Systematic Reviews
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2023; 14(11): 1693-1709
Published online Nov 15, 2023. doi: 10.4239/wjd.v14.i11.1693
Cellular and molecular overview of gestational diabetes mellitus: Is it predictable and preventable?
Pei-Qi Lim, Yen-Ju Lai, Pei-Ying Ling, Kuo-Hu Chen
Pei-Qi Lim, Yen-Ju Lai, Pei-Ying Ling, Department of Obstetrics and Gynecology, Taiwan Adventist Hospital, Taipei 105, Taiwan
Pei-Ying Ling, School of Medicine, George Washington University, Washington, DC 20052, United States
Kuo-Hu Chen, Department of Obstetrics and Gynecology, Taipei Tzu-Chi General Hospital, Taipei 231, Taiwan
Kuo-Hu Chen, School of Medicine, Tzu-Chi University, Hualien 970, Taiwan
Author contributions: Lim PQ and Chen KH designed the research study; Lim PQ, Lai YJ, Ling PY, and Chen KH performed the research; Lim PQ, Lai YJ, and Chen KH analyzed the data; Lim PQ, Lai YJ, and Chen KH wrote the manuscript; All authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare having no conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Kuo-Hu Chen, MD, MSc, PhD, Academic Editor, Attending Doctor, Chief Physician, Director, Professor, Senior Editor, Senior Researcher, Surgical Oncologist, Teacher, Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, No. 289 Jianguo Road, 231 Xindian, Taipei 231, Taiwan. alexgfctw@yahoo.com.tw
Received: February 26, 2023
Peer-review started: February 26, 2023
First decision: April 20, 2023
Revised: May 18, 2023
Accepted: October 11, 2023
Article in press: October 11, 2023
Published online: November 15, 2023
Abstract
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.

Keywords: Gestational diabetes mellitus, Overt diabetes mellitus, Insulin resistance, Diabetes mellitus

Core Tip: Maternal and fetal effects of uncontrolled gestational diabetes mellitus (GDM) include stillbirth, macrosomia, neonatal diabetes, and birth trauma. Risk factors are maternal obesity or overweight, pre-existing diabetes mellitus, and polycystic ovary syndrome. The complex pathophysiology involves genetic variants, pancreatic β cell depletion or dysfunction, aggravated insulin resistance due to glucose transporter 4 translocation failure, and chronic, low-grade inflammation. Antepartum measurements including adipokines (leptin), body mass ratio (waist circumference and waist-to-hip ratio), and biomarkers (microRNA in extracellular vesicles) are useful markers for predicting GDM. For preventing GDM, physical activity and diet (such as the Mediterranean diet) control are effective interventions.