Investigating serum NRF2 as a screening biomarker and potential therapeutic target in diabetic foot ulcers: a prospective observational study.

Objectives: The study aimed to investigate the relationship between serum nuclear factor erythroid 2-related factor 2 (NRF2) levels and the severity of diabetic foot ulcers (DFU) and to identify potential risk factors in severe DFU patients. Understanding this relationship could offer insights into mechanisms underlying DFU progression and inform diagnostic and therapeutic strategies.

Methods: This prospective observational study included 195 DFU patients from January 2023 to May 2024, categorized into mild and severe groups using the Wagner classification system. Serum NRF2 and C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-alpha (TNF-α) levels were measured at multiple timepoints during treatment. Statistical analyses, including logistic regression and receiver operating characteristic (ROC) curve analysis, were performed to evaluate NRF2's diagnostic value and its association with DFU severity.

Results: We found that severe DFU patients had significantly lower serum NRF2 levels and higher serum IL-6, IL-17, and CRP levels compared to those in the mild group. NRF2 levels were negatively correlated with IL-6 levels. ROC curve analysis demonstrated that NRF2 was a reliable screening biomarker for severe DFU, with notable sensitivity and specificity. In addition, logistic regression identified reduced NRF2 levels as an independent risk factor for severe DFU.

Conclusions: Serum NRF2 levels could serve as a valuable screening biomarker for identifying severe DFU cases. Integrating NRF2 measurements with other biomarkers could improve patient stratification and clinical outcomes. Further research is needed to validate its role and therapeutic potential in DFU management.