https://doi.org/10.4081/jbr.2026.14830
Study on the leukocytes infiltration and association in diabetic foot ulceration patients
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Published: 9 June 2026
Diabetic foot ulcers are among the most common problems facing the people with diabetes. Leukocytes have been shown to penetrate the region of inflammation in order to regulate the infection. Thus, the current research was designed to study the infiltration of leukocytes in diabetic foot patients. Samples were taken from 50 healthy individuals and 100 diabetic foot ulcer patients. Levels of Fasting Blood Sugar (FBS), Hemoglobin A1C (HbA1c), cholesterol, triglycerides, urea, and creatinine were measured. Leukocytes infiltration was also evaluated in the diabetic foot patients. Levels of FBS and HbA1c were significantly increased (p≤ 0.05) in patients with diabetic foot ulceration. In addition, the levels of cholesterol, triglycerides and urea significantly increased (p≤ 0.05) in diabetic foot ulceration patients. However, the levels of creatinine greatly decreased in patients with diabetic foot ulceration. Infiltrated leukocytes were significantly increased in the ulcerated foot. Furthermore, the study found a strong association between leukocyte infiltration and HbA1c as follows: (y = 0.6864x + 0.9455: R² = 0.776). Thus, studying the mechanism of controlling leukocytes in diabetic foot ulcer could greatly participate in healing of diabetic foot ulcers.
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1. Wang X, Yuan C-X, Xu B, Yu Z. Diabetic foot ulcers: Classification, risk factors and management. World J Diabetes 2022;13:1049–65. DOI: https://doi.org/10.4239/wjd.v13.i12.1049
2. Swerdlow MA, Armstrong AA, Conte MS, et al. Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer. J Foot Ankle Res 2020;13:16. DOI: https://doi.org/10.1186/s13047-020-00383-2
3. Lu X, Xie Q, Pan X, et al. Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy. Signal Transduct. Target Ther 2024;9:262. DOI: https://doi.org/10.1038/s41392-024-01951-9
4. Madhi R, Hashim NA, Al-Ali ZAJR, Tahir NT. Estimation of lipid profile and some inflammatory biomarkers in patients with diabetes mellitus type 2 linked to hypertension. J Biol Res 2024;97:12484. DOI: https://doi.org/10.4081/jbr.2024.12484
5. Hashim N, Madhi R, Ali Z, et al. Study on assessment of reproductive hormones in male patients with type 1 and 2 diabetes mellitus. J Adv Biotechnol Exp Ther 2024;7:328. DOI: https://doi.org/10.5455/jabet.2024.d27
6. Wang L, Yan N, Zhang M, et al. The association between blood glucose levels and lipids or lipid ratios in type 2 diabetes patients: A cross-sectional study. Front Endocrinol (Lausanne) 2022;13:96980 . DOI: https://doi.org/10.3389/fendo.2022.969080
7. Nnakenyi I.D, Nnakenyi E.F, Parker, et al. Relationship between glycaemic control and lipid profile in type 2 diabetes mellitus patients in a low-resource setting. Pan Afr Med J 2022;41, 281 . DOI: https://doi.org/10.11604/pamj.2022.41.281.33802
8. Li R, He M, Yang Q, et al. Association between serum creatinine and type 2 diabetes in the Chinese population: a retrospective cohort study. Sci Rep 2023;13:6806.
9. Seki M, Nakayama M, Sakoh T, et al. Blood urea nitrogen is independently associated with renal outcomes in Japanese patients with stage 3-5 chronic kidney disease: a prospective observational study. BMC Nephrol 2019;20:115 . DOI: https://doi.org/10.1186/s12882-019-1306-1
10. D'Apolito M, Du X, Zong H, et al. Urea-induced ROS generation causes insulin resistance in mice with chronic renal failure. J Clin Invest 2010;120:20313. DOI: https://doi.org/10.1172/JCI37672
11. Koppe L, Nyam E, Vivot K, et al. Urea impairs β cell glycolysis and insulin secretion in chronic kidney disease. J Clin Invest 2016;126:3598-612. DOI: https://doi.org/10.1172/JCI86181
12. Madhi R, Algaber, A, Munshid M, Jassim K. Association between neutrophil recruitment and lung inflammation in type I hypersensitivity reaction. World Acad Sci J 2024;6:38. DOI: https://doi.org/10.3892/wasj.2024.253
13. Hawez A, Ding Z, Taha D, et al. c-Abl kinase regulates neutrophil extracellular trap formation and lung injury in abdominal sepsis. Lab Investig 2022;102:2632-71 . DOI: https://doi.org/10.1038/s41374-021-00683-6
14. Clayton SM, Shafikhani SH, Soulika AM. macrophage and neutrophil dysfunction in diabetic wounds. Adv wound care 2024;13:463484. DOI: https://doi.org/10.1089/wound.2023.0149
15. Zhu S, Yu Y, Ren Y,et al. The emerging roles of neutrophil extracellular traps in wound healing. Cell Death Dis 2021;12:984. DOI: https://doi.org/10.1038/s41419-021-04294-3
16. Yang S, Wang S, Chen L, et al. Neutrophil extracellular traps delay diabetic wound healing by inducing endothelial-to-mesenchymal transition via the Hippo pathway. Int J Biol Sci 2023;19:347361. DOI: https://doi.org/10.7150/ijbs.78046
17. Liu D, Yang P, Gao M, et al. NLRP3 activation induced by neutrophil extracellular traps sustains inflammatory response in the diabetic wound. Clin Sci (Lond) 2019;33:565582 . DOI: https://doi.org/10.1042/CS20180600
18. Soares MM, Boyko EJ, Jeffcoate W, et al. Diabetic foot ulcer classifications: A critical review. Diabetes. Metab. Res. Rev. 2020;36 . DOI: https://doi.org/10.1002/dmrr.3272
19. Peterson T, Spitsbergen J, Feist S, Kent M. Luna stain, an improved selective stain for detection of microsporidian spores in histologic sections. Dis Aquat Organ 2011;95:175180. DOI: https://doi.org/10.3354/dao02346
20. Almobarak AO, Awadalla H, Osman M, Ahmed MH. Prevalence of diabetic foot ulceration and associated risk factors: an old and still major public health problem in Khartoum, Sudan? Ann Transl Med 2017;5:340. DOI: https://doi.org/10.21037/atm.2017.07.01
21. Abuhay HW, Yenit MK, Wolde HF. Incidence and predictor of diabetic foot ulcer and its association with change in fasting blood sugar among diabetes mellitus patients at referral hospitals in Northwest Ethiopia. PLoS One 2022;17:e0274754. DOI: https://doi.org/10.1371/journal.pone.0274754
22. Din N, Khan M, Khan B, Ghaffar T. Association of severity of diabetic foot ulcer with glycated hemoglobin A1C levels. Pakistan J Heal Sci 2023;161–5. DOI: https://doi.org/10.54393/pjhs.v4i01.497
23. Christman AL, Selvin E, Margolis DJ, et al. Hemoglobin A1c predicts healing rate in diabetic wounds. J Invest Dermatol 2011;131:21217. DOI: https://doi.org/10.1038/jid.2011.176
24. Hirano T. Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 2018;25:771782. DOI: https://doi.org/10.5551/jat.RV17023
25. Parhofer K.G. Interaction between glucose and lipid metabolism: more than diabetic dyslipidemia. Diabetes Metab J 2015;39:35362. DOI: https://doi.org/10.4093/dmj.2015.39.5.353
26. Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013;139-239. DOI: https://doi.org/10.1155/2013/139239
27. Kopych V, Da Costa ADS, Park K. Endothelial dysfunction in atherosclerosis: experimental models and therapeutics. Biomater Res 2025;29:0252. DOI: https://doi.org/10.34133/bmr.0252
28. Hashim N, Madhi R, Qassem S, Sayhood A. Study on the link of autoimmune hypothyroidism with biochemical parameters and lipid profile in patients with autoimmune thyroid disease. J Adv Biotechnol Exp Ther 2025;8:383. DOI: https://doi.org/10.5455/jabet.2025.31
29. Du J, Zhang W, Niu J, Wang S. Association between blood urea nitrogen levels and the risk of diabetes mellitus in Chinese adults: secondary analysis based on a multicenter, retrospective cohort study. Front Endocrinol (Lausanne) 2024;15:1282015. DOI: https://doi.org/10.3389/fendo.2024.1282015
30. D'Apolito M, Du X, Pisanelli D, et al. Urea-induced ROS cause endothelial dysfunction in chronic renal failure. Atherosclerosis 2015;239:393400. DOI: https://doi.org/10.1016/j.atherosclerosis.2015.01.034
31. Harita N, Hayashi T, Kogawa Sato K, et al. Lower serum creatinine is a new risk factor of type 2 diabetes: the Kansai healthcare study. Diabetes Care 2009;32:4246. DOI: https://doi.org/10.2337/dc08-1265
32. Hu H, Nakagawa T, Honda T, et al. Low serum creatinine and risk of diabetes: The Japan epidemiology collaboration on occupational health study. J Diabetes Investig 2019;10:12091-214. DOI: https://doi.org/10.1111/jdi.13024
33. Li R, He M, Yang Q, et al. Association between serum creatinine and type 2 diabetes in the Chinese population: a retrospective cohort study. Sci Rep 2023;13:6806. DOI: https://doi.org/10.1038/s41598-023-33878-6
34. Dawi J, Tumanyan K, Tomas K, et al. Diabetic foot ulcers: pathophysiology, immune dysregulation, and emerging therapeutic strategies. Biomedicines 2025;13:1076. DOI: https://doi.org/10.3390/biomedicines13051076
35. Lavery LA, Armstrong DG, Quebedeaux TL, Walker SC. Puncture wounds: normal laboratory values in the face of severe infection in diabetics and non-diabetics. Am J Med 1996;101:5215. DOI: https://doi.org/10.1016/S0002-9343(96)00283-5
36. Alexander M, Cho E, Gliozheni E, et al. Pathology of diabetes-induced immune dysfunction. Int J Mol Sci 2024;25:7105. DOI: https://doi.org/10.3390/ijms25137105
CRediT authorship contribution
Raed Madhi wrote the report and interpreted the findings. The experiments were conducted by Marwah Majeed and Nidhal Abdullah Hashim. Statistical analysis and data visualization were done by Raed Madhi Marwah Majeed and Nidhal Abdullah Hashim. After reading the completed manuscript, each author gave their approval.
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