Pingali Usharani, Kammila Sireesha, Mekala Padmaja, Yareeda Sireesha, Penugonda Sravanasandya
Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, IND.
Neurology, Nizam's Institute of Medical Sciences, Hyderabad, IND.
Cureus. 2024 Sep 27;16(9):e70299. doi: 10.7759/cureus.70299. eCollection 2024 Sep.
Introduction Chronic hyperglycemia is a key factor in the development of diabetic peripheral neuropathy (DPN), contributing significantly to the progression of this condition through the induction of oxidative stress. Elevated blood glucose levels lead to increased production of reactive oxygen species (ROS), which cause damage to neuronal cells and exacerbate neuropathic symptoms. Alpha-lipoic acid (ALA) is a potent antioxidant that neutralizes ROS and reduces oxidative damage. By addressing the mechanisms of neuropathy, ALA mitigates the effects of chronic hyperglycemia through antioxidant regeneration, inflammation reduction, and endothelial function improvement. As a result, ALA is emerging as a promising intervention for managing oxidative stress and inflammation in DPN. Methods Prospective, double-blind, placebo-controlled study, a total of 52 DPN subjects on gabapentin or pregabalin were randomly assigned to either ALA 600 mg oral once daily or placebo oral once daily for 12 weeks. Treatment outcome was assessed using vibration perception threshold (VPT), Neuropathy Total Symptom Score 6 (NTSS-6), quality of life (QOL) assessed by 12-Item Short Form Health Survey (SF-12) Questionnaire, oxidative stress biomarkers (malondialdehyde (MDA), nitric oxide (NO), and glutathione (GSH)) and inflammatory biomarker (high-sensitivity C-reactive protein (hs-CRP)) at baseline and every visit (four, eight, and 12 weeks). Neuron-specific enolase (NSE) levels were done at baseline and 12 weeks. Glycated hemoglobin (HbA1C) and safety parameters were done at screening and 12 weeks. Compliance with the study medication was assessed by pill count. Reported adverse drug reactions were recorded. Results A total of 52 subjects (males = 22; females = 30) with a mean age of 55.63 ± 7.5 years were randomized to receive either ALA or placebo. A significant reduction in VPT was observed with ALA at 12 weeks compared to baseline (from 26.92 ± 3.58 to 22.14 ± 1.94; p < 0.0001). Secondary parameters like NTSS-6, QOL by SF-12 questionnaire, NSE levels, oxidative biomarkers levels, and inflammatory biomarkers showed significant improvement with ALA compared to placebo. No serious adverse events were reported. Conclusion ALA demonstrated a protective effect against DPN by its antioxidant and anti-inflammatory effects and was found to have good safety.
引言 慢性高血糖是糖尿病周围神经病变（DPN）发展的关键因素，通过诱导氧化应激对该病症的进展有显著影响。血糖水平升高导致活性氧（ROS）生成增加，从而损害神经元细胞并加重神经病变症状。α-硫辛酸（ALA）是一种有效的抗氧化剂，可中和ROS并减少氧化损伤。通过解决神经病变的机制，ALA通过抗氧化剂再生、减轻炎症和改善内皮功能来减轻慢性高血糖的影响。因此，ALA正成为一种有前景的干预措施，用于管理DPN中的氧化应激和炎症。
方法 前瞻性、双盲、安慰剂对照研究，总共52名正在服用加巴喷丁或普瑞巴林的DPN受试者被随机分配为每日口服一次600毫克ALA或每日口服一次安慰剂，为期12周。在基线以及每次随访（第4、8和12周）时，使用振动觉阈值（VPT）、神经病变总症状评分6（NTSS-6）、通过12项简明健康调查（SF-12）问卷评估的生活质量（QOL）、氧化应激生物标志物（丙二醛（MDA）、一氧化氮（NO）和谷胱甘肽（GSH））以及炎症生物标志物（高敏C反应蛋白（hs-CRP））来评估治疗结果。在基线和第12周时检测神经元特异性烯醇化酶（NSE）水平。在筛查时和第12周时检测糖化血红蛋白（HbA1C）和安全参数。通过清点药丸评估对研究药物的依从性。记录报告的药物不良反应。
结果 总共52名受试者（男性 = 22名；女性 = 30名），平均年龄为55.63 ± 7.5岁，被随机分配接受ALA或安慰剂。与基线相比，在第12周时观察到ALA使VPT显著降低（从26.92 ± 3.58降至22.14 ± 1.94；p < 0.0001）。与安慰剂相比，ALA使NTSS-6、SF-12问卷评估的QOL、NSE水平、氧化生物标志物水平和炎症生物标志物等次要参数有显著改善。未报告严重不良事件。
结论 ALA通过其抗氧化和抗炎作用对DPN表现出保护作用，并且被发现具有良好的安全性。
