Biomarkers in Diabetic Foot Disease: Molecular Pathophysiology and Clinical Diagnostic Insights

Diabetic foot disease (DFD) is a common condition caused by diabetes mellitus, and is usually characterized by chronic ulcers, infections and amputations. The illness pathogenesis may involve several factors, including oxidative stress, chronic inflammation, vascular dysfunction and microbial colonization, that may impair tissue healing. DFD is connected with increased death and morbidity and has economic and psychological health implications for individuals. Biomarkers have become powerful tools to link molecular pathophysiology with clinical therapy. Inflammatory biomarkers, including procalcitonin, C-reactive protein, interleukins reflect immune responses, while genomic and proteomic markers, such as PAD4, syndecan-4, and matrix metalloproteinases indicate the changes in cellular and extracellular matrix components. Metabolic markers including glycated hemoglobin, adiponectin and ferritin show systemic metabolic dysregulation, whereas oxidative stress markers such as superoxide dismutase and glutathione indicate redox imbalances related to tissue injury. However, their clinical utility remains variable, and further validation is needed before they can be reliably integrated into routine DFD care. Therefore, this review summarizes the major biomarkers investigated in DFD, focusing on their potential roles in early detection, risk assessment, prognosis, and monitoring disease progression and treatment response. However, in general, the existing evidence indicates that the biomarkers in these various groups may have complimentary functions in the assessment of DFD. In addition, multicenter investigations and standardization are required before their clinical application to DFD can be considered.