The findings of this study indicate a significant association between OBS and the risk of GDM. Since women with GDM were significantly older and had higher BMI than controls, we adjusted for these variables (age and BMI), as well as total calorie intake, in our multivariable logistic regression analyses to reduce potential confounding. The protective associations between higher OBS and reduced GDM risk remained significant after these adjustments, suggesting that the observed relationships were independent of these differences. Women diagnosed with GDM had lower total OBS and dietary OBS compared to the control group. Furthermore, our results demonstrate that higher OBS, particularly in its dietary and lifestyle components, is associated with a lower risk of GDM. Specifically, women in the highest tertile of total OBS had a 23% lower likelihood of developing GDM compared to those in the lowest tertile (adjusted OR = 0.77; 95% CI: 0.48–0.92). Higher dietary OBS also showed a protective association (adjusted OR = 0.81; 95% CI: 0.52–0.98). Notably, lifestyle OBS had the strongest inverse association, with adjusted ORs of 0.66 (95% CI: 0.52–0.92) for the second tertile and 0.52 (95% CI: 0.34–0.78) for the third tertile. These quantitative findings highlight the practical significance of oxidative balance in relation to GDM risk. Additionally, the lower intake of key micronutrients such as riboflavin, folate, magnesium, and zinc in the GDM group highlights the potential role of these nutrients in glucose metabolism and oxidative stress regulation. Conversely, lifestyle OBS was significantly higher in the GDM group, which may be attributed to the higher BMI and lower physical activity levels observed in these participants. It should be noted that although the GDM group exhibited a higher lifestyle OBS, this increase primarily reflects greater pro-oxidant exposure driven by higher BMI and lower physical activity levels. According to the scoring method used in this study, these factors contribute to a higher lifestyle OBS, indicating a greater oxidative burden rather than a protective effect. This explains why lifestyle OBS shows a different direction compared to total and dietary OBS: in our scoring system, higher scores in lifestyle OBS can reflect higher exposure to pro-oxidant lifestyle factors rather than antioxidant benefits. Thus, although higher total and dietary OBS indicate better antioxidant status and lower GDM risk, a higher lifestyle OBS in this context reflects greater oxidative burden and increased GDM risk. We have clarified this distinction to help readers interpret the findings accurately.
Our findings indicate that older maternal age is associated with a higher prevalence of GDM. This aligns with a meta-analysis by Li et al., which included over 120 million participants and demonstrated that GDM risk increases linearly with advancing maternal age [21]. Similarly, Schummers et al. reported a consistent rise in GDM prevalence with maternal age [22]. Although the precise mechanisms remain unclear, elevated insulin resistance, higher circulating adipokines, and increased oxidative stress with age have been proposed as contributing factors [23, 24]. However, a study conducted in mainland China observed that GDM prevalence peaked in women aged 30–34 years and then declined among women older than 35 years [25]. Possible explanations for these differing results include variations in study design (e.g., retrospective vs. prospective), population characteristics such as ethnic composition and baseline metabolic risk, healthcare access and screening strategies, or cultural and behavioral factors affecting older pregnant women (e.g., differences in parity or pre-pregnancy BMI). Recognizing these inconsistencies highlights the complex interplay of biological, environmental, and sociodemographic factors that influence GDM risk and underscores the need for further context-specific research.
Additionally, our results also revealed that BMI was higher in women with GDM. In line with our findings, Chu et al. reported that higher maternal weight is associated with an increased risk of GDM [26]. Similarly, a meta-analysis found that higher pregnancy BMI is significantly linked to GDM prevalence [27]. The proposed mechanisms suggest that obesity causes major changes in maternal intermediary metabolism, with insulin resistance playing a central role. Insulin receptor and post-receptor defects associated with obesity may be further exacerbated by pregnancy [28]. Additionally, inflammation is another possible explanation for the link between obesity and GDM. Although the exact mechanisms underlying GDM development are not fully understood, systemic inflammation appears to be a key factor, as evidenced by elevated serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and ferritin in obese women [29,30,31]. Adipocytes secrete proinflammatory cytokines, and inflammation is commonly associated with obesity. Therefore, an excess of adipocytes in obese women could lead to increased inflammatory marker production, contributing to GDM development.
Our findings add to a growing body of evidence highlighting the potential role of oxidative balance in metabolic health during pregnancy. Specifically, the observed inverse association between total and dietary OBS and GDM risk suggests that greater exposure to antioxidants relative to pro-oxidants may help mitigate oxidative stress–related pathways implicated in glucose intolerance. Prior studies, such as those by Martinez et al. and others, have reported elevated oxidative stress markers in women with GDM, supporting the biological plausibility of our findings [11, 12]. Other research has linked OBS to the development of diabetes and obesity, reinforcing the role of oxidative stress in metabolic disorders [32]. By applying an integrated OBS approach that includes both dietary and lifestyle components, our study complements earlier research focused solely on biochemical markers or individual nutrients. This broader perspective underscores the importance of overall antioxidant capacity and lifestyle factors in the context of GDM risk, rather than isolated exposures alone.
Oxidative damage, resulting from an imbalance between the formation and neutralization of reactive oxygen species (ROS), is associated with membrane lipid destruction and lipid peroxidation [11]. Antioxidants, including enzymatic and non-enzymatic agents, mitigate oxidative stress through natural defense mechanisms [33]. Dietary antioxidants from fruits and vegetables also play a crucial role in neutralizing free radicals. Total antioxidant capacity (TAC) reflects the balance between antioxidants and oxidants, with key antioxidants such as catalase, superoxide dismutase, beta-carotene, vitamins C and E, zinc, magnesium, and glutathione peroxidase (GPX) providing protection against ROS-induced damage [34]. Several studies have reported increased lipid peroxidation and significant reductions in antioxidant capacity during GDM development [35].
Biomarkers of oxidative stress indicate impairments in antioxidant enzymes and non-enzymatic networks, leading to imbalances in oxidant production and detoxification. These biomarkers include oxidized DNA, malondialdehyde (MDA), oxidized low-density lipoprotein (LDL), glutathione, advanced glycation end products, nitrotyrosine, protein carbonyls, and F2-isoprostanes. Many of these oxidative stress markers have been associated with pregnancy complications, including GDM [36].
Regarding micronutrient intake, our findings indicate that riboflavin (B2), folate (B9), magnesium, and zinc were lower in women with GDM. In a study by Mohammad-Parast et al., lower zinc intake was significantly associated with GDM [37]. Another study found a negative association between zinc intake and gestational hyperglycemia [38]. Zinc may mitigate oxidative damage by preventing vitamin E depletion, stabilizing membrane structures, limiting endogenous free radical production, contributing to antioxidant enzyme function, and maintaining metallothionein concentrations as a potential free radical scavenger. Additionally, mild zinc deficiency in animal models has been linked to elevated ceruloplasmin, an acute-phase protein associated with increased free radical production and inflammation [39].
Regarding magnesium intake, recent studies have demonstrated that magnesium supplementation improves insulin sensitivity and reduces oxidative stress in GDM patients [40]. Dietary intervention during pregnancy is considered both a preventive and protective strategy against adverse maternal outcomes. Dysregulated insulin signaling in GDM leads to hyperglycemia, which, in turn, increases inflammation, oxidative stress, and hyperlipidemia. Elevated proinflammatory cytokines and oxidative markers, such as MDA, have been associated with an imbalance between pro-oxidant and antioxidant systems in GDM patients [41].
Consistent with our results, Ge et al. found that higher B2 intake during pregnancy is associated with a lower incidence of GDM [42]. Animal studies suggest that B2 intake may reduce type 2 diabetes risk by decreasing oxidative stress [43]. Riboflavin enhances glucose metabolism through its antioxidant properties, potentially interacting with other nutrients implicated in type 2 diabetes pathogenesis, such as iron and folic acid [44].
Regarding folate (B9) intake, Chen et al. found that B9 supplementation may serve as a protective factor against GDM risk [45]. The Nurses’ Health Study II reported that preconception B9 supplementation is inversely associated with GDM risk [46]. Potential mechanisms include the role of folate in modulating insulin resistance, methylation processes, and phosphatidylcholine synthesis. Animal studies have demonstrated that inadequate folate intake may impair insulin sensitivity through compromised methylation and altered lipid metabolism [47]. Moreover, folic acid supplementation may upregulate AMP-activated protein kinase (AMPK), thereby improving insulin resistance in high-fat diet-induced models [48]. Another proposed mechanism involves the reduction of homocysteine levels, which have been linked to insulin resistance, oxidative stress, and systemic inflammation factors that interfere with insulin function.
Finally, physical activity plays a crucial role in GDM prevention. Studies indicate that regular physical activity during pregnancy can be safely performed and effectively prevents excessive weight gain and GDM development [49]. Additionally, exercise has been identified as a preventive strategy for GDM and is recommended as a key lifestyle intervention for at-risk pregnant women [50]. Taken together, our findings reinforce the importance of both diet quality and lifestyle modifications in reducing GDM risk. However, more evidence is needed to fully understand the impact of such interventions on maternal and neonatal outcomes and to clarify the underlying mechanisms involved.
Strengths and limitations
This study has several notable strengths. First, it provides a comprehensive examination of the relationship between the OBS and the risk of GDM, offering valuable insights into the role of oxidative stress in GDM pathogenesis. The inclusion of both dietary and lifestyle components in the OBS allows for a holistic assessment of pro-oxidant and antioxidant exposures, which is a significant advancement over studies focusing solely on individual nutrients or lifestyle factors. Additionally, the use of a validated FFQ and the application of PCA to identify dietary patterns enhance the robustness of the dietary assessment. The study’s case-control design, with careful matching of participants and adjustment for potential confounders, strengthens the validity of the observed associations. Furthermore, the findings align with existing literature, reinforcing the importance of oxidative stress and micronutrient intake in GDM risk, and provide a foundation for future research and clinical recommendations.
However, the study also has limitations. The case-control design, while useful for identifying associations, cannot establish causality, and the possibility of recall bias in self-reported dietary and lifestyle data cannot be ruled out. The study population was limited to women in Urmia, Iran, which may restrict the generalizability of the findings to other populations with different dietary habits, genetic backgrounds, or healthcare systems. Finally, while the study highlights the importance of oxidative stress and micronutrients, it does not explore the potential interactions between different dietary components or the mechanisms underlying their effects on GDM risk in detail.
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