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Review
. 2024 Apr 17:15:1399694.
doi: 10.3389/fendo.2024.1399694. eCollection 2024.

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Affiliations
Review

Genetic and inflammatory factors underlying gestational diabetes mellitus: a review

Gyan Watson Ray et al. Front Endocrinol (Lausanne). .

Abstract

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.

Keywords: beta-cell dysfunction; genetic factors; genetic variations; gestational diabetes mellitus (GDM); glucose metabolism; inflammatory pathways.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
General diagnostics process of GDM identification. Source.
Figure 2
Figure 2
Different genetic factors responsible for GDM.
Figure 3
Figure 3
Impact of GDM on the mother and offspring. CS, C-Section (Cesarean delivery); GDM, gestational diabetes mellitus; T2DM, Type 2 diabetes mellitus; T1DM, Type 1 diabetes mellitus; LGA, Large for gestational age.

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