Document Type : Original Research Article


1 Medical Laboratory Technology Dept., College of Health and Medical Technology, Southern Technical University, Basrah, Iraq

2 Department of Medical Laboratory Techniques, Al-Nasiriyah Technical Institute, Southern Technical University, Nasiriyah 64001, Iraq

3 Al-Zahra’a Medical College, University of Basrah, Basra, Iraq, Al-Faiha’a Teaching Hospital


Osteomyelitis (OM) is a frequent side effect of diabetic foot infections and/or ulcers. Hemostasis, inflammation, proliferation, remodelling, many cell types, intricate signalling processes, and a variety of growth hormones are all part of the complicated process of wound healing. Therefore, this study's objective is to assess the amounts of procollagen type 1N propeptide for osteomyelitis diagnosis and epithelial neutrophil activator-78 for early wound healing in patients with diabetic foot. This study was included 138 participants (46 patients with the diabetic foot and 52 patients with type 2 diabetes without foot ulcer), their ages ranged from 45-70 years. In addition, healthy people (40) participants were included as a control group. Measurements of lipid profile, blood urea, and creatinine were done by spectrophotometry methods (Spinreact, 2 Spain), whereas measurements concentration of epithelial neutrophil activator-78 (ENA-78) and procollagen type I N-terminal peptide (PINP) were conducted by ELISA methods. This study revealed a highly significant increase of fasting blood glucose (FBG), HbA1c, ENA, and PINP (P<0.01) in type 2 diabetes mellitus and diabetic foot when compared with healthy control and between each other, while other parameters did not show any significant difference. There were marked elevations of serum P1NP & ENA-78 in patients of diabetes only and diabetic foot and they had highly beneficial to diagnosis, risk stratification, and assessment the severity of these diseases.

Graphical Abstract

Evaluation of procollagen 1N propeptide for predicting osteomyelitis and epithelial neutrophil activator-78 for early wound healing in patients with diabetic foot


Main Subjects

[1] M. Shahwan, F. Alhumaydhi, G. M. Ashraf, P. M. Z. Hasan, A. Shamsi, Role of polyphenols in combating type 2 diabetes and insulin resistance, Int. J. Biol. Macromol., 2022, 206,  567-579. [Crossref], [Google Scholar], [Publisher]
[2] S.C. Mishra, K.C. Chhatbar, A. Kashikar, A. Mehndiratta, Diabetic foot, Bmj, 2017, 359, j5064. [Crossref], [Google Scholar], [Publisher]
[3] G. Ouchi, I. Komiya, S. Taira, T. Wakugami, Y. Ohya, Triglyceride/low-density-lipoprotein cholesterol ratio is the most valuable predictor for increased small, dense LDL in type 2 diabetes patients, Lipids Health Dis., 2022, 21, 1–12. [Crossref], [Google Scholar], [Publisher]
[4] R. Malhotra, C.S.Y. Chan, A. Nather, Osteomyelitis in the diabetic foot, Diabet. Foot Ankle, 2014, 5, 24445. [Crossref], [Google Scholar], [Publisher]
[5]          M.J. Gillett, S.D. Vasikaran, C.A. Inderjeeth, The role of PINP in diagnosis and management of metabolic bone disease, Clin. Biochem. Rev., Biochem. Rev., 2021, 42, 3-10. [Crossref], [Google Scholar], [Publisher]
[6] F. Gürdöl, M. Cimsit, Y. Öner-Iyidoğan, H. Koçak, S. Sengun, S. Yalçınkaya-Demirsöz, Collagen synthesis, nitric oxide and asymmetric dimethylarginine in diabetic subjects undergoing hyperbaric oxygen therapy, Physiol. Res., 2010, 59, 423-429. [Crossref], [Google Scholar], [Publisher]
[7]          J.L. Burgess, W.A. Wyant, B. Abdo Abujamra, R.S. Kirsner, I. Jozic, Diabetic wound-healing science, Medicina (B. Aires), 2021, 57, 1072. [Crossref], [Google Scholar], [Publisher]
[8] J. Li, Z. Wang, A. Deng, Y. Li, ENA-78 is a novel predictor of wound healing in patients with diabetic foot ulcers, J. Diabetes Res., 2019, 2019, Article ID 2695436. [Crossref], [Google Scholar], [Publisher]
[9] E. Lerchbaum, V. Schwetz, M. Nauck, H. Völzke, H. Wallaschofski, A. Hannemann, Lower bone turnover markers in metabolic syndrome and diabetes: the population-based Study of Health in Pomerania, Nutr. Metab. Cardiovasc. Dis., 2015, 25, 458–463. [Crossref], [Google Scholar], [Publisher]
[10] A.L. Beitelshees, Christina L. Aquilante, H. Allayee, T.Y. Langaee, G.J. Welder, R.S. Schofield, I. Zineh,  CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults, Hum. Genomics, 2012, 6, 1–8. [Crossref], [Google Scholar], [Publisher]
[11] R.A. Farris, E.T. Price, Reverse translational study of fenofibrate’s observed effects in diabetes‐associated retinopathy, Clin. Transl. Sci., 2017, 10, 110–116. [Crossref], [Google Scholar], [Publisher]
[12] P.J. Mishra, P.J. Mishra, D. Banerjee, Cell-free derivatives from mesenchymal stem cells are effective in wound therapy, World J. Stem Cells, 2012, 4, 35-43. [Crossref], [Google Scholar], [Publisher]
[13] F. Bragg, M.V. Holmes, A. Iona, Y. Guo, H. Du, Y. Chen, Z. Bian, L. Yang, W. Herrington, D. Bennett, I. Turnbull, Y. Liu, S. Feng, J. Chen, R. Clarke, R. Collins, R. Peto, L. Li, Z. Chen, Association between diabetes and cause-specific mortality in rural and urban areas of China, Jama, 2017, 317, 280–289. [Crossref], [Google Scholar], [Publisher]
[14] N.K. Chammas, R.L.R. Hill, M.E. Edmonds, Increased mortality in diabetic foot ulcer patients: the significance of ulcer type, J. Diabetes Res., 2016, 2016, Article ID 2879809. [Crossref], [Google Scholar], [Publisher]
[15] N. Singh, D.G. Armstrong, B.A. Lipsky, Preventing foot ulcers in patients with diabetes, Jama, 2005, 293, 217–228. [Crossref], [Google Scholar], [Publisher]
[16] R.A. Speckman, D.L. Frankenfield, S.H. Roman, P.W. Eggers, M.R. Bedinger, M.V. Rocco, W.M. McClellan, Diabetes is the strongest risk factor for lower-extremity amputation in new hemodialysis patients, Diabetes Care, 2004, 27, 2198–2203. [Crossref], [Google Scholar], [Publisher]
[17] S. Yin, P. Zhao, Z. Ai, B. Deng, W. Jia, H. Wang, J. Zheng, Sex‐specific differences in blood lipids and lipid ratios in type 2 diabetic foot patients,  J. Diabetes Investig., 2021, 12, 2203–2211. [Crossref], [Google Scholar], [Publisher]
[18] W. Luther, H. Eickenbusch, O. S. Kaiser, L. Brand, Application of nanotechnologies in the energy sector. Hessen Trade & Invest GmbH, 2015. [Crossref], [Google Scholar]
[19] G.C. Gurtner, S. Werner, Y. Barrandon, M.T. Longaker, Wound repair and regeneration, Nature, 2008, 453, 314–321. [Crossref], [Google Scholar], [Publisher]
[20] J.L. Hudgens, K.B. Sugg, J.A. Grekin, J.P. Gumucio, A. Bedi, C.L. Mendias, Platelet-rich plasma activates proinflammatory signaling pathways and induces oxidative stress in tendon fibroblasts,  Am. J. Sports Med., 2016, 44, 1931–1940. [Crossref], [Google Scholar], [Publisher]
[21] C. Nathan, Neutrophils and immunity: challenges and opportunities, Nat. Rev. Immunol., 2006, 6, 173–182. [Crossref], [Google Scholar], [Publisher]
[22] G.A. Mostafa, L.Y. Al-Ayadhi, The possible link between elevated serum levels of epithelial cell-derived neutrophil-activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children, Behav. Brain Funct., 2015, 11, 1–7. [Crossref], [Google Scholar], [Publisher]
[23] O.G. Hayes, V.N. Vangaveti, U.H. Malabu, Serum procollagen type 1 N propeptide: A novel diagnostic test for diabetic foot osteomyelitis–A case–control study, J. Res. Med. Sci., 2018, 23, PMC5996568. [Crossref], [Google Scholar], [Publisher]
[24] J.M. Cancienne, B.C. Werner, J.A. Browne, Is there a threshold value of hemoglobin A1c that predicts risk of infection following primary total hip arthroplasty, J. Arthroplasty, 2017, 32, S236–S240. [Crossref], [Google Scholar], [Publisher]
[25] G. Casadei, M. Filippini, L. Brognara, Glycated hemoglobin (HbA1c) as a biomarker for diabetic foot peripheral neuropathy, Diseases, 2021, 9, 16. [Crossref], [Google Scholar], [Publisher]
[26] Z. Ghazanfari, A.A. Haghdoost, S.M. Alizadeh, J. Atapour, F. Zolala, A comparison of HbA1c and fasting blood sugar tests in general population, Int. J. Prev. Med., 2010, 1, 187. [Crossref], [Google Scholar], [Publisher]
[27] J.M.P. D’souza, R.P. D’souza, V.F. Vijin, A. Shetty, C. Arunachalam, V.R. Pai, R. Shetty, A. Faarisa, High predictive ability of glycated hemoglobin on comparison with oxidative stress markers in assessment of chronic vascular complications in type 2 diabetes mellitus, Scand. J.  Clin. Lab. Invest., 2016, 76, 51–57. [Crossref], [Google Scholar], [Publisher]
[28] S. Hasani Ranjbar, P. Amiri, I. Zineh, T.Y. Langaee, M. Namakchian, R. Heshmet, M. Sajadi, M. Mirzaee, E. Rezazadeh, P. Balaei, J. Tavakkoly Bazzaz, M.A. Gonzalez-Gay, B. Larijani, M.M. Amoli, CXCL5 gene polymorphism association with diabetes mellitus,  Mol. Diagnosis Ther., 2008, 12, 391–394. [Crossref], [Google Scholar], [Publisher]  
[29] D.A. Lebedev, E.A. Lyasnikova, A.A. Vasilyeva, E.Y. Vasilyeva, A.Y. Babenko, E.V. Shlyakhto, Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes,  Russ. J. Cardiol., 2020, 25, 70–78. [Crossref], [Google Scholar], [Publisher]