Retrospective Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 15, 2025; 16(6): 104177
Published online Jun 15, 2025. doi: 10.4239/wjd.v16.i6.104177
Correlation between serum advanced glycation end-products and their receptor-mediated oxidative stress and perinatal outcomes in gestational diabetes mellitus
Ying Zhang, Teng Li, Zhi-Heng Wang, Yun Liu
Ying Zhang, Zhi-Heng Wang, Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
Teng Li, Department of Interventional Radiology, The People’s Hospital of Weifang City, Weifang 261041, Shandong Province, China
Yun Liu, Department of Hematology, The People’s Hospital of Weifang City, Weifang 261041, Shandong Province, China
Author contributions: Zhang Y designed the research and wrote the manuscript draft; Zhang Y, Li T, Wang ZH, and Liu Y contributed to conceptualization and data analysis; Zhang Y and Liu Y conducted analysis and provided guidance for the research; all authors reviewed and approved the final manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Obstetrics and Gynecology Hospital of Fudan University.
Informed consent statement: All study participants or their legal guardian provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There is no conflict of interest.
Data sharing statement: No additional data are available.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yun Liu, Department of Hematology, The People’s Hospital of Weifang City, No. 151 Guangwen Street, Kuiwen District, Weifang 261041, Shandong Province, China. yun.1100@163.com
Received: January 8, 2025
Revised: March 17, 2025
Accepted: May 7, 2025
Published online: June 15, 2025
Processing time: 156 Days and 4.2 Hours
Abstract
BACKGROUND

Gestational diabetes mellitus (GDM) is one of the most prevalent metabolic disorders of pregnancy. Advanced glycation end-products (AGEs) are a complex and highly heterogeneous group of compounds formed from amino acids and reducing sugars. High-AGE diet exposure during pregnancy may cause adverse effects.

AIM

To investigate the expression levels of AGE and AGE receptor (RAGE) in the serum and placenta of pregnant women with GDM and to assess the association of their mediated oxidative stress response with perinatal outcomes.

METHODS

This study retrospectively analyzed the clinical data of 126 pregnant women with GDM who gave birth in the Obstetrics Department of Obstetrics and Gynecology Hospital of Fudan University from January 2023 to January 2024. A total of 85 pregnant women of similar age without GDM during the same period were selected as the control group. Fasting blood glucose, glycated hemoglobin, AGEs, soluble RAGE (sRAGE), and oxidative stress were compared in both groups. Postpartum placental tissue was collected to identify RAGE protein expression. Participants with GDM were categorized based on perinatal outcomes into normal (n = 89) and adverse perinatal outcome groups (n = 37), and differences in serum AGE–RAGE levels and oxidative stress were analyzed. The influencing factors of adverse perinatal outcomes were analyzed using logistic regression.

RESULTS

The GDM group demonstrated notably higher serum AGE (t = 8.955) and malondialdehyde (MDA) levels (t = 14.14) and lower sRAGE (t = 16.37) and superoxide dismutase (SOD) levels (t = 18.50) than the control group at 24-28 weeks of gestation and before delivery (P < 0.0001). Serum AGE levels were positively correlated with MDA and negatively related to SOD at 24-28 weeks of pregnancy (SOD: r = 0.393, MDA: r = 0.424, P < 0.0001) and before delivery (SOD: r = 0.443, MDA: r = 0.492, P < 0.0001), whereas AGE was inversely associated with sRAGE in the GDM group (r = -0.495, P < 0.0001). Serum AGE levels were significantly higher (t = 9.225, P < 0.0001) and the sRAGE level (r = 3.563, P < 0.0001) was significantly lower in participants with adverse perinatal outcomes than those with normal perinatal outcomes in the GDM group. Logistic regression analysis revealed AGE level as a risk factor (OR = 1.056, P < 0.0001) and sRAGE level (OR = 0.949, P < 0.0001) as a protective factor for adverse perinatal outcomes in GDM.

CONCLUSION

High serum AGE level is a risk factor for adverse perinatal outcomes in GDM, whereas high sRAGE levels are protective. AGEs and RAGE may be associated with oxidative stress in pregnant women with GDM.

Keywords: Gestational diabetes mellitus; Advanced glycation end-products; Hemoglobin; Fasting blood glucose; Perinatal outcomes

Core Tip: Advanced glycation end-products (AGEs) are a complex and highly heterogeneous group of compounds formed from amino acids and reducing sugars, primarily produced during thermal and metabolic processing of food. To date, a few studies have demonstrated the role of AGEs in gestational diabetes mellitus (GDM) pathophysiology. Therefore, in this study, we aimed to understand the association of AGEs with oxidative stress in GDM. We found that serum AGE levels were significantly correlated with patient oxidative stress status at 24-28 weeks of pregnancy and before delivery. Meanwhile, AGE level was a risk factor, and its receptor soluble receptor AGE level was a protective factor for adverse perinatal outcomes in GDM.