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

DOI:

https://doi.org/10.14419/3dypmj38

Published

04-11-2025

Keywords:

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Gupta, A., Upadhyay, A., & Kakar, A. (2021). Role of TNF-α in non-healing diabetic foot ulcers. Wound Medicine, 32, 100390.

Hajian-Tilaki, K. (2013). Receiver operating characteristic (ROC) curve analysis for medical diagnostic test evaluation. Caspian Journal of Internal Medicine, 4(2), 627–635.

Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860–867. https://doi.org/10.1038/nature05485.

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.

Kadhim, A. S. (2021). Role of cytokine imbalance in diabetic foot ulcer pathogenesis. Journal of Diabetes and Endocrinology Research, 10(2), 45–51.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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