Hernyák Marcell, Tóth László Imre, Csiha Sára, Molnár Ágnes, Lőrincz Hajnalka, Paragh György, Harangi Mariann, Sztanek Ferenc
Division of Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Doctoral School of Health Sciences, University of Debrecen, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2024 Dec 11;25(24):13276. doi: 10.3390/ijms252413276.
Diabetic sensorimotor neuropathy (DSPN) is strongly associated with the extent of cellular oxidative stress and endothelial dysfunction in type 2 diabetes (T2DM). Alpha-lipoic acid (ALA) attenuates the progression of DSPN through its antioxidant and vasculoprotective effects. Kallistatin has antioxidant and anti-inflammatory properties. We aimed to evaluate changes in kallistatin levels and markers of endothelial dysfunction in patients with T2DM and DSPN following six months of treatment with 600 mg/day of ALA. A total of 54 patients with T2DM and DSPN and 24 control patients with T2DM but without neuropathy participated in this study. The serum concentrations of kallistatin, ICAM-1, VCAM-1, oxLDL, VEGF, ADMA, and TNF-alpha were measured by an ELISA. Peripheral sensory neuropathy was assessed with neuropathy symptom questionnaires and determination of the current perception threshold. After ALA treatment, the level of kallistatin significantly decreased, as well as the levels of TNF-alpha and ADMA. Changes in kallistatin levels were positively correlated with changes in oxLDL. The improvement in DSPN symptoms following ALA treatment showed a positive correlation with changes in kallistatin, VEGF, oxLDL, and ADMA levels. Based on our results, kallistatin could represent a potential new biomarker for assessing therapeutic response during ALA treatment in patients with DSPN.
糖尿病性感觉运动神经病变（DSPN）与2型糖尿病（T2DM）患者的细胞氧化应激程度和内皮功能障碍密切相关。α-硫辛酸（ALA）通过其抗氧化和血管保护作用减缓DSPN的进展。激肽释放酶原具有抗氧化和抗炎特性。我们旨在评估2型糖尿病合并DSPN患者在接受600毫克/天ALA治疗6个月后激肽释放酶原水平的变化以及内皮功能障碍标志物的变化。共有54例2型糖尿病合并DSPN患者和24例2型糖尿病但无神经病变的对照患者参与了本研究。采用酶联免疫吸附测定法（ELISA）检测血清中激肽释放酶原、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）、氧化型低密度脂蛋白（oxLDL）、血管内皮生长因子（VEGF）、不对称二甲基精氨酸（ADMA）和肿瘤坏死因子-α（TNF-α）的浓度。通过神经病变症状问卷和电流感觉阈值测定评估周围感觉神经病变。ALA治疗后，激肽释放酶原水平以及TNF-α和ADMA水平显著降低。激肽释放酶原水平的变化与oxLDL的变化呈正相关。ALA治疗后DSPN症状的改善与激肽释放酶原、VEGF、oxLDL和ADMA水平的变化呈正相关。根据我们的研究结果，激肽释放酶原可能是评估DSPN患者ALA治疗期间治疗反应的一种潜在新生物标志物。
