Correlation between serum advanced glycation end-products and their receptor-mediated oxidative stress and perinatal outcomes in gestational diabetes mellitus

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

Figure 1

Flow diagram of the patient selection. GDM: Gestational diabetes mellitus; DM: Diabetes mellitus; BMI: Body mass index; AGE: Advanced glycation end-product; sRAGE: Soluble advanced glycation end-product receptor; RAGE: Advanced glycation end-product receptor.

Figure 2

Receptors for soluble advanced glycation end-product protein expression in placental tissues of pregnant women in the two groups. GDM: Gestational diabetes mellitus; sRAGE: Soluble advanced glycation end-product receptor; ^aP < 0.001.

Figure 3

Correlation of serum indicators in pregnant women in the gestational diabetes mellitus group. A: Correlation between serum advanced glycation end-products (AGEs) and soluble AGE receptor levels at 24-28 weeks of gestation and before delivery; B: Correlation between serum AGEs and superoxide dismutase levels at 24-28 weeks of gestation and before delivery; C: Correlation between serum AGEs and malondialdehyde levels at 24-28 weeks of gestation and before delivery. sRAGE: Soluble advanced glycation end-product receptor; SOD: Superoxide dismutase; MDA: Malondialdehyde; AGEs: Advanced glycation end-products.