Assessment of Immunological Biomarkers in Diabetic Patients with and without Foot Ulcers

  • Authors

    • Aseel Abd Ulameer Kamas‏ ‏ Al-Khalidi College of Science, University of Al- Al-Qadisiyah, Iraq
    • Rasha Muzahem Hatem College of Science, University of Al- Al-Qadisiyah, Iraq
    https://doi.org/10.14419/3dypmj38

    Received date: July 21, 2025

    Accepted date: September 24, 2025

    Published date: November 4, 2025

  • Diabetes Mellitus; Diabetic Foot Ulcer; Cytokines; IL-10; IL-18; TNF-α; Bfgf.
  • Abstract

    Ulcers of the foot caused by diabetes (DFU) are among the most severe consequences of diabetes mellitus, significantly diminishing ‎patients’ quality of life and often resulting in persistent infections and potential limb loss. This study aimed to assess the serum levels ‎of four immunological biomarkers: interleukin-10 (IL-10), interleukin-18 (IL-18), tumor necrosis factor-alpha (TNF-α), and basic ‎fibroblast growth factor (bFGF) in patients with diabetes and in patients without foot ulcers, as well as in healthy participants. The ‎study enrolled 90 participants, including diabetic patients with foot ulcers, diabetic patients without ulcers, and healthy controls. ‎Then, the Blood samples were collected and analyzed using ELISA to determine serum concentrations of IL-10, IL-18, TNF-α, and ‎bFGF. Statistical analyses included ANOVA, Duncan's multiple range test, and ROC curve evaluation. The results indicate that IL-18 ‎and TNF-α levels were significantly elevated in both diabetic groups compared to controls (P < 0.001), indicating persistent systemic ‎inflammation. IL-10 levels were significantly higher in diabetics without ulcers than in controls (P < 0.05), suggesting a compensatory ‎anti-inflammatory response. Interestingly, bFGF was significantly elevated in patients with ulcers (P < 0.001), potentially reflecting a ‎local reparative response. ROC analysis revealed that bFGF had high diagnostic accuracy (AUC = 0.809) in differentiating DFU ‎patients from healthy individuals. The finding highlighted that the observed cytokine profiles suggest that DFUs are characterized by ‎an inflammatory–reparative imbalance. Elevated IL-18 and TNF-α indicate sustained inflammation, while reduced IL-10 and ‎altered bFGF levels reflect impaired resolution and tissue repair mechanisms. These markers, particularly bFGF, show promise as ‎potential diagnostic tools for identifying and monitoring DFU progression‎.

  • References

    1. Aggarwal, B. B., Gupta, S. C., & Kim, J. H. (2014). Regulation of survival, proliferation, invasion, angiogenesis, and metastasis of tumor cells through modulation of inflammatory pathways by nutraceuticals. Cancer and Metastasis Reviews, 33(2–3), 351–368.
    2. Al-Rubeaan, K., Al Derwish, M., Ouizi, S., Youssef, A. M., Subhani, S. N., Ibrahim, H. M., & Alamri, B. N. (2015). Diabetic foot complications and their risk factors from a large retrospective cohort study. PLoS ONE, 10(5), e0124446. https://doi.org/10.1371/journal.pone.0124446.
    3. Al-Salih, M. I., Al-Dujaili, A. H., & Khalaf, A. F. (2021). Oxidative stress and endothelial dysfunction in type 2 diabetic patients with and without foot ulcer: A comparative study. Iraqi Journal of Medical Sciences, 19(3), 380–389.
    4. Anyim, O., Onwubere, B. J., Njoku, C. H., & Onyemelukwe, G. C. (2019). Cost and burden of diabetic foot ulcers in sub-Saharan Africa: A Nige-rian experience. International Journal of Diabetes in Developing Countries, 39(3), 567–574.
    5. Byrnes, J., Ward, L., Jensen, S., Sagoo, M., Charles, D., Mann, R., ... & Lazzarini, P. A. (2024). Health-related quality of life in people with differ-ent diabetes-related foot ulcer health states: A cross-sectional study of healed, non-infected, infected, hospitalised and amputated ulcer states. Diabetes research and clinical practice, 207, 111061.‏ https://doi.org/10.1016/j.diabres.2023.111061.
    6. Cho, N. H., Shaw, J. E., Karuranga, S., Huang, Y., da Rocha Fernandes, J. D., Ohlrogge, A. W., & Malanda, B. (2018). IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Research and Clinical Practice, 138, 271–281. https://doi.org/10.1016/j.diabres.2018.02.023.
    7. Dinarello, C. A. (2018). Overview of the IL-1 family in innate inflammation and acquired immunity. Immunological Reviews, 281(1), 8–27. https://doi.org/10.1111/imr.12621.
    8. Donath, M. Y., & Shoelson, S. E. (2011). Type 2 diabetes as an inflammatory disease. Nature Reviews Immunology, 11(2), 98–107. https://doi.org/10.1038/nri2925.
    9. Esposito, K., Nappo, F., Marfella, R., Giugliano, G., & Giugliano, D. (2002). Inflammatory cytokine concentrations are acutely increased by hyper-glycemia in humans. Circulation, 106(16), 2067–2072. https://doi.org/10.1161/01.CIR.0000034509.14906.AE.
    10. Falanga, V. (2005). Wound healing and its impairment in the diabetic foot. The Lancet, 366(9498), 1736–1743. https://doi.org/10.1016/S0140-6736(05)67700-8.
    11. Ghosh, P., Ghosh, S., & Ghosh, M. (2024). Evaluation of IL-10 as a biomarker in diabetic foot ulcer patients: A clinical study. Journal of Diabetes Research and Clinical Metabolism, 13(1), 23–30.
    12. Gupta, A., Upadhyay, A., & Kakar, A. (2021). Role of TNF-α in non-healing diabetic foot ulcers. Wound Medicine, 32, 100390.
    13. Hajian-Tilaki, K. (2013). Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian Journal of Internal Medicine, 4(2), 627–635.
    14. Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860–867. https://doi.org/10.1038/nature05485.
    15. Ip, W. K. E., Hoshi, N., Shouval, D. S., Snapper, S., & Medzhitov, R. (2016). Anti-inflammatory function of interleukin-10 produced by regulatory T cells during innate immune responses. Immunity, 44(4), 860–871. https://doi.org/10.1016/j.immuni.2016.03.014.
    16. Kadhim, A. S. (2021). Role of cytokine imbalance in diabetic foot ulcer pathogenesis. Journal of Diabetes and Endocrinology Research, 10(2), 45–51.
    17. Li, X., Zhang, Z., Li, L., & Wang, Y. (2015). Effect of basic fibroblast growth factor on wound healing in patients with diabetic foot ulcers: A me-ta-analysis. World Journal of Emergency Medicine, 6(2), 82–89.
    18. Liu, Y., Zhang, J., & Wang, C. (2022). Interleukin-10 as a biomarker in diabetic foot ulcers. Biochemical and Biophysical Research Communica-tions, 602, 73–78. https://doi.org/10.1016/j.bbrc.2022.03.017.
    19. Mirza, R. E., Fang, M. M., Ennis, W. J., & Koh, T. J. (2014). Blocking interleukin-1β induces a healing-associated wound macrophage phenotype and improves healing in type 2 diabetes. Diabetes, 62(7), 2579–2587. https://doi.org/10.2337/db13-1614.
    20. Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O’Garra, A. (2001). Interleukin-10 and the interleukin-10 receptor. Annual Review of Im-munology, 19, 683–765. https://doi.org/10.1146/annurev.immunol.19.1.683.
    21. Netea, M. G., Joosten, L. A. B., Lewis, E., Jensen, D. R., Voshol, P. J., Kullberg, B. J., & van der Meer, J. W. M. (2010). Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nature Medicine, 12(6), 650–656. https://doi.org/10.1038/nm1405.
    22. Pepe, M. S., Janes, H., Longton, G., Leisenring, W., & Newcomb, P. (2001). Limitations of the odds ratio in gauging the performance of a diagnos-tic, prognostic, or screening marker. American Journal of Epidemiology, 159(9), 882–890. https://doi.org/10.1093/aje/kwi103.
    23. Yousif, D., Yousif, Z., & Joseph, P. (2024). Diabetic Foot Ulcer Neuropathy, Impaired Vasculature, and Immune Responses. In Diabetic Foot Ul-cers-Pathogenesis, Innovative Treatments and AI Applications. IntechOpen.‏ https://doi.org/10.5772/intechopen.1003834.
    24. Mohsin, F., Javaid, S., Tariq, M., & Mustafa, M. (2024). Molecular immunological mechanisms of impaired wound healing in diabetic foot ulcers (DFU), current therapeutic strategies and future directions. International Immunopharmacology, 139, 112713.‏ https://doi.org/10.1016/j.intimp.2024.112713.
    25. Singh, Aditi, et al. "Type 2 diabetes mellitus: A comprehensive review of pathophysiology, comorbidities, and emerging therapies." Comprehensive Physiology 15.1 (2025): e70003.‏ https://doi.org/10.1002/cph4.70003.
    26. Pickup, J. C. (2004). Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care, 27(3), 813–823. https://doi.org/10.2337/diacare.27.3.813.
    27. Zhang, P., Lu, J., Jing, Y., Tang, S., Zhu, D., & Bi, Y. (2017). Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis. Annals of Medicine, 49(2), 106–116. https://doi.org/10.1080/07853890.2016.1231932.
    28. Zhang, Y., Wang, Q., Zhao, H., & Li, X. (2020). Elevated interleukin-18 levels in patients with diabetic foot ulcers. Wound Repair and Regenera-tion, 28(1), 62–68. https://doi.org/10.1111/wrr.12715.
    29. Zhang, Z., Li, X., & Li, L. (2021). The predictive role of local and serum TNF-α levels in diabetic foot ulcer severity. Journal of Inflammation Re-search, 14, 1201–1210.
    30. Zhou, Z., Liu, Y., & Duan, H. (2011). Diagnostic value of basic fibroblast growth factor in diabetic foot ulcers. Wound Repair and Regeneration, 19(6), 720–726. https://doi.org/10.1111/j.1524-475X.2011.00746.x.
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  • How to Cite

    Al-Khalidi , A. A. U. K. ‏, & Hatem, R. M. . (2025). Assessment of Immunological Biomarkers in Diabetic Patients with and without Foot Ulcers. International Journal of Basic and Applied Sciences, 14(7), 88-96. https://doi.org/10.14419/3dypmj38