Serum Oxidative Stress Biomarkers and Antioxidant Enzyme Activity as Predictors of Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus
Antioxidant Enzyme Activity and Heart Risk in Diabetes
DOI:
https://doi.org/10.69750/dmls.02.07.0137Keywords:
Type 2 diabetes, cardiovascular risk, oxidative stress, biomarkers, antioxidant defenceAbstract
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.
Downloads
References
Ryan S. Mechanisms of cardiovascular disease in obstructive sleep apnea. J Thorac Dis. 2018;10(Suppl 1):S29–45. doi:10.21037/jtd.2017.10.03
Tietjens JR, Claman D, Kezirian EJ, et al. Obstructive sleep apnea in cardiovascular disease: a review of the literature and proposed multidisciplinary clinical management. J Am Heart Assoc. 2019;8(6):e010440. doi:10.1161/JAHA.118.010440
Labarca G, Dreyse J, Drake L, et al. Hypoxemic burden in obstructive sleep apnea: clinical usefulness beyond the apnea–hypopnea index. Sleep Breath. 2021;25(1):95–103. doi:10.1007/s11325-020-02064-7
Yeghiazarians Y, Jneid H, Tamis-Holland JE, et al. Obstructive sleep apnea and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2021;143(25):e711–30. doi:10.1161/CIR.0000000000000988
Javaheri S, Barbé F, Campos-Rodriguez F, et al. Interactions of obstructive sleep apnea with cardiovascular physiology: clinical implications. J Am Coll Cardiol. 2024;83(8):1124–34. doi:10.1016/j.jacc.2024.02.059
DiCaro MV, Kanaan AO, Fernandez C, et al. Effects of obstructive sleep apnea on the cardiovascular system: mechanisms and implications. J Clin Med. 2024;13(11):3223. doi:10.3390/jcm13113223
Albertsen IE, Nissen L, Larsen JM, et al. Cardiovascular risk in young adults diagnosed with obstructive sleep apnea: a nationwide cohort study. J Am Heart Assoc. 2024;13(3):e033506. doi:10.1161/JAHA.123.033506
Grewal N, Yadava M, De Backer W, et al. Impact of obstructive sleep apnea treatment on cardiovascular outcomes: a systematic review and meta-analysis. Lancet Respir Med. 2024;12(5):556–66. doi:10.1016/S2213-2600(23)00556-X
Eulenburg C, Weinreich G, Bitter T, et al. Prevalence of obstructive sleep apnea and cardiovascular outcomes in patients with coronary artery disease. Ann Am Thorac Soc. 2023;20(5):676–85. doi:10.1513/AnnalsATS.202208-676OC
Bushi G, Teshome T, Mekonnen G, et al. Obstructive sleep apnea and cardiovascular disease in diabetic populations: a systematic review and meta-analysis. J Diabetes Complications. 2023;37(5):108432. doi:10.1016/j.jdiacomp.2023.108432
Yasir M, Farooq S, Mahmood S, et al. Cardiovascular outcomes in patients with sleep-disordered breathing: mechanisms and evidence. Front Neurol. 2022;13:801167. doi:10.3389/fneur.2022.801167
Marin JM, Sánchez-de-la-Torre M, Barceló A, et al. Effect of CPAP on cardiovascular events in patients with acute coronary syndrome and obstructive sleep apnea (ISAACC trial). Lancet Respir Med. 2020;8(4):359–67. doi:10.1016/S2213-2600(19)30271-1
Zapater A, Sánchez-de-la-Torre M, Benítez I, et al. Effect of sleep apnea on cardiovascular events in different acute coronary syndrome phenotypes. Am J Respir Crit Care Med. 2020;202(12):1698–706. doi:10.1164/rccm.202004-1127OC
McNicholas WT. Translation of obstructive sleep apnea pathophysiology into clinical phenotypes to tailor treatment. J Thorac Dis. 2023;15(5):2340–50. doi:10.21037/jtd-22-23494
Lv R, Li H, Chen Y, et al. Pathophysiological mechanisms and therapeutic strategies in obstructive sleep apnea syndrome. Signal Transduct Target Ther. 2023;8:9. doi:10.1038/s41392-023-01496-3
Mazzotti DR, Keenan BT, Lim DC, et al. Symptom subtypes of OSA predict incidence of cardiovascular outcomes. Am J Respir Crit Care Med. 2019;200(4):493–506. doi:10.1164/rccm.201808-1509OC
Azarbarzin A, Sands SA, Stone KL, et al. The sleep apnea–specific pulse rate response predicts cardiovascular morbidity and mortality. Am J Respir Crit Care Med. 2023;207(12):1546–55. doi:10.1164/rccm.202303-0524OC
Lisan Q, Van Sloten TT, Marques-Vidal P, et al. PAP prescription and mortality in obese patients with severe obstructive sleep apnea. JAMA Otolaryngol Head Neck Surg. 2019;145(6):509–15. doi:10.1001/jamaoto.2019.0281
McEvoy RD, Antic NA, Heeley E, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. N Engl J Med. 2016;375(10):919–31. doi:10.1056/NEJMoa1606599 (included as foundational trial)
Benjafield AV, Ayas NT, Eastwood PR, et al. Effect of positive airway pressure on cardiovascular outcomes in coronary artery disease patients with nonsleepy OSA. Lancet Respir Med. 2025;13(1):e5. doi:10.1016/S2213-2600(25)00002-5
Mazzotti DR, Keenan BT, Lim DC, et al. Positive airway pressure, mortality, and cardiovascular risk in older patients with OSA. JAMA Netw Open. 2024;7(2):e2823539. doi:10.1001/jamanetworkopen.2024.23539
Aurora RN, Punjabi NM. Obstructive sleep apnea and type 2 diabetes mellitus: pathophysiologic interactions and therapeutic approaches. Chest. 2019;156(1):184–95. doi:10.1016/j.chest.2019.03.033
Javaheri S, Barbé F, Campos-Rodriguez F, et al. Sleep apnea: types, mechanisms, and clinical cardiovascular consequences. J Am Coll Cardiol. 2017;69(7):841–58. doi:10.1016/j.jacc.2016.11.069 (kept for mechanistic foundation)
Ryan S, McNicholas WT. Intermittent hypoxia and activation of inflammatory molecular pathways in OSA. Arch Physiol Biochem. 2019;125(1):1–10. doi:10.1080/13813455.2018.1469680
Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S. Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation. 2017;136(19):1840–50. doi:10.1161/CIRCULATIONAHA.117.029400















