[The Relationship Between HIF-1α, MMP-9, and IL-8 Levels and the Development of Diabetic Foot Ulcers]

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, leading to high morbidity and mortality rates. Early diagnosis of DFUs is critical for improving patients’ quality of life and reducing the burden on healthcare systems. This study aimed to identify biomarkers that can predict the early development of DFUs and evaluate their potential for clinical applications. The study included three groups: diabetic patients with DFUs, diabetic patients without ulcers and healthy individuals. Serum levels of hypoxia-inducible factor-1 alpha (HIF-1α), matrix metallopeptidase 9 (MMP-9) and IL-8 were measured in blood samples and these biomarkers were compared with acute phase reactants such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and procalcitonin. The diagnostic values of these biomarkers were assessed using receiver operating characteristic (ROC) analysis. HIF-1α levels were found to be significantly elevated in patients with DFUs and ROC analysis revealed that this biomarker had the highest diagnostic sensitivity and specificity [area the under curve (AUC= 0.99, p= 0.001)]. The increase in HIF-1α levels suggested that hypoxic responses remain active during the early stages of DFU but decrease in advanced stages due to impaired tissue response to hypoxia. MMP-9 levels were observed to increase proportionally with Wagner stages and were positively correlated with ESR, indicating its role in chronic inflammation and tissue damage. IL-8 levels were significantly elevated in DFU patients, yet their lack of correlation with other inflammatory markers suggested that IL-8 might have a more specific role in the inflammatory process. HIF-1α emerges as a key biomarker in the early detection of DFUs due to its central role in hypoxia-driven tissue repair and angiogenesis. Owing to its high specificity and sensitivity (AUC= 0.99), it should be considered a promising biomarker for routine clinical monitoring. The role of MMP-9 in chronic inflammation and tissue degradation suggests that this biomarker may contribute to the development of therapies aimed at preventing tissue damage. Similarly, the role of IL-8 in specific inflammatory processes may lead to the development of novel therapeutic approaches targeting neutrophil modulation. Regular monitoring of HIF-1α, MMP-9, and IL-8 could facilitate the early diagnosis and prevention of DFUs. Additionally, the clinical application of these biomarkers may improve patient quality of life while reducing the economic burden on healthcare systems. Future prospective studies may provide more robust evidence to support the widespread clinical use of these biomarkers.