大剂量α-硫辛酸治疗糖尿病周围神经病变的有效性和安全性评价

Efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropathy

目的 观察口服较大剂量α-硫辛酸对糖尿病神经病变的治疗作用与安全性.方法 采用随机、双盲、多中心与安慰剂对照方法,共从5个中心入选236例有临床症状的糖尿病神经病变患者,口服α-硫辛酸（117例）1800 mg/d或安慰剂（119例）12周,主要终点指标为总神经症状积分,次要终点指标包括神经传导速度、各神经症状积分、HbA1c和安全性指标,分别在随访前和治疗后2、4、8、12周观察这些指标的变化,统计分析两组间差别.结果 经过α-硫辛酸治疗12周后,73.3%患者神经症状显著改善,对照组为18.3% 总神经症状积分减少2.6±2.3,显著高于对照组的0.7±1.4（P＜0.05） 2周随访时,两组症状改变量差异有统计学意义（P＜0.05）.α-硫辛酸对疼痛、麻木、烧灼感和其他感觉异常均有较好的疗效,症状积分均较入组前显著减少（P＜0.05） 但是神经传导速度在治疗前后无改变.12周观察期间,α-硫辛酸组HbA1c进一步降低 但是副反应发生率较高（25.4%）,以咽喉部至胃部灼热感为主,未见严重不良反应.结论 在安全的基础上,口服较大剂量α-硫辛酸对改善糖尿病神经病变的症状疗效显著,在2周内就能使症状显著减轻.

Objective To evaluate the efficacy and safety of high-dose α-lipoic acid in the treatment of diabetic polyneuropthy with regards to sensory symptoms and nerve conduction velocity. Methods A total of 236 diabetics with symptomatic polyneuropathy were enrolled into this 5-center, randomized,double-blind and placebo-controlled study of α-lipoic acid 1800 mg daily （ n = 117） or matching placebo （ n = 119） for 12 weeks. The primary outcome was total symptom score （TSS）. Secondary end points included nerve conduction velocity, individual symptom score, HbA1c and safety parameters. The above parameters were reviewed and recorded at zero point and after treatment for 2, 4, 8, 12 weeks separately. Results 73. 27%patients with symptomatic polyneurnpathy improved after treatment with α-lipoic acid for 12 weeks versus 18.27% with placebo. TSS declined by 2.6 ±2. 3 with α-lipoic acid. And it was more than 0. 7 ± 1.4 versus placebo （P 〈 0. 05 ）. TSS decreased quickly after treatment with α-lipoic acid for 2 weeks （P 〈 0. 05 ）. And it was better than placebo. Individual symptom scores of pain, extremity numbness, burning sensation or resting abnormal sensations were significantly diminished as compared to those before treatment and placebo group （ all P 〈 0. 05 ）. Nerve conduction velocity had no change. HbA l c further decreased at the end of trial after α-lipoic acid treatment （ P 〈 0. 05 ）. The incidence rates of adverse effects were 25.4% vs 11.8% in the treatment and control groups. The major manifestation was burning sensation from throat to stomach （ 12. 7% ）. Conclusion Oral treatment with high-dose α-lipoic acid for 12 weeks may improve symptoms in patients with diabetic polyneuropathy. Dose of 600mg thrice daily for 2 weeks has marked effects with a reasonable safety.