Pfeifer M A, Schumer M P, Gelber D A
Department of Internal Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858, USA.
Diabetes. 1997 Sep;46 Suppl 2:S82-9. doi: 10.2337/diab.46.2.s82.
Despite numerous attempts over 16 years, the results of aldose reductase inhibitor (ARI) trials for the treatment of diabetic neuropathy have not proven efficacy. This paper reviews each of the ARI trials, examines confounding factors, and proposes a future course. The confounding factors considered are pharmacokinetics (ARI penetration of human nerve), length of trial (in terms of the natural history of diabetic neuropathy), trial endpoints (reversibility or slowing of progression), reproducibility of clinical measurements (in terms of power calculations), standardization and quality control of endpoints, and clinically meaningful differences in endpoints. We conclude that ARIs are most likely to have a beneficial effect in the management of diabetic distal symmetrical polyneuropathy and autonomic neuropathy but that the clinical role of ARIs is to slow the progression of diabetic neuropathy rather than to reverse it. Future trials should be designed with adequate statistical power, with consideration of the variability of the endpoint measurements for long enough duration, and with rigorous quality control to definitively confirm the utility of ARIs in the treatment of diabetic distal symmetrical polyneuropathy and autonomic neuropathy.
尽管在16年里进行了无数次尝试，但醛糖还原酶抑制剂（ARI）治疗糖尿病神经病变的试验结果尚未证实其有效性。本文回顾了每项ARI试验，研究了混杂因素，并提出了未来的研究方向。所考虑的混杂因素包括药代动力学（ARI在人体神经中的渗透情况）、试验时长（根据糖尿病神经病变的自然病程）、试验终点（可逆性或进展减缓）、临床测量的可重复性（根据功效计算）、终点的标准化和质量控制，以及终点在临床上的有意义差异。我们得出结论，ARI最有可能在糖尿病远端对称性多发性神经病变和自主神经病变的管理中产生有益效果，但ARI的临床作用是减缓糖尿病神经病变的进展，而非逆转病变。未来的试验设计应具备足够的统计功效，考虑终点测量的变异性并持续足够长的时间，同时进行严格的质量控制，以明确证实ARI在治疗糖尿病远端对称性多发性神经病变和自主神经病变中的效用。
