Oxidative Stress and Antioxidant Status in Pregnant Women with Gestational Diabetes Mellitus and Late-Onset Complication of Pre-Eclampsia

Abstract

Oxidative stress is a critical factor in the onset of gestational diabetes and its associated complication, pre-eclampsia. This study aimed to evaluate (1) reactive oxygen species, reactive nitrogen species, and superoxide radical levels as indicators of oxidative stress, (2) lipid and protein oxidation, (3) antioxidant enzyme activity, and (4) cytokine production in pregnant women with gestational diabetes, as well as those with both gestational diabetes and pre-eclampsia, comparing these with biomarkers of gestational diabetes mellitus. The study categorized pregnant patients with gestational diabetes mellitus into two groups based on the presence of new-onset hypertension, measured twice every four hours, and a 24 h urine protein test showing 300 mg/day or ≥1+ proteinuria detected via a visual dipstick at ≥20 weeks of gestation. These groups were compared with normotensive pregnant patients. The findings revealed that patients with both gestational diabetes and pre-eclampsia exhibited significantly elevated levels of reactive oxygen species, cytokine production, and lipid and protein oxidation end products compared to normotensive pregnant women. Additionally, these patients showed reduced nitric oxide (•NO) levels, impaired NO synthase systems (eNOS and iNOS), and decreased antioxidant enzyme activities (p < 0.05). These results indicate that patients with gestational diabetes and pre-eclampsia are unable to counteract oxidative stress effectively. The study underscores the compromised oxidative status as a contributing factor to these complications. The findings provide insights into the pathogenesis of gestational diabetes and the subsequent pre-eclampsia, the role of oxidative stress, and the resulting complications. Measuring oxidative stress levels and inflammatory biomarkers could help in the early detection and prediction of gestational-diabetes-related complications in pregnant women.

Keywords: NO; eNOS; gestational diabetes mellitus; iNOS; oxidative stress; pre-eclampsia.

Figure 1

Shows the levels of oxidative stress markers presented as; levels of advanced glycation end product (AGE) controls, and protein carbonyl (PCC) levels: (A) AGEs: normotensive pregnancy (control); GDM patients; and GDM + PE; and (B) PCC: normotensive pregnancy (control); GDM patients; and GDM + PE; Turkey HSD post hoc test; * p < 0.05 vs. control group;.

Figure 2

Shows the levels of oxidative stress markers presented as ROS production, MDA, and 8-Iso-prostaglandin: (A) ROS production: normotensive pregnancy (control); GDM patients; and GDM + PE; (B) MDA: normotensive pregnancy (control); GDM patients; and GDM + PE; and (C) 8-Iso-prostaglandin: normotensive pregnancy (control); GDM patients; and GDM + PE; Turkey HSD post hoc test; * p < 0.05 vs. control group; ** p < 0.05 vs. GDM + PE group.

Figure 3

Shows the levels of damage in DNA presented as levels of 8-OHdG [pg/mL], measured in groups with the following: normotensive pregnancy (control); GDM patients; and GDM + PE. Turkey HSD post hoc test; * p < 0.05 vs. control group; ** p < 0.05 vs. GDM + PE group.

Figure 4

Shows the evaluation of the levels of oxidative stress markers presented as NO levels, •O_2‾, eNOS, and iNOS in serum samples: (A) NO: normotensive pregnancy (control); GDM patients; and GDM + PE; (B) •O_2‾: normotensive pregnancy (control); GDM patients; and GDM + PE; (C) eNOS: normotensive pregnancy (control); GDM patients; and GDM + PE; and (D) iNOS: normotensive pregnancy (control); GDM patients; and GDM + PE; Turkey HSD post hoc test; * p < 0.05 vs. control group; ** p < 0.05 vs. GDM + PE group.

Figure 5

Pro-inflammatory cytokine levels: (A) IL-1α; (B) IL-1β; (C) IL-6; (D) IL-10; (E) IL-17A; (F) IFN-γ; (G) TNF-α; and (H) TGF-β; Tukey HSD post hoc test; * p < 0.05 vs. control group; ** p < 0.05 vs. GDM + PE group.

Figure 5

Pro-inflammatory cytokine levels: (A) IL-1α; (B) IL-1β; (C) IL-6; (D) IL-10; (E) IL-17A; (F) IFN-γ; (G) TNF-α; and (H) TGF-β; Tukey HSD post hoc test; * p < 0.05 vs. control group; ** p < 0.05 vs. GDM + PE group.