Oxidative Stress in Diabetes mellitus and the Role of Antioxidants in Reducing Its Complications
DOI:
https://doi.org/10.54153/sjpas.2026.v8i1.1344Keywords:
Oxidative stress, Antioxidant, diabetes mellitusAbstract
An imbalance between free radicals and the antioxidant systems that are essential for neutralizing them leads to oxidative stress. Reduce the accumulation of free radicals and contribute to reducing oxidative stress levels in the body, antioxidants are crucial. Type 1 diabetes results from the body's incapacity insulin secretion because the beta cells in the pancreas have been destroyed due to the autoimmune destruction of these cells, while Type 2 diabetes is caused by decreased insulin release from the pancreas. Both kinds result in high blood glucose levels, and if left unchecked, persistent hyperglycemia can cause major problems..Persistent high blood glucose promotes increased generation of free radicals via multiple metabolic pathways, involving the production of advanced glycation end products (AGEs), the hexosamine route, the polyol pathway, and glucose oxidation, all of which lead to oxidative stress. The microvascular and macrovascular problems associated with diabetes are made worse by this oxidative stress. Antioxidants are essential in this situation because they neutralize the generation of free radicals, avoiding oxidative stress and problems associated with diabetes.
References
1. Forman, H. J., & Zhang, H. (2021). Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nature Reviews Drug Discovery, 20(9), 689-709. https://doi.org/10.1038/s41573-021-00233-1
2. Badawi, A., Klip, A., Haddad, P., Cole, D. E., Bailo, B. G., El-Sohemy, A., & Karmali, M. (2010). Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention. Diabetes, metabolic syndrome and obesity: targets and therapy, 173-186. https://doi.org/10.2147/dmso.s9089
3. Halliwell, B., & Gutteridge, J. M. (2015). Free radicals in biology and medicine. Oxford university press. https://doi.org/10.1093/acprof:oso/9780198717478.003.0002
4. Sindhi, V., Gupta, V., Sharma, K., Bhatnagar, S., Kumari, R., & Dhaka, N. (2013). Potential applications of antioxidants—A review. Journal of Pharmaceutical Research, 7, 828–835. https://doi.org/10.1016/j.jopr.2013.10.001
5. Federation, I. D. (2021). IDF Diabetes Atlas 2021. International Diabetes Federation. https://doi.org/10.1136/bmjdrc-2021-002122
6. Trujillo, J., & Haines, S. T. (2020). Diabetes mellitus. In J. T. DiPiro, G. C. Yee, L. M. Posey, S. T. Haines, T. D. Nolin, & V. L. Ellingrod (Eds.), Pharmacotherapy: A pathophysiologic approach (11th ed.). McGraw-Hill Education. https://doi.org/10.1345/aph.1l477
7. Ozougwu, C. J., Obimba, C. K., Belonwu, D. C., & Unakalamba, B. C. (2013). The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. Journal of Physiology and Pathophysiology, 4, 46–57. https://doi.org/10.5897/JPAP2013.0001
8. DeFronzo, R. A., Ferrannini, E., Groop, L., et al. (2015). Type 2 diabetes mellitus. Nature Reviews Disease Primers, 1, Article 15019. https://doi.org/10.1038/nrdp.2015.19
9. Chatterjee, S., Khunti, K., & Davies, M. J. (2017). Type 2 diabetes. The Lancet, 389, 2239–2251. https://doi.org/10.1016/S0140-6736(17)30058-2
10. Katsarou, A., Gudbjörnsdottir, S., Rawshani, A., et al. (2017). Type 1 diabetes mellitus. Nature Reviews Disease Primers, 3, Article 17016. https://doi.org/10.1038/nrdp.2017.16 11. Zhao, M., Wang, S., Zuo, A., Zhang, J., Wen, W., Jiang, W., … & Wang, M. (2021). HIF-1α/JMJD1A signaling regulates inflammation and oxidative stress following hyperglycemia and hypoxia-induced vascular cell injury. Cellular & Molecular Biology Letters, 26(1), 40. https://doi.org/10.1186/s11658-021-00283-2 12. Sharifi-Rad M., Lankatillake C., Dias D. A., Docea A. O., Mahomoodally M. F., Lobine D., et al. (2020). Impact of natural compounds on neurodegenerative disorders: from preclinical to pharmacotherapeutics. J. Clin. Med. 9:1061. https://doi.org/10.3390/jcm9041061 13. Sies, H., Belousov, V. V., Chandel, N. S., Davies, M. J., Jones, D. P., Mann, G. E., … & Winterbourn, C. (2022). Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nature reviews Molecular cell biology, 23(7), 499-515. https://doi.org/10.1038/s41580-022-00456-z 14. Apak, R., Calokerinos, A., Gorinstein, S., Segundo, M. A., Hibbert, D. B., Gülçin, İ., … & Arancibia-Avila, P. (2022). Methods to evaluate the scavenging activity of antioxidants toward reactive oxygen and nitrogen species (IUPAC Technical Report). Pure and Applied Chemistry, 94(1), 87-144. https://doi.org/10.1515/pac-2020-090
15. Aranda-Rivera, A. K., Cruz-Gregorio, A., Arancibia-Hernández, Y. L., Hernández-Cruz, E. Y., & Pedraza-Chaverri, J. (2022). RONS and oxidative stress: an overview of basic concepts. Oxygen, 2(4), 437-478. https://doi.org/10.3390/oxygen2040030
16. Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiological Reviews, 94(3), 909–950. https://doi.org/10.1152/physrev.00026.2013 17. Chaudhary, P., Singh, D., Swapnil, P., Meena, M., and Janmeda, P. (2023). Euphorbia neriifolia (Indian spurge tree): A plant of multiple biological and pharmacological activities. Sustainability 15(2), 1225. https://doi.org/10.3390/su15021225 18. Korczowska‑Łącka, I., Słowikowski, B., Piekut, T., Hurła, M., Banaszek, N., Szymanowicz, O., Jagodziński, P. P., Kozubski, W., Permoda‑Pachuta, A., & Dorszewska, J. (2023). Disorders of Endogenous and Exogenous Antioxidants in Neurological Diseases. Antioxidants, 12(10), 1811. https://doi.org/10.3390/antiox12101811 19. Kurutas, E. B. (2016). The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutrition Journal, 15(1):71. https://doi.org/10.1186/s12937-016-0186-5
20. Bouayed, J., & Bohn, T. (2010). Exogenous antioxidants—Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative medicine and cellular longevity, 3(4), 228–237. https://doi.org/10.4161/oxim.3.4.12858 21. Centers for Disease Control and Prevention. (2022, November 11). National diabetes statistics report. U.S. Department of Health and Human Services. https://doi.org/10.3886/icpsr09705.v2 22. Daghlas, S. A., & Mohiuddin, S. S. (2023). Biochemistry, Glycogen. In StatPearls. StatPearls Publishing. https://doi.org/10.2337/cd22-as01 23. Hill, M. A., Yang, Y., Zhang, L., et al. (2021). Insulin resistance, cardiovascular stiffening and cardiovascular disease. Metabolism, 119, Article 154766. https://doi.org/10.1016/j.metabol.2021.154766 24. DiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018). Type 1 diabetes. Lancet, 391(10138), 2449–2462. https://doi.org/10.1016/S0140-6736(18)31320-5 25. American Diabetes Association. (2021). Standards of medical care in diabetes—2022: Abridged for primary care providers. Clinical Diabetes, 40(1). https://doi.org/10.2337/cd21-as01
26. Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., et al. (2020). Pathophysiology of type 2 diabetes mellitus. International Journal of Molecular Sciences, 21(17), 6275. https://doi.org/10.3390/ijms21176275 27. Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H. P., Giardino, I., & Brownlee, M. (2000). Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 404(6779), 787–790. https://doi.org/10.1038/35008121 28. Styskal, J., Van Remmen, H., Richardson, A., & Salmon, A. B. (2012). Oxidative stress and diabetes: what can we learn about insulin resistance from antioxidant mutant mouse models?. Free radical biology and medicine, 52(1), 46-58. https://doi.org/10.1016/j.freeradbiomed.2011.10.441
29. Cho, S. J., Roman, G., Yeboah, F., & Konishi, Y. (2007). The road to advanced glycation end products: a mechanistic perspective. Current medicinal chemistry, 14(15), 1653-1671. https://doi.org/10.2174/092986707780830989 30. Nagai, R., Shirakawa, J. I., Ohno, R. I., Moroishi, N., & Nagai, M. (2014). Inhibition of AGEs formation by natural products. Amino Acids, 46(2), 261-266. https://doi.org/10.1007/s00726-013-1487-z 31. Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414(6865), 813-820. https://doi.org/10.1038/414813a
32. Scivittaro, V., Ganz, M. B., & Weiss, M. F. (2000). AGEs induce oxidative stress and activate protein kinase C-βII in neonatal mesangial cells. American Journal of Physiology-Renal Physiology, 278(4), F676-F683. https://doi.org/10.1152/ajprenal.2000.278.4.f676 33. Nishizuka, Y. (1995). Protein kinase C and lipid signaling for sustained cellular responses. The FASEB journal, 9(7), 484-496. https://doi.org/10.1096/fasebj.9.7.7737456 34. Robertson, R. P. (2004). Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. Journal of Biological Chemistry, 279(41), 42351-42354. https://doi.org/10.1074/jbc.r400019200 35. Figueroa-Romero, C., Sadidi, M., & Feldman, E. L. (2008). Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Reviews in Endocrine and Metabolic Disorders, 9(4), 301-314. https://doi.org/10.1007/s11154-008-9104-2 36. Morales-Gonzalez, J. A. (Ed.). (2013). Oxidative stress and chronic degenerative diseases: A role for antioxidants. BoD–Books on Demand. https://doi.org/10.5772/45722
37. Schleicher, E. D., & Weigert, C. (2000). Role of the hexosamine biosynthetic pathway in diabetic nephropathy. Kidney international, 58, S13-S18. https://doi.org/10.1046/j.1523-1755.2000.07703.x 38. Caturano, A., D’Angelo, M., Mormone, A., Russo, V., Mollica, M. P., Salvatore, T., … & Sasso, F. C. (2023). Oxidative stress in type 2 diabetes: impacts from pathogenesis to lifestyle modifications. Current Issues in Molecular Biology, 45(8), 6651-6666. https://doi.org/10.3390/cimb45080420
39. Fowler, M. J. (2008). Microvascular and macrovascular complications of diabetes. Clinical Diabetes, 26(2), 77-82. https://doi.org/10.2337/diaclin.26.2.77 40. Thomas, M. C. (2011). Advanced glycation end products. Contributions to Nephrology, 170, 66-74. https://doi.org/10.1159/000324945 41. American Diabetes Association. (2021). Standards of medical care in diabetes—2022: Abridged for primary care providers. Clinical Diabetes, 40(1). https://doi.org/10.2337/cd22-as01 42. Sheikh-Ali, M., Chehade, J. M., & Mooradian, A. D. (2011). The antioxidant paradox in diabetes mellitus. American Journal of Therapeutics, 18(3), 266–278. https://doi.org/10.1097/mjt.0b013e3181b7badf 43. Mayer-Davis, E. J., Costacou, T., King, I., Zaccaro, D. J., & Bell, R. A. (2002). Plasma and dietary vitamin E in relation to incidence of type 2 diabetes: The Insulin Resistance and Atherosclerosis Study (IRAS). Diabetes Care, 25(12), 2172–2177. https://doi.org/10.2337/diacare.25.12.2172
44. Cuerda C. Luengo L. M. MA Valero Vidal. A. Burgos R. Calvo F. L. et al. (2011). Antioxidants and diabetes mellitus: review of the evidence. Nutr Hosp 26(1), 68-78. https://doi.org/10.1055/s-0033-1333688 45. Garcia-Bailo B. El-Sohemy A. Haddad P. S. Arora P. Benzaied F. Karmali M. et al. (2011). Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress. Biologics 5, 7-19. https://doi.org/10.5772/47834 46. Jeffrey, S., Isaac Samraj, P., & Sundara Raj, B. (2022). Therapeutic benefits of alpha-lipoic acid supplementation in diabetes mellitus: a narrative review. Journal of dietary supplements, 19(4), 566-586. https://doi.org/10.1080/19390211.2021.2020387 47. Vakali, E., Rigopoulos, D., Carrillo, A. E., Flouris, A. D., & Dinas, P. C. (2022). Effects of alpha-lipoic acid supplementation on human diabetic nephropathy: A systematic review and meta-analysis. Current diabetes reviews, 18(6), 43-50. https://doi.org/10.2174/1573399817666210914103329 48. Akbaraly, T. N., Fontbonne, A., Favier, A., & Berr, C. (2008). Plasma carotenoids and onset of dysglycemia in an elderly population: results of the Epidemiology of Vascular Ageing Study. Diabetes Care, 31(7), 1355-1359. https://doi.org/10.2337/dc07-2113 49. Hozawa, A., Jacobs Jr, D. R., Steffes, M. W., Gross, M. D., Steffen, L. M., & Lee, D. H. (2006). Associations of serum carotenoid concentrations with the development of diabetes and with insulin concentration: interaction with smoking: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. American journal of epidemiology, 163(10), 929-937. https://doi.org/10.1093/aje/kwj136 50. Roohbakhsh, A., Karimi, G., & Iranshahi, M. (2017). Carotenoids in the treatment of diabetes mellitus and its complications: A mechanistic review. Biomedicine & Pharmacotherapy, 91, 31-42. https://doi.org/10.1016/j.biopha.2017.04.057 51. Neyestani, T. R., Shariatzadeh, N., Gharavi, A., Kalayi, A., & Khalaji, N. (2007). Physiological dose of lycopene suppressed oxidative stress and enhanced serum levels of immunoglobulin M in patients with Type 2 diabetes mellitus: a possible role in the prevention of long-term complications. Journal of endocrinological investigation, 30(10), 833-838. https://doi.org/10.1007/bf03349226 52. Lem, D. W., Gierhart, D. L., & Davey, P. G. (2021). A systematic review of carotenoids in the management of diabetic retinopathy. Nutrients, 13(7), 2441. https://doi.org/10.3390/nu13072441 53. Moschos, M. M., Dettoraki, M., Tsatsos, M., Kitsos, G., & Kalogeropoulos, C. (2017). Effect of carotenoids dietary supplementation on macular function in diabetic patients. Eye and visión, 4(1), 23. https://doi.org/10.1186/s40662-017-0088-4 54. Behrouz, V., Sohrab, G., Hedayati, M., & Sedaghat, M. (2021). Inflammatory markers response to crocin supplementation in patients with type 2 diabetes mellitus: a randomized controlled trial. Phytotherapy Research, 35(7), 4022-4031. https://doi.org/10.1002/ptr.7124 55. Zhang, J., Chen, Y., Zou, L., Jin, L., Yang, B., Shu, Y., & Gong, R. (2023). Dose–response relationship between dietary antioxidant intake and diabetic kidney disease in the US adults with diabetes. Acta Diabetologica, 60(10), 1365-1375. https://doi.org/10.1007/s00592-023-02125-2
56. Ghorbani, A. (2017). Mechanisms of antidiabetic effects of flavonoid rutin. Biomedicine & Pharmacotherapy, 96, 305-312. https://doi.org/10.1016/j.biopha.2017.10.001 57. Bondonno, N. P., Dalgaard, F., Murray, K., Davey, R. J., Bondonno, C. P., Cassidy, A., … & Hodgson, J. M. (2021). Higher habitual flavonoid intakes are associated with a lower incidence of diabetes. The Journal of nutrition, 151(11), 3533-3542. https://doi.org/10.1093/jn/nxab269
58. Dinda, B., Dinda, M., Roy, A., & Dinda, S. (2020). Dietary plant flavonoids in prevention of obesity and diabetes. Advances in protein chemistry and structural biology, 120, 159-235. https://doi.org/10.1016/bs.apcsb.2019.08.006
59. Guo, X. F., Ruan, Y., Li, Z. H., & Li, D. (2019). Flavonoid subclasses and type 2 diabetes mellitus risk: a meta-analysis of prospective cohort studies. Critical reviews in food science and nutrition, 59(17), 2850-2862. https://doi.org/10.1080/10408398.2018.1476964 60. Yeon, J. Y., Bae, Y. J., Kim, E. Y., & Lee, E. J. (2015). Association between flavonoid intake and diabetes risk among the Koreans. Clinica Chimica Acta, 439, 225-230. https://doi.org/10.1016/j.cca.2014.10.04
61. Søndergård, S. D., Cintin, I., Kuhlman, A. B., Morville, T. H., Bergmann, M. L., Kjær, L. K., … & Larsen, S. (2021). The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial. Applied Physiology, Nutrition, and Metabolism, 46(9), 1133-1142. https://doi.org/10.1139/apnm-2020-1099 62. Kalamkar, S., Acharya, J., Kolappurath Madathil, A., Gajjar, V., Divate, U., Karandikar-Iyer, S., … & Ghaskadbi, S. (2022). Randomized clinical trial of how long-term glutathione supplementation offers protection from oxidative damage and improves HbA1c in elderly type 2 diabetic patients. Antioxidants, 11(5), 1026. https://doi.org/10.3390/antiox11051026
63. To, K., Cao, R., Yegiazaryan, A., Owens, J., Nguyen, T., Sasaninia, K., … & Venketaraman, V. (2021). Effects of oral liposomal glutathione in altering the immune responses against Mycobacterium tuberculosis and the Mycobacterium bovis BCG strain in individuals with type 2 diabetes. Frontiers in Cellular and Infection Microbiology, 11, 657775. https://doi.org/10.3389/fcimb.2021.657775
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