KALLISTATIN AS A POTENTIAL BIOMARKER FOR EVALUATING THERAPEUTIC EFFICACY OF ALPHA LIPOIC ACID IN DIABETIC PATIENTS WITH SENSORIMOTOR POLYNEUROPATHY

Abstract

Introduction: Diabetic sensorimotor neuropathy (DSPN) is closely linked to cellular oxidative stress and endothelial dysfunction in type 2 diabetes (T2DM). Alpha-lipoic acid (ALA) mitigates DSPN progression through its antioxidant and vasculoprotective properties. Kallistatin, a protein with antioxidant and anti-inflammatory functions, may play a role in these mechanisms. Aim: This study aimed to assess changes in kallistatin levels and endothelial dysfunction markers in patients with T2DM and DSPN after six months of treatment with 600 mg/day of ALA. Patients and methods: Fifty-four patients with T2DM and DSPN and 24 controls with T2DM but no neuropathy were enrolled. Serum levels of kallistatin, ICAM-1, VCAM-1, oxLDL, VEGF, ADMA, and TNF-α were quantified using ELISA. Peripheral sensory neuropathy was evaluated via neuropathy symptom questionnaires and current perception threshold measurements. Results: Following six months of ALA therapy, kallistatin levels demonstrated a positive correlation with serum ICAM-1 (r=0.31, p=0.031) and TNF-α (r=0.45, p=0.001) levels, while an inverse relationship was observed with NO levels (r=-0.4, p=0.017). Among DSPN patients, changes in kallistatin concentrations were positively associated with changes in oxLDL levels (r=0.33, p=0.02). Additionally, a significant correlation was identified between changes in VEGF and oxLDL levels post-treatment (r=0.29, p=0.04). Improvement in NTSS-6 scores, reflecting neuropathy symptoms, was positively correlated with changes in kallistatin (r=0.37, p=0.008), VEGF (r=0.45, p=0.001), oxLDL (r=0.51, p<0.001), and ADMA levels (r=0.28, p=0.038). Conclusion: These findings suggest that kallistatin may serve as a novel biomarker for monitoring therapeutic responses to ALA in patients with DSPN, offering potential insights into disease progression and treatment efficacy.