SpringerLink
Log in

Effects of diabetic foot infection on vascular and immune function in the lower limbs

  • Original Article
  • Published:
International Journal of Diabetes in Develo** Countries Aims and scope Submit manuscript

Abstract

Object

The study investigated the effects of diabetic foot infection on vascular and immune function in the lower limbs.

Methods

Seventy-two patients with diabetic foot infection were included in the infected group, while 64 diabetic patients without infection were selected as the control group. Hemodynamic parameters and vascular endothelial function of the dorsalis pedis artery were assessed by color Doppler ultrasonography. Enzyme-linked immunosorbent assay was used to determine the serum levels of interleukin 6 (IL-6), IL-17, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and high mobility group box 1 protein (HMGB1). Western blotting was used to quantify expression levels of toll-like receptor 4 (TLR4) and nuclear transcription factor kappa B (NFκB) in human peripheral blood mononuclear cells (PBMC).

Results

Compared with the control group, the intima-media thickness and peak systolic velocity of the infected group were increased (both p < 0.05), while the inner vascular diameter, blood flow volume, endothelium-dependent dilation, and endothelium-independent dilation were decreased (all p < 0.05). Compared with the control group, the serum levels of IL-6, IL-17, TNF-α, CRP, and HMGB1, and the expression levels of TLR4 and NFκB in PBMC were significantly increased in the infected group (all p < 0.001).

Conclusion

Thus, diabetic foot infection is associated with vascular and immune dysfunction in the lower limbs, possibly in relation to the activation of the HMGB1/TLR4/NFκB signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. d’Emden MC, Shaw JE, Jones GR, Cheung NW. Guidance concerning the use of glycated haemoglobin (HbA1c) for the diagnosis of diabetes mellitus. Med J Aust. 2015;203(2):89–90.

    Article  PubMed  Google Scholar 

  2. Kulprachakarn K, Ounjaijean S, Wungrath J, Mani R, Rerkasem K. Micronutrients and natural compounds status and their effects on wound healing in the diabetic foot ulcer. Int J Low Extrem Wounds. 2017;16(4):244–50.

    Article  PubMed  Google Scholar 

  3. Thurber EG, Kisuule F, Humbyrd C, Townsend J. Inpatient management of diabetic foot infections: a review of the guidelines for hospitalists. J Hosp Med. 2017;12(12):994–1000.

    Article  PubMed  Google Scholar 

  4. Zhao WN, Xu SQ, Liang JF, Peng L, Liu HL, Wang Z, et al. Endothelial progenitor cells from human fetal aorta cure diabetic foot in a rat model. Metabolism. 2016;65(12):1755–67.

    Article  CAS  PubMed  Google Scholar 

  5. Jhamb S, Vangaveti VN, Malabu UH. Genetic and molecular basis of diabetic foot ulcers: clinical review. J Tissue Viability. 2016;25(4):229–36.

    Article  PubMed  Google Scholar 

  6. Lipsky BA, Silverman MH, Joseph WS. A proposed new classification of skin and soft tissue infections modeled on the subset of diabetic foot infection. Open Forum Infect Dis. 2017;4(1):ofw255.

  7. Chen SY, Giurini JM, Karchmer AW. Invasive systemic infection after hospital treatment for diabetic foot ulcer: risk of occurrence and effect on survival. Clin Infect Dis. 2017;64(3):326–34.

    Article  PubMed  Google Scholar 

  8. Hafez YM, El-Deeb OS, Atef MM. The emerging role of the epigenetic enzyme Sirtuin-1 and high mobility group Box 1 in patients with diabetic foot ulceration. Diabetes Metab Syndr. 2018;12(6):1065–70.

    Article  PubMed  Google Scholar 

  9. Sun J, Shi S, Wang Q, Yu K, Wang R. Continuous hemodiafiltration therapy reduces damage of multi-organs by ameliorating of HMGB1/TLR4/NFκB in a dog sepsis model. Int J Clin Exp Pathol. 2015;8(2):1555–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG, et al. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. J Am Podiatr Med Assoc. 2013;103(1):2–7.

    Article  PubMed  Google Scholar 

  11. Celermajer DS, Sorensen KE, Gooch VM. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosiz. Lancet. 1992;340(8828):1111–5.

    Article  CAS  PubMed  Google Scholar 

  12. Guan D, Mi J, Chen X, Wu Y, Yao Y, Wang L, et al. Lung endothelial cell-targeted peptide-guided bFGF promotes the regeneration after radiation induced lung injury. Biomaterials. 2018;184:10–9.

    Article  CAS  PubMed  Google Scholar 

  13. Gao J, Zhao G, Li W, Zhang J, Che Y, Song M, et al. MiR-155 targets PTCH1 to mediate endothelial progenitor cell dysfunction caused by high glucose. Exp Cell Res. 2018;366(1):55–62.

    Article  CAS  PubMed  Google Scholar 

  14. Li X, **e X, Lian W, Shi R, Han S, Zhang H, et al. Exosomes from adipose-derived stem cells overexpressing Nrf2 accelerate cutaneous wound healing by promoting vascularization in a diabetic foot ulcer rat model. Exp Mol Med. 2018;50(4):29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. You J, Sun J, Ma T, Yang Z, Wang X, Zhang Z, et al. Curcumin induces therapeutic angiogenesis in a diabetic mouse hindlimb ischemia model via modulating the function of endothelial progenitor cells. Stem Cell Res Ther. 2017;8(1):182.

    Article  PubMed  PubMed Central  Google Scholar 

  16. **ng Y, Lai J, Liu X, Zhang N, Ming J, Liu H, et al. Netrin-1 restores cell injury and impaired angiogenesis in vascular endothelial cells upon high glucose by PI3K/AKT-eNOS. J Mol Endocrinol. 2017;58(4):167–77.

    Article  CAS  PubMed  Google Scholar 

  17. Baluk P, Phillips K, Yao LC, Adams A, Nitschké M, McDonald DM. Neutrophil dependence of vascular remodeling after mycoplasma infection of mouse airways. Am J Pathol. 2014;184(6):1877–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Almodovar S, Swanson J, Giavedoni LD, Kanthaswamy S, Long CS, Voelkel NF, et al. Lung vascular remodeling, cardiac hypertrophy, and inflammatory cytokines in SHIVnef-infected macaques. Viral Immunol. 2018;31(3):206–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One. 2010;5:e9539.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Fu Y, Lei J, Zhuang Y, Zhang K, Lu D. Overexpression of HMGB1 A-box reduced IL-1β-induced MMP expression and the production of inflammatory mediators in human chondrocytes. Exp Cell Res. 2016;349(1):184–90.

    Article  CAS  PubMed  Google Scholar 

  21. He L, Sun F, Wang Y, Zhu J, Fang J, Zhang S, et al. HMGB1 exacerbates bronchiolitis obliterans syndrome via RAGE/NF-κB/HPSE signaling to enhance latent TGF-β release from ECM. Am J Transl Res. 2016;8(5):1971–84.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Rojas A, Delgado-López F, Perez-Castro R, Gonzalez I, Romero J, Rojas I, et al. HMGB1 enhances the protumoral activities of M2 macrophages by a RAGE-dependent mechanism. Tumour Biol. 2016;37(3):3321–9.

    Article  CAS  PubMed  Google Scholar 

  23. Yan XX, Lu L, Peng WH, Wang LJ, Zhang Q, Zhang RY, et al. Increased serum HMGB1 level is associated with coronary artery disease in nondiabetic and type 2 diabetic patients. Atherosclerosis. 2009;205(2):544–8.

    Article  CAS  PubMed  Google Scholar 

  24. Yang J, Chen L, Ding J, Fan Z, Li S, Wu H, et al. MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1. Gene. 2016;586(2):268–73.

    Article  CAS  PubMed  Google Scholar 

  25. Elfeky M, Kaede R, Okamatsu-Ogura Y, Kimura K. Adiponectin inhibits LPS-induced HMGB1 release through an AMP kinase and heme oxygenase-1-dependent pathway in RAW 264 macrophage cells. Mediat Inflamm. 2016;2016:1–9.

    Article  Google Scholar 

  26. Meng L, Li L, Lu S, Li K, Su Z, Wang Y, et al. The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways. Mol Immunol. 2018;94:7–17.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, The First People’s Hospital of Wujiang District of Suzhou, No.196 Park Road, Wujiang District, Suzhou, 215000, Jiangsu Province, China

    **aohua Shen, Meixiang Zhang, Xuehua Jiao, **aofeng Cang & Ye Lu

Authors
  1. **aohua Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meixiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuehua Jiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. **aofeng Cang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ye Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to **aohua Shen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, X., Zhang, M., Jiao, X. et al. Effects of diabetic foot infection on vascular and immune function in the lower limbs. Int J Diabetes Dev Ctries 39, 673–679 (2019). https://doi.org/10.1007/s13410-019-00750-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-019-00750-1

Keywords

Search

Navigation