK, and other pertinent genes. Ultimately, this review offers insights into the pathophysiological mechanisms of GDM, providing a foundation for developing strategies to mitigate its impact.

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Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

Section: The Role Of Genetic Factors In the Development Of Gestationa...mentioning

confidence: 99%

See 2 more Smart Citations

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Ray,

Zeng,

Kusi

et al. 2024

Front. Endocrinol.

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Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring

Wang,

Cui,

Yang

2024

BMC Microbiol

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Gestational diabetes mellitus (GDM) is characterized by insulin resistance and low-grade inflammation, and most studies have demonstrated gut dysbiosis in GDM pregnancies. Overall, they were manifested as a reduction in microbiome diversity and richness, depleted short chain fatty acid (SCFA)-producing genera and a dominant of Gram-negative pathogens releasing lipopolysaccharide (LPS). The SCFAs functioned as energy substance or signaling molecules to interact with host locally and beyond the gut. LPS contributed to pathophysiology of diseases through activating Toll-like receptor 4 (TLR4) and involved in inflammatory responses. The gut microbiome dysbiosis was not only closely related with GDM, it was also vital to fetal health through vertical transmission. In this review, we summarized gut microbiota signature in GDM pregnancies of each trimester, and presented a brief introduction of microbiome derived SCFAs. We then discussed mechanisms of microbiome-host interactions in the physiopathology of GDM and associated metabolic disorders. Finally, we compared offspring microbiota composition from GDM with that from normal pregnancies, and described the possible mechanism.

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

Cited by 2 publications

References 176 publications

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring

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