Background. Diabetic foot syndrome (DFS) is one of the most severe complications of type 2 diabetes mellitus (T2DM), developing through a complex interaction of chronic hyperglycemia, insulin resistance, endothelial activation, adipokine imbalance, impaired tissue remodeling and persistent inflammation. Identification of clinically meaningful biomarkers may improve early risk assessment and prevention of severe trophic complications.
Objective. To evaluate the contribution of clinical, metabolic and immunometabolic factors to the development of DFS in patients with T2DM and to develop a predictive model for risk stratification.
Materials and methods. The study included patients with T2DM with and without DFS, as well as a control group of conditionally healthy individuals. Clinical and laboratory parameters, indices of carbohydrate and lipid metabolism, insulin resistance, adipokine status, endothelial activation and extracellular matrix remodeling were analyzed. Logistic regression analysis was used to identify predictors associated with DFS. ROC analysis was performed to assess the diagnostic value of selected biomarkers. The most informative predictors were integrated into the BGU database-based immunometabolic risk model.
Results. Univariate regression analysis showed that body mass index, arterial hypertension, HbA1c, fasting glucose, HOMA-IR, lipid profile parameters, leptin, adiponectin, VEGF-A, IGF-1, TGF-β1, sVCAM-1 and MMP-9 were associated with DFS risk. In multivariate analysis, five independent predictors retained statistical significance: HbA1c, HOMA-IR, adiponectin, sVCAM-1 and MMP-9. ROC analysis demonstrated the highest diagnostic performance for MMP-9, with an AUC of 0.993, cut-off value of 258.9 ng/mL, sensitivity of 92.9% and specificity of 100.0%. Adiponectin and sVCAM-1 also showed clinically relevant diagnostic value. Based on these findings, an integrated model was developed to classify patients into low, moderate and high DFS risk categories.
Conclusion. DFS in T2DM is associated not with a single isolated factor, but with a combined pattern of chronic hyperglycemia, insulin resistance, reduced protective adipokine activity, endothelial activation and matrix destruction. The proposed immunometabolic model may support early identification of high-risk patients and improve personalized prevention of diabetic foot complications.