Original Articles

Integrated Oxidative and Cardiac Biomarker Profile in Type 2 Diabetes Mellitus With Acute Coronary Syndrome

Abstract

Type 2 diabetes mellitus (T2DM) substantially increases the risk of acute coronary syndrome (ACS) through the combined effects of chronic hyperglycemia, dyslipidemia, oxidative stress, endothelial dysfunction, and myocardial injury. This study aimed to comprehensively evaluate metabolic, oxidative stress, and cardiac biomarkers in patients with T2DM complicated by ACS, and to investigate their diagnostic performance and interrelationships. A case-control study was conducted including 60 patients with T2DM complicated by ACS and 30 apparently healthy controls. Fasting blood glucose (FBS), glycated hemoglobin (HbA1c), lipid profile, glutathione, lipid peroxidation, superoxide, homocysteine (HCY), Na+/K±ATPase, and cardiac troponin were determined using standard laboratory methods. Compared with healthy controls, patients with T2DM and ACS exhibited significantly elevated FBS, HbA1c, total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), HCY, and lipid peroxidation, whereas high-density lipoprotein cholesterol (HDL-C), glutathione, and Na+/K±ATPase activity were significantly reduced (all P<0.001). Superoxide levels were also significantly decreased in patients compared with healthy controls (P<0.001). Correlation analysis demonstrated a significant positive correlation between cardiac troponin and Na+/K±ATPase activity (r=0.337, P=0.008), while no significant correlations were observed between FBS, HbA1c, lipid profile parameters, oxidative stress biomarkers, HCY, and the remaining investigated biomarkers. ROC analysis demonstrated excellent diagnostic performance for Na+/K±ATPase, glutathione, lipid peroxidation, superoxide, and HCY, with high sensitivity and specificity for discriminating patients from healthy controls. In conclusion, patients with T2DM complicated by ACS exhibit profound metabolic disturbances coupled with pronounced oxidative stress, hyperhomocysteinemia, altered Na+/K±ATPase activity, and myocardial damage, highlighting the utility of integrated biomarker profiling.

1. Davies MJ, Lim S, Slater T, Goldney J, Philis-Tsimikas A, Franco DR, et al. Type 2 diabetes mellitus. Nat Rev Dis Prim 2026;12:13.
2. Pantea Stoian A, Roman G. Cardiovascular Risk/Disease in Type 2 Diabetes Mellitus. In: Pantea Stoian A, editor. Type 2 Diabetes - From Pathophysiology to Cyber Systems. London: IntechOpen; 2021.
3. Strikić D, Vujević A, Perica D, Leskovar D, Paponja K, Pećin I, et al. Importance of Dyslipidaemia Treatment in Individuals with Type 2 Diabetes Mellitus—A Narrative Review. Diabetology 2023;4:538-52.
4. Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ. 2023 ESC Guidelines for the Management of Cardiovascular Disease in Patients with Diabetes. Eur Heart J 2023;44:4043-140.
5. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci 2020;21.
6. Hussain A. Chronic hyperglycemia and cardiovascular dysfunction: an in-depth exploration of metabolic and cellular pathways in type 2 diabetes mellitus. Cardiovasc Diabetol Endocrinol Rep 2025;11:39.
7. González P, Lozano P, Ros G, Solano F. Hyperglycemia and Oxidative Stress: An Integral, Updated and Critical Overview of Their Metabolic Interconnections. Int J Mol Sci 2023;24:9352.
8. Hudspeth B, PharmD C. The burden of cardiovascular disease in patients with diabetes. Am J Manag Care 2018;24:S268-S272.
9. Djuric D, Bajic Z, Radisavljevic N, Sobot T, Mutavdzin Krneta S, Stankovic S, et al. High-Sensitivity Troponins and Homocysteine: Combined Biomarkers for Better Prediction of Cardiovascular Events. Int J Mol Sci 2025;26.
10. Mou L, Fu Z, Wang TB, Chen Y, Luo Z, Wang X, et al. Na+/K±ATPase: a multifunctional target in type 2 diabetes and pancreatic islets. Front Immunol 2025;16:1555310.
11. Wong ND, Sattar N. Cardiovascular risk in diabetes mellitus: epidemiology, assessment and prevention. Nat Rev Cardiol 2023;20:685-95.
12. LeBlanc ES, Brooks N, Davies M, Chatterjee R. Sex-Specific Cardiovascular Risk Factors and Treatment in Females With T2DM and CVD: Developments and Knowledge Gaps. J Clin Endocrinol Metab 2024;109:e2167-77.
13. Al-Salameh A, El bouzegaoui N, Saraval-Gross M. Diabetes and cardiovascular risk according to sex: An overview of epidemiological data from the early Framingham reports to the cardiovascular outcomes trials. Ann Endocrinol 2023;84:57-68.
14. Khan AW, Jandeleit-Dahm KA. Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches. Nat Rev Cardiol 2025;22:482-96.
15. Béliard S, Mourre F, Valéro R. Hyperlipidaemia in diabetes: are there particular considerations for next-generation therapies? Diabetologia 2024;67:974-84.
16. Sabitha S, Hegde SV, Agarwal SV, Delna N, Pillai A, Shah SN, et al. Biomarkers of oxidative stress and their clinical relevance in type 2 diabetes mellitus patients: a systematic review. Cureus 2024;16.
17. Li X, Zou J, Lin A, Chi J, Hao H, Chen H, et al. Oxidative stress, endothelial dysfunction, and N-acetylcysteine in type 2 diabetes mellitus. Antioxid Redox Signal 2024;40:968-89.
18. Rajlic S, Treede H, Münzel T, Daiber A, Duerr GD. Early detection is the best prevention—characterization of oxidative stress in diabetes mellitus and its consequences on the cardiovascular system. Cells 2023;12:583.
19. Unadkat SV, Padhi BK, Bhongir AV, Gandhi AP, Shamim MA, Dahiya N, et al. Association between homocysteine and coronary artery disease—trend over time and across the regions: a systematic review and meta-analysis. Egypt Heart J 2024;76:29.
20. Mokgalaboni K, Mashaba GR, Phoswa WN, Lebelo SL. Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials. Nutr Diabetes 2024;14:22.
21. Dhalla NS, Elimban V, Adameova AD. Role of Na±K+ ATPase alterations in the development of heart failure. Int J Mol Sci 2024;25:10807.
22. Elezaby A, Lin AJ, Vijayan V, Pokhrel S, Kraemer BR, Bechara LR, et al. Cardiac troponin I directly binds and inhibits mitochondrial ATP synthase with a noncanonical role in the post-ischemic heart. Nat Cardiovasc Res 2024;3:987-1002.
23. Contreras RG, Torres-Carrillo A, Flores-Maldonado C, Shoshani L, Ponce A. Na+/K±ATPase: more than an electrogenic pump. Int J Mol Sci 2024;25:6122
24. McEvoy JW, Mangan C. Predicting Incident CVD Risk With High-Sensitivity Cardiac Troponin: Mainstream, Niche, or Neither? Washington DC: American College of Cardiology Foundation; 2024
25. Li J, Pan L, Pan W, Li N, Tang B. Recent progress of oxidative stress associated biomarker detection. Chem Commun 2023;59:7361-74.
26. Luciani L, Pedrelli M, Parini P. Modification of lipoprotein metabolism and function driving atherogenesis in diabetes. Atherosclerosis 2024;394:117545
27. Lee DY. Emerging circulating biomarkers for enhanced cardiovascular risk prediction. J Lipid Atheroscler 2024;13:262-79
28. Wilson M, Al‐Hamid A, Abbas I, Birkett J, Khan I, Harper M, et al. Identification of diagnostic biomarkers used in the diagnosis of cardiovascular diseases and diabetes mellitus: A systematic review of quantitative studies. Diabetes Obes Metab 2024;26:3009-19.
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IssueVol 64 No 9 (2026) QRcode
SectionOriginal Articles
Keywords
Type 2 diabetes mellitus Acute coronary syndrome Na /K -ATPase Homocysteine Oxidative stress Cardiac troponin

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How to Cite
1.
Jwaid SH, Ahmed HF. Integrated Oxidative and Cardiac Biomarker Profile in Type 2 Diabetes Mellitus With Acute Coronary Syndrome. Acta Med Iran. 2026;64(9):564-572.