Serum Oxidative Stress Biomarkers and Antioxidant Enzyme Activity as Predictors of Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus

Background: Cardiovascular disease (CVD) continues to be the leading contributor to illness and death in people with type 2 diabetes mellitus (T2DM). Oxidative stress has been recognized as a central factor in vascular damage, but its usefulness as a predictive marker through measurable biochemical indicators and antioxidant enzyme activity remains underexplored in South Asian populations. Objective: This study aimed to investigate the link between cardiovascular risk and circulating oxidative stress biomarkers together with antioxidant enzyme activity in patients with T2DM. Methods: A cross-sectional analysis was undertaken in three tertiary care hospitals in Lahore, Pakistan, from March 2023 to January 2025. A total of 120 adults with T2DM, aged 35–70 years and living with the disease for at least five years, were included. The Framingham Risk Score was used to assess cardiovascular risk, and individuals were classified as either high risk or low–moderate risk. Serum malondialdehyde (MDA), protein carbonyls (PC), and advanced oxidation protein products (AOAPs) were used to quantify the oxidative stress. The levels of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) were measured to assess the antioxidant defense. Additional investigations were also out, including lipid profiles, glycated hemoglobin (HbA1c), and high-sensitivity C-reactive protein. Results: Out of the total participants, 52 (43.3%) were classified as high risk. Individuals had substantially greater levels of MDA (5.4 ± 1.1 vs. 3.2 ± 0.7 nmol/mL; p < 0.001), PC (2.6 ± 0.5 vs. 1.8 ± 0.4 nmol/mg; p = 0.002), and AOPPs (92.1 ± 15.6 vs. 68.4 ± 12.3 µmol/L; p < 0.001). The high-risk group had substantially reduced antioxidant enzyme activity for SOD (5.1 ± 1.0 vs. 7.2 ± 1.3 U/mL; p < 0.001), CAT (33.8 ± 5.9 vs. 42.5 ± 6.2 kU/L; p < 0.01), and GPx (49.5 ± 7.2 vs. 62.7 ± 8.4 U/mL; p < 0.01). Regression analysis showed that elevated cardiovascular risk was independently predicted by higher MDA (OR 2.9, 95% CI 1.8-4.5; p < 0.001) and decreased SOD activity (OR 2.3, 95% CI 1.4-3.9; p = 0.002). Conclusion: Patients with T2DM who are at greater cardiovascular risk display higher oxidative stress and reduced antioxidant enzyme defense. The inclusion of these biomarkers in clinical evaluation may refine cardiovascular risk prediction and guide targeted preventive measures.