Evaluation of Systemic Protein Carbonylation and Glutathione-Dependent Enzymatic Antioxidant Defense Line in Diabetic Foot Syndrome

Abstract

Objective: Diabetic foot syndrome is a debilitating complication of diabetes mellitus closely tied to chronic metabolic dysregulation. This study aimed to evaluate circulating oxidative protein damage and the status of the glutathione-dependent enzymatic antioxidant defense system in patients with diabetic foot syndrome compared to healthy controls. Materials and Methods: In this case-control study, 59 patients diagnosed with diabetic foot syndrome and 63 age-comparable healthy controls were evaluated. Circulating biochemical parameters—protein carbonyl content (PKD) as a marker of oxidative protein modification, and four antioxidant line parameters: glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl/thiol groups (TSH), and glutathione peroxidase (GSHPx)—were assayed. Non-parametric Mann-Whitney U tests, rank-biserial effect sizes, Spearman correlations, receiver operating characteristic (ROC) curves, and principal component analysis (PCA) were conducted. Results: Patients with diabetic foot syndrome demonstrated significantly higher plasma PKD levels compared to controls (median: 5.22 vs. 2.22; p < 0.001). Conversely, all enzymatic antioxidant defense markers were profoundly depleted in diabetic foot patients compared to healthy individuals: GR (1.51 vs. 3.26 U/L), GST (1.18 vs. 2.35 U/L), TSH (2.25 vs. 4.36), and GSHPx (4.82 vs. 8.97; all p < 0.001, effect size r = 1.00). ROC curve analysis demonstrated complete group discrimination (AUC = 1.000 for all parameters). PCA showed that a single primary component capturing composite oxidative balance accounted for 99.5% of the total biochemical variance. Conclusion: Diabetic foot syndrome is characterized by prominent accumulation of oxidative protein damage and concurrent exhaustion of the glutathione-dependent antioxidant capacity. These findings support the systemic oxidative stress paradigm in diabetic complications and highlight the clinical utility of comprehensive redox profiling, though prospective multicenter validation is warranted.