Nicolucci A, Carinci F, Cavaliere D, Scorpiglione N, Belfiglio M, Labbrozzi D, Mari E, Benedetti M M, Tognoni G, Liberati A
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Milano, Italy.
Diabet Med. 1996 Dec;13(12):1017-26. doi: 10.1002/(SICI)1096-9136(199612)13:12<1017::AID-DIA252>3.0.CO;2-Z.
Peripheral neuropathy is one of the most common and disabling long-term sequelae of diabetes mellitus. Aldose reductase inhibitors (ARIs) have been proposed and are increasingly used in many countries for the prevention and treatment of diabetic neuropathy. The aim of this study was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular reference to the type and clinical relevance of the end point used and to the consistency of results across studies. Thirteen randomized clinical trials (RTCs) comparing ARIs with placebo, published between 1981 and 1993 were included in the meta-analysis. Nerve conduction velocity (NCV) was the only end point reported in all trials. Treatment effect was thus evaluated in terms of NCV mean difference in four different nerves: median motor, median sensory, peroneal motor, and sural sensory. A statistically significant reduction in decline of median motor NCV was present in the treated group as compared to the control group (mean 0.91 ms-1; 95% CI 0.41-1.42 ms-1). For peroneal motor, median sensory, and sural sensory nerves results did not show any clear benefit for patients treated with ARIs. When the analysis was limited to trials with at least 1-year treatment duration, a significant effect was present for peroneal motor NCV (mean 1.24 ms-1; 95% CI 0.32-2.15 ms-1) and a benefit of borderline statistical significance was also present for median motor NCV (mean 0.69 ms-1; 95% CI-0.07-1.45 ms-1). A heterogeneous picture emerged when looking at the results of different studies and serious inconsistencies were also present in the direction of treatment effects among nerves in the same studies. Although the results of 1-year treatment on motor NCV seem encouraging, the uncertainty about the reliability of the end-point employed and the short treatment duration do not allow any clear conclusion about the efficacy of ARIs in the treatment of peripheral diabetic neuropathy.
周围神经病变是糖尿病最常见且致残的长期后遗症之一。醛糖还原酶抑制剂（ARIs）已被提出并在许多国家越来越多地用于预防和治疗糖尿病神经病变。本研究的目的是回顾关于ARIs治疗糖尿病周围神经病变有效性的现有证据，特别提及所使用终点的类型和临床相关性以及各研究结果的一致性。纳入荟萃分析的是1981年至1993年间发表的13项比较ARIs与安慰剂的随机临床试验（RTCs）。神经传导速度（NCV）是所有试验中唯一报告的终点。因此，根据四条不同神经（正中运动神经、正中感觉神经、腓总运动神经和腓肠感觉神经）的NCV平均差异评估治疗效果。与对照组相比，治疗组正中运动神经NCV下降有统计学显著降低（平均0.91ms-1；95%CI 0.41 - 1.42ms-1）。对于腓总运动神经、正中感觉神经和腓肠感觉神经，结果未显示ARIs治疗的患者有任何明显益处。当分析限于治疗持续时间至少为1年的试验时，腓总运动神经NCV有显著效果（平均1.24ms-1；95%CI 0.32 - 2.15ms-1），正中运动神经NCV也有边缘统计学显著益处（平均0.69ms-1；95%CI - 0.07 - 1.45ms-1）。查看不同研究结果时出现了异质性情况，同一研究中不同神经的治疗效果方向也存在严重不一致。尽管1年治疗对运动神经NCV的结果似乎令人鼓舞，但所采用终点的可靠性不确定以及治疗持续时间短，无法就ARIs治疗糖尿病周围神经病变的疗效得出任何明确结论。
