Cellular and molecular overview of gestational diabetes mellitus: Is it predictable and preventable?

Background: In contrast to overt diabetes mellitus (DM), gestational DM (GDM) is defined as impaired glucose tolerance induced by pregnancy, which may arise from exaggerated physiologic changes in glucose metabolism. GDM prevalence is reported to be as high as 20% among pregnancies depending on the screening method, gestational age, and the population studied. Maternal and fetal effects of uncontrolled GDM include stillbirth, macrosomia, neonatal diabetes, birth trauma, and subsequent postpartum hemorrhage. Therefore, it is essential to find the potential target population and associated predictive and preventive measures for future intensive peripartum care.

Aim: To review studies that explored the cellular and molecular mechanisms of GDM as well as predictive measures and prevention strategies.

Methods: The search was performed in the Medline and PubMed databases using the terms "gestational diabetes mellitus," "overt diabetes mellitus," and "insulin resistance." In the literature, only full-text articles were considered for inclusion (237 articles). Furthermore, articles published before 1997 and duplicate articles were excluded. After a final review by two experts, all studies (1997-2023) included in the review met the search terms and search strategy (identification from the database, screening of the studies, selection of potential articles, and final inclusion).

Results: Finally, a total of 79 articles were collected for review. Reported risk factors for GDM included maternal obesity or overweight, pre-existing DM, and polycystic ovary syndrome. The pathophysiology of GDM involves genetic variants responsible for insulin secretion and glycemic control, pancreatic β cell depletion or dysfunction, aggravated insulin resistance due to failure in the plasma membrane translocation of glucose transporter 4, and the effects of chronic, low-grade inflammation. Currently, many antepartum measurements including adipokines (leptin), body mass ratio (waist circumference and waist-to-hip ratio], and biomarkers (microRNA in extracellular vesicles) have been studied and confirmed to be useful markers for predicting GDM. For preventing GDM, physical activity and dietary approaches are effective interventions to control body weight, improve glycemic control, and reduce insulin resistance.

Conclusion: This review explored the possible factors that influence GDM and the underlying molecular and cellular mechanisms of GDM and provided predictive measures and prevention strategies based on results of clinical studies.