Update on the genetic and epigenetic etiology of gestational diabetes mellitus: a review

TL;DR

This review summarizes recent findings on the genetic and epigenetic factors contributing to gestational diabetes mellitus (GDM), highlighting key genes, mechanisms, and implications for early detection and treatment to prevent progression to other diabetes types.

Contribution

It provides an updated overview of 83 candidate genes and epigenetic factors involved in GDM, emphasizing their role in disease pathophysiology and potential targets for intervention.

Findings

Identification of 83 GDM candidate genes, including TCF7L2, MTNR1B, CDKAL1, IRS1, and KCNQ1.

Genetic polymorphisms influence beta-cell function, obesity, and insulin resistance.

Environmental factors can induce epigenetic changes affecting glucose metabolism.

Abstract

Background: Many studies have been conducted on the genetic and epigenetic etiology of gestational diabetes mellitus (GDM) in the last two decades because of the diseases increasing prevalence and role in the global diabetes mellitus (DM) explosion. An update on the genetic and epigenetic etiology of GDM then becomes imperative to better understand and stem the rising incidence of the disease. This review, therefore, articulated GDM candidate genes and their pathophysiology for the awareness of stakeholders. Main body (genetic and epigenetic etiology, GDM): The search discovered 83 GDM candidate genes, of which TCF7L2, MTNR1B, CDKAL1, IRS1, and KCNQ1 are the most prevalent. Certain polymorphisms of these genes can modulate beta-cell dysfunction, adiposity, obesity, and insulin resistance through several mechanisms. Environmental triggers such as diets, pollutants, and microbes may also cause epigenetic changes in these genes, resulting in a loss of insulin-boosting and glucose metabolism functions. Early detection and adequate management may resolve the condition after delivery; otherwise, it will progress to maternal type 2 diabetes mellitus (T2DM) and fetal configuration to future obesity and DM. This shows that GDM is a strong risk factor for T2DM and, in rare cases, type 1 diabetes mellitus (T1DM) and maturity-onset diabetes of the young (MODY). This further shows that GDM significantly contributes to the rising incidence and burden of DM worldwide and its prevention may reverse the trend. Conclusion: Mutations and epigenetic changes in certain genes are strong risk factors for GDM. For affected individuals with such etiologies, medical practitioners should formulate drugs and treatment procedures that target these genes and their pathophysiology.