ASSOCIATION OF MOLECULAR BIOMARKERS WITH DISEASE SEVERITY IN DIABETIC FOOT ULCERS: A CASE CONTROL STUDY

Abstract

Introduction: Diabetic foot ulcers (DFUs) represent one of the most serious chronic complications of diabetes mellitus and are a major cause of increased morbidity, recurrent hospital admissions, and lower-limb amputations. Persistent inflammation plays a central role in the development and progression of DFUs. Identifying inflammatory molecular biomarkers associated with ulcer severity may facilitate early diagnosis, prognostic assessment, and improved clinical management. Aim: To determine the serum levels of the inflammatory biomarkers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) in diabetic patients with and without foot ulcers, and to investigate their association with disease severity across different Wagner grades of diabetic foot ulcers. Methods: A hospital-based case-control study was conducted involving 250 participants, including 125 patients with diabetic foot ulcers and 125 diabetic patients without foot ulcers. Demographic, clinical, and biochemical characteristics were retrieved from electronic medical records. Diabetic foot ulcers were graded using the Wagner classification system. Serum TNF-α, IL-6, and hs-CRP levels were quantified using enzyme-linked immunosorbent assay (ELISA). Comparative statistical analyses were performed between groups, and correlations between biomarker levels and Wagner grades were evaluated. Results: Serum TNF-α, IL-6, and hs-CRP concentrations were significantly higher in patients with diabetic foot ulcers than in diabetic controls without foot ulcers (P < 0.001). Moreover, the levels of all three inflammatory biomarkers showed a significant stepwise increase with increasing Wagner grades. Positive correlations were observed between biomarker concentrations and ulcer severity (P < 0.001), suggesting that systemic inflammation intensifies with disease progression. Conclusion: Elevated serum TNF-α, IL-6, and hs-CRP levels are strongly associated with increasing severity of diabetic foot ulcers. These inflammatory biomarkers may serve as useful adjunctive indicators for disease severity assessment, risk stratification, and individualized management of patients with diabetic foot ulcers.