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Peer-reviewedCC BY 4.0Frontiers in Endocrinology

Serum β-defensin-3 and inflammatory markers for discriminating diabetic foot infection and infection severity: a retrospective study

4 affiliations
  1. 1School of Basic Medical Sciences, China Three Gorges University
  2. 2Clinical Laboratory, Yuan’an People’s Hospital
  3. 3School of Health Medicine, China Three Gorges University
  4. 4Department of Burns, Yichang Central People’s Hospital

Abstract

Background: Human β-defensin-3 (hBD-3) is an epithelial-derived antimicrobial peptide involved in innate immunity and tissue repair, but its clinical association with diabetic foot infection (DFI) remains insufficiently characterized.

Objective: To evaluate the associations of serum hBD-3 with prevalent DFI and infection severity and to assess its discriminatory performance alone and in combination with conventional inflammatory markers.

Methods: This retrospective study included 150 participants: 30 healthy controls, 30 patients with diabetes without foot disease, and 90 patients with diabetic foot disease, including 30 without infection and 60 with DFI. Logistic regression and LASSO penalized regression were used to identify factors associated with prevalent DFI and moderate/severe infection. Restricted cubic spline analyses explored nonlinear associations. Discriminatory performance was evaluated using receiver operating characteristic curves, and internal validation was performed with 1,000 bootstrap resamples.

Results: Serum hBD-3 was higher in patients with DFI than in those with non-infected diabetic foot disease [108.9 (86.3, 141.5) vs. 69.8 (56.1, 84.7) pg/mL, P < 0.001] and increased with infection severity. Higher hBD-3, CRP, PCT, and HbA1c and lower albumin were independently associated with prevalent DFI. The final prevalent-DFI model included HbA1c, albumin, hBD-3, CRP, and PCT and achieved an apparent AUC of 0.928, with an optimism-corrected AUC of 0.895. The moderate/severe DFI model included hBD-3, CRP, and PCT and achieved an apparent AUC of 0.935 and an optimism-corrected AUC of 0.917. RCS analyses suggested nonlinear associations between hBD-3 and both prevalent DFI and infection severity.

Conclusion: Serum hBD-3 was associated with the presence and severity of DFI and provided complementary discriminatory information beyond conventional inflammatory markers. The combined models showed promising performance but remain exploratory and require prospective multicenter external validation before clinical application.

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BibTeX
@article{ma2026serum,
  title = {{Serum β-defensin-3 and inflammatory markers for discriminating diabetic foot infection and infection severity: a retrospective study}},
  author = {Yali Ma and Zhao Qu and Qianqian Yao and Huimin Huang and Chengfu Yuan},
  journal = {Frontiers in Endocrinology},
  year = {2026},
  month = oct,
  doi = {10.3389/fendo.2026.1966400},
  url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1966400/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Serum β-defensin-3 and inflammatory markers for discriminating diabetic foot infection and infection severity: a retrospective study
AU  - Yali Ma
AU  - Zhao Qu
AU  - Qianqian Yao
AU  - Huimin Huang
AU  - Chengfu Yuan
PY  - 2026
DA  - 2026/10/14
JO  - Frontiers in Endocrinology
DO  - 10.3389/fendo.2026.1966400
UR  - https://www.frontiersin.org/articles/10.3389/fendo.2026.1966400/full
AB  - Background: Human β-defensin-3 (hBD-3) is an epithelial-derived antimicrobial peptide involved in innate immunity and tissue repair, but its clinical association with diabetic foot infection (DFI) remains insufficiently characterized.  Objective: To evaluate the associations of serum hBD-3 with prevalent DFI and infection severity and to assess its discriminatory performance alone and in combination with conventional inflammatory markers.  Methods: This retrospective study included 150 participants: 30 healthy controls, 30 patients with diabetes without foot disease, and 90 patients with diabetic foot disease, including 30 without infection and 60 with DFI. Logistic regression and LASSO penalized regression were used to identify factors associated with prevalent DFI and moderate/severe infection. Restricted cubic spline analyses explored nonlinear associations. Discriminatory performance was evaluated using receiver operating characteristic curves, and internal validation was performed with 1,000 bootstrap resamples.  Results: Serum hBD-3 was higher in patients with DFI than in those with non-infected diabetic foot disease [108.9 (86.3, 141.5) vs. 69.8 (56.1, 84.7) pg/mL, P < 0.001] and increased with infection severity. Higher hBD-3, CRP, PCT, and HbA1c and lower albumin were independently associated with prevalent DFI. The final prevalent-DFI model included HbA1c, albumin, hBD-3, CRP, and PCT and achieved an apparent AUC of 0.928, with an optimism-corrected AUC of 0.895. The moderate/severe DFI model included hBD-3, CRP, and PCT and achieved an apparent AUC of 0.935 and an optimism-corrected AUC of 0.917. RCS analyses suggested nonlinear associations between hBD-3 and both prevalent DFI and infection severity.  Conclusion: Serum hBD-3 was associated with the presence and severity of DFI and provided complementary discriminatory information beyond conventional inflammatory markers. The combined models showed promising performance but remain exploratory and require prospective multicenter external validation before clinical application.
SN  - 1664-2392
ER  -