Naghma Abdulsahib Hussein (1)
General Background: Spontaneous abortion is a common pregnancy complication with higher occurrence among women with diabetes mellitus, where oxidative imbalance and micronutrient deficiency are implicated. Specific Background: Oxidative stress markers such as malondialdehyde (MDA) and antioxidant enzymes like superoxide dismutase (SOD), together with vitamin D₃ status and glycemic indices, are associated with adverse pregnancy outcomes. Knowledge Gap: However, the interrelationship between oxidative stress, antioxidant defense, glycemic control, and vitamin D₃ levels in diabetic women experiencing miscarriage remains insufficiently characterized. Aims: This study assessed MDA and SOD levels and their association with glycemic parameters and vitamin D₃ in diabetic women with spontaneous abortion. Results: A case–control analysis of 80 women revealed significantly higher random blood sugar, HbA1c, and MDA levels, alongside significantly lower vitamin D₃ levels in patients compared to controls (p < 0.001). SOD activity was significantly altered, indicating disrupted antioxidant defense. HbA1c showed strong positive correlation with MDA (r = 0.847) and negative correlations with SOD (r = −0.748) and vitamin D₃ (r = −0.702). Novelty: This study demonstrates integrated correlations between oxidative stress biomarkers, antioxidant imbalance, glycemic dysregulation, and vitamin D₃ deficiency in diabetes-related miscarriage. Implications: These findings suggest that combined monitoring of oxidative stress markers, glycemic indices, and vitamin D₃ status may support improved understanding and management of miscarriage risk in diabetic women.
Highlights:• Elevated lipid peroxidation and glucose indicators observed in affected patients• Reduced micronutrient status linked with altered antioxidant enzyme activity• Strong correlations identified among metabolic, oxidative, and nutritional parameters
Keywords: Oxidative Stress, Malondialdehyde, Superoxide Dismutase, Diabetes Mellitus, Vitamin D3
An abortion that ends before 20 weeks of gestation is referred to as a "spontaneous abortion" and happens between 10% and 15% of the time [1]. Due to the fact that many abortions take place prior to pregnancy being clinically recognized, the actual incidence is unknown [2]. Spontaneous abortion arises out of an imbalance of the formation of reactive oxygen species (ROS) and antioxidant safeguarding [3]. Despite the overexpression of antioxidants such as catalase, glutathione peroxidase, Cu/Zn, and Mn superoxide dismutase, placental tissue from early pregnancy losses showed an increase in oxidative stress indicators, such as MDA and lipid peroxides, compared with controls [4]. The most frequent ROS under physiological settings are superoxide anions (SOA) [5]. They are created when molecular oxygen receives an additional electron. In plasma, whole blood, and/or placental tissue of Recurrent Miscarriages (RM) patients, recent investigations have shown considerably lower activity levels of both enzymatic and non-enzymatic antioxidants, including glutathione peroxidase, catalase, glutathione reductase, reduced glutathione, and selenium [6],[7]. Nevertheless, when ROS generation exceeds what is often seen in cells, uncontrolled attack on cellular organelles and shifts to the structure of macromolecules, including proteins, nuclear and mitochondrial DNA, and membrane lipids arise [8],[9].
Gestational diabetes (GD) and pre-eclampsia (PE) are serious pregnancy problems with clinical and social consequences. After 20 weeks of gestation, pre-eclampsia causes new-onset hypertension, proteinuria, and systemic organ failure in 2–15% of pregnancies [10]. This disease can cause fetal growth limitation, preterm birth, and maternal morbidity. Although placental oxidative stress is thought to cause PE, its molecular mechanisms are unknown [11]. PE has high levels of oxidized lipids and proteins, suggesting that placental oxidative stress overwhelms antioxidant defenses and causes systemic inflammation and endothelial dysfunction [12]. Oxidative imbalance may impede insulin signaling, linking PE to gestational diabetes. Macrosomia, stillbirth, and newborn hypoglycemia increase with gestational diabetes [13].
Oxidative stress, including elevated levels of Malondialdehyde (MDA), a consequence of lipid peroxidation, and diminished antioxidant defenses including vitamin C, E, zinc, and antioxidant enzymes, is connected to abortion, especially spontaneous miscarriage. Studies have linked oxidative damage to miscarriage, with higher MDA levels associated with recurrent miscarriages and possibly older maternal age. Results vary by type of abortion (threatened, incomplete) and stage [14].[15].
A case-control research collected 80 women samples, 40 controls and 40 abortion with diabetes women. A delegation visited Shaheed mohammed baqir Al- hakim hospital Teaching Hospitals examined patients from October 12024 to February 10, 2025.
The study included women aged 18–40 with a history of recurrent spontaneous abortion and diabetes mellitus, verified by FBG,HBA1C. Women with genetic abnormalities, SLE, acute or chronic infections, smoking, or alcohol intake were excluded. Take blood samples for MDA, SOD, D3, and glucose profiles (FBS, HBA1C). Both patients and controls gave 5 ml of blood. Measure HBA1C in 2 ml EDTA tube within 30 minutes. A gel tube held 3 ml of blood for 30 minutes to coagulate. The serum was obtained by centrifuging vials at 3000 RPM for 15 minutes. Isolated serum is stored at -20°C until needed. ELISA was recommended by Sunlog to measure SOD,MAD, and D3. The Bodytech, S. Korea, operational manual describes the HBA1C test using the AFIAS-6 instrument and fluorescence immunoassay (FIA). FBS is done using a spectrophotometer and colorimetric technique, per the BIOLABO, France, operational manual.
The control group had a mean age of 28.89 ± 6.41 years, while the sick group had a mean age of 27.36 ± 8.68 years, with no significant difference (p = 0.071). BMI was similar between controls (25.66 ± 4.04 kg/m²) and patients (25.11 ± 3.09 kg/m²) (p = 0.358), indicating similar age and BMI. Patients had considerably higher RBS levels (241.26 ± 50.07 mg/dL) compared to controls (105.58 ± 10.74 mg/dL) (p < 0.001). HbA1c values were significantly higher in the patient group (7.97 ± 1.03%) compared to the control group (5.08 ± 0.63%) (p < 0.001), indicating inadequate glycemic management in diabetic aborted patients. Patients had considerably lower serum vitamin D3 levels (13.65 ± 3.98 ng/mL) compared to healthy controls (36.91 ± 14.02 ng/mL) (p < 0.001), indicating a serious vitamin D insufficiency. Patients had higher levels of malondialdehyde (MDA), a measure of lipid peroxidation and oxidative stress (119.09 ± 23.41) compared to controls (38.30 ± 7.21) (p < 0.001). Additionally, a substantial difference in Superoxide Dismutase (SOD) activity between diabetic women with abortion (98.37 ± 44.07) and controls (31.69 ± 71.47) (p < 0.001) indicates an imbalance in antioxidant defense systems.
Table 1. Comparison of Demographic, Glycemic, Oxidative Stress, and Antioxidant Parameters Between Diabetic Aborted Patients and Healthy Controls
Pearson correlation analysis showed significant associations between glycemic parameters, oxidative stress markers, antioxidant status, and vitamin D3 levels in the studied groups. HbA1c correlated positively with MDA (r = 0.847, p < 0.01) and RBS (r = 0.883, p < 0.01), linking poor glycemic management to raised oxidative stress and blood glucose levels. HbA1c was inversely linked with SOD (r = -0.748, p < 0.01) and vitamin D3 (r = -0.702, p < 0.01), indicating decreased antioxidant defense and vitamin D status with deteriorating glycemic control.
MDA showed a substantial negative correlation with SOD (r = -0.835, p < 0.01) and vitamin D3 (r = -0.730, p < 0.01), whereas a positive correlation with RBS (r = 0.873, p < 0.01). Increased oxidative stress is linked to hyperglycemia and impaired antioxidant activity.
SOD correlated positively with vitamin D3 (r = 0.768, p < 0.01) and negatively with RBS (r = −0.762, p < 0.01), indicating antioxidant enzymes and vitamin D protect against oxidative stress and hyperglycemia.
Hyperglycemia, oxidative stress, antioxidant capacity, and vitamin D3 levels were strongly correlated in women with diabetes-related miscarriage compared to healthy controls at the 0.01 level.
Table 2 Correlation Analysis Between Glycemic Indices, Oxidative Stress Markers, and Vitamin D3 Levels in Women with Diabetes-Related Miscarriage and Healthy Controls
The present study compared demographics, glycemic management, vitamin D status, oxidative stress, and antioxidant defense in diabetic women with abortion to healthy controls. Poor glycemic management, increased oxidative stress, and vitamin D deficiency may cause miscarriage in diabetics. Patients and controls were demographically similar in this study, with no significant variations in age or BMI. This reduces the confounding effects of age and body composition on metabolic markers and strengthens the diabetes-abortion connections [16].
The patient group had significantly higher RBS and HbA1c than controls. High HbA1c indicates persistent hyperglycemia, which impairs placental function, increases inflammation, and damages endothelium. Poor glycemic control in early pregnancy is highly associated with spontaneous abortion and unfavorable pregnancy outcomes, indicating hyperglycemia as a major cause of diabetic pregnancy loss [17].
In diabetic aborted patients, blood vitamin D3 levels dropped significantly. Vitamin D helps regulate pregnancy's immune system, placental development, and inflammatory reactions. Vitamin D deficiency may worsen hyperglycemia by causing insulin resistance and glucose metabolism issues. Inadequate vitamin D levels may increase miscarriage risk by dysregulating maternal–fetal immune tolerance [18].
The patient group had elevated malondialdehyde (MDA) levels, indicating oxidative stress. Hyperglycemia causes ROS overproduction, lipid peroxidation, cellular damage, and placental failure. Diabetics' high MDA levels are linked to pregnancy problems, including termination [19].
SOD activity was considerably changed in patients compared to controls. This may indicate a compensatory increase of antioxidant enzymes in response to severe oxidative stress or a failing antioxidant defense mechanism [20].
Agreement with the present study multiple studies have connected diabetes-related spontaneous abortion to poor glycemic control, as defined by high HbA1c and blood glucose. According to Mills et al. chronic hyperglycemia during early pregnancy increases miscarriage risk due to poor placental development and embryonic abnormalities [21]. Vitamin D deficiency is more common in diabetic women and connected to insulin resistance, immunological dysregulation, and pregnancy loss, according to Bodnar et al. [22]. Aborted diabetics have decreased vitamin D3 levels. Vitamin D insufficiency may lower maternal immune tolerance, which is important for pregnancy. Patients' elevated MDA levels support Ceriello and Motz, and Maritim et al., who demonstrated that hyperglycemia enhances reactive oxygen species generation, causing lipid peroxidation and cellular damage. High MDA levels often cause diabetes and pregnancy difficulties. Diabetes patients have increased or dysregulated antioxidant enzyme activity, particularly SOD, to compensate for oxidative stress, according to Al-Azzawie and Alhamdani [23][24][25].
Significant connections were found between glycemic indices, oxidative stress indicators, antioxidant status, and vitamin D3 levels in diabetes-related miscarriage and healthy controls. Bad glycemic management (high HbA1c and random blood sugar) was connected to oxidative stress and reduced antioxidant defense. The strong positive correlation between HbA1c and MDA suggests chronic hyperglycemia enhances lipid peroxidation and oxidative damage. This suggests that high glucose levels produce reactive oxygen species (ROS) that disrupt placental function and cause miscarriage [26].
Conversely, the strong negative correlation between HbA1c and SOD shows that poor glycemic management lowers antioxidant enzyme activity. During pregnancy, SOD deficiency may impair cellular defenses against oxidative stress, increasing tissue damage risk. Due to the inverse relationship between HbA1c and vitamin D3, vitamin D deficiency may aggravate metabolic dysregulation and oxidative stress in diabetic women [27].
MDA interacted negatively with SOD and vitamin D3, suggesting oxidative stress reduces antioxidant capacity and vitamin D. Vitamin D3 deficiency may increase oxidative damage in miscarrying women due to its antioxidant and anti-inflammatory properties. The positive link between RBS and MDA and the negative correlation between RBS and SOD reveal that hyperglycemia immediately affects oxidative stress imbalance. The high positive correlation between SOD and vitamin D3 shows vitamin D may increase antioxidant defenses [28].
These findings imply that hyperglycemia-induced oxidative stress, antioxidant inactivity, and vitamin D deficiency may cause diabetes miscarriage. Glycemic control, oxidative stress reduction, and vitamin D supplementation may improve pregnancy outcomes in this vulnerable population.
The studies supporting this study Ceriello A., et al., this study found that prolonged hyperglycemia increases lipid peroxidation and decreases antioxidant enzyme activity, specifically superoxide dismutase [29]. Oxidative stress exacerbates diabetes, especially during pregnancy, according to the scientists. And Parildar H., et al., Vitamin D levels shown a negative correlation with indices of oxidative stress in individuals with diabetes [30]. Elevated vitamin D levels enhanced antioxidant status and glycemic regulation. While disagreement this study Muscogiuri G., et al., [31]. In contrast, this study identified no significant association between vitamin D levels and glycemic control markers such HbA1c, suggesting that non-metabolic variables may affect vitamin D deficiency.
This study demonstrates that spontaneous abortion in diabetic women is strongly associated with poor glycemic control, increased oxidative stress, disrupted antioxidant defense, and significant vitamin D₃ deficiency. Elevated malondialdehyde levels reflect enhanced lipid peroxidation induced by chronic hyperglycemia, while altered superoxide dismutase activity indicates an imbalance in antioxidant protection. The observed correlations between glycemic indices, oxidative stress markers, and vitamin D3 emphasize their interconnected role in pregnancy loss among diabetic women. Effective glycemic management, reduction of oxidative stress, and correction of vitamin D deficiency may be essential strategies to improve pregnancy outcomes and reduce miscarriage risk in this vulnerable population.
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