Integrative Predictive and Prognostic Value of Novel Biomarkers in Diabetic Foot Complications

Abstract

Background: Diabetic foot ulcers (DFU) are devastating complications with high rates of morbidity, amputation, and mortality. Traditional inflammatory markers are not specific in discriminating localized inflammation from the severity of systemic inflammation, and novel biomarkers are required for adequate risk stratification. Objective: This study   aimed to assess the combined predictive and prognostic value of presepsin, mid-regional pro-adrenomedullin (MR-proADM), and endocan in evaluating DFU severity and predicting poor clinical outcomes. Materials and Methods: A total of 120 patients with DFU were enrolled in a prospective observational study and stratified according to the Wagner grade (0-5). Serum presepsin, MR-proADM, endocan, and conventional inflammatory parameters were determined at the time of admission. Clinical outcomes (healing, chronic wounds, amputation, and mortality) were followed. Results: Novel  biomarkers were significantly and progressively elevated with increasing severity of the Wagner grade (p < 0.001). Patients with adverse events (major amputation, death) had remarkably elevated levels of presepsin, MR-proADM, and endocan compared with those with completely healed wounds. All three biomarkers were strongly associated with the Wagner grade and classical markers (p < 0.001). ROC analysis showed excellent discriminatory ability (AUC > 0.91), resulting in a combined biomarker score with a predictive value of AUC = 0.923. Univariate logistic regression showed that MR-proADM (OR = 7.  331), endocan (OR = 2. Conclusions: Presepsin, MR-proADM, and endocan are powerful and independent predictive markers of DFU. Their continuous increase parallels tissue damage and systemic decompensation, and they have better predictive power for adverse outcomes than traditional markers.