Serum hBD-3 was associated with the presence and severity of diabetic foot infection and provided complementary discriminatory information beyond conventional inflammatory markers, but the combined models remain exploratory and require prospective multicenter external validation before clinical application.
Serum hBD-3 was higher in patients with diabetic foot infection (DFI) than in patients with non-infected diabetic foot disease.
Serum hBD-3 increased with DFI severity.
Higher hBD-3, CRP, PCT and HbA1c and lower albumin were independently associated with prevalent DFI.
The final prevalent-DFI model (HbA1c, albumin, hBD-3, CRP, PCT) showed high discrimination with modest optimism after internal validation.
The moderate/severe DFI model (hBD-3, CRP, PCT) showed high discrimination.
hBD-3 had nonlinear associations with both prevalent DFI and infection severity.
The authors conclude hBD-3 adds discriminatory information beyond conventional inflammatory markers but the models are exploratory.
This study looked at whether a blood level of human β-defensin-3 (hBD-3), a natural antimicrobial protein made by skin and other epithelial cells, could help identify infections in the feet of people with diabetes. Researchers reviewed records of 150 people, including healthy controls, people with diabetes but no foot problems, and people with diabetic foot disease with or without infection. People with diabetic foot infection had higher hBD-3 levels than those with non-infected foot disease, and levels rose with infection severity. When hBD-3 was combined with standard markers like CRP and procalcitonin (plus blood sugar control and albumin for detecting infection), statistical models were quite accurate at distinguishing infected from non-infected cases and moderate/severe from milder infections. Accuracy remained high after internal checks (AUC about 0.90 for infection and 0.92 for moderate/severe infection). This research suggests hBD-3 might be a useful additional marker alongside routine tests. However, the study was small, retrospective, and from limited settings, and the models have not been tested in independent groups. Larger prospective multicenter studies are needed before it could be used in clinical care.
Ma Y, Qu Z, Yao Q, Huang H, Yuan C. (2026). Serum β-defensin-3 and inflammatory markers for discriminating diabetic foot infection and infection severity: a retrospective study.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1966400