Article type
Year
Abstract
Introduction: Peripheral neuropathy is one of the most common and disabling longterm sequaelae of diabetes mellitus. Typical manifestations are represented by loss of sensation in the feet, development of ulcers, deformations, and finally, gangrene, often resulting in amputations. A likely mechanism for the pathogenesis of diabetic neuropathy appears to be the polyol pathway hypothesis characterized by an accumulation of sorbitol and fructose with the nerves. Inhibitors of aldose reductase (ARIs), the first end rate-limiting enzyme of the poliol pathway, may prevent these abnormalities in diabetic animals. With this rationale, ARIs have thus been proposed and are increasingly used in many countries for the prophylaxis and treatment of diabetic neuropathy.
Objective: The aim of this systematic overview was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular attention to type and clinical relevance of the end-point used and to the consistency in the results across studies.
Methods: Fifteen randomised clinical trials comparing ARIs with placebo, published between 1981 and 1992, were identified by searching MEDLINE for specific medical heading and by inspecting the bibliographies of original and review articles on the treatment of diabetic neuropathy. Nerve conduction velocity (NCV) was the only end-point reported in most trials. Treatment effect was thus evaluated in terms of NCV improvement in 4 different nerves: median motor (937 patients from 15 trials), median sensory (479 patients from 9 trials), peroneal motor (757 patients from 10 trials), and sural sensory (440 patients from 8 trials).
Results: Overall pooled analysis showed a moderate yet statistically significant improvement in median motor NCV in the treated group as compared with the control group (mean 0.82 m/sec; 95% CI 0.30 to 1.34 m/sec). For peroneal, median sensory, and sural nerves results did not show any benefit for patients treated with ARIs.
Discussion: A very 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.
Objective: The aim of this systematic overview was to review existing evidence on the effectiveness of ARIs in the treatment of peripheral diabetic neuropathy, with particular attention to type and clinical relevance of the end-point used and to the consistency in the results across studies.
Methods: Fifteen randomised clinical trials comparing ARIs with placebo, published between 1981 and 1992, were identified by searching MEDLINE for specific medical heading and by inspecting the bibliographies of original and review articles on the treatment of diabetic neuropathy. Nerve conduction velocity (NCV) was the only end-point reported in most trials. Treatment effect was thus evaluated in terms of NCV improvement in 4 different nerves: median motor (937 patients from 15 trials), median sensory (479 patients from 9 trials), peroneal motor (757 patients from 10 trials), and sural sensory (440 patients from 8 trials).
Results: Overall pooled analysis showed a moderate yet statistically significant improvement in median motor NCV in the treated group as compared with the control group (mean 0.82 m/sec; 95% CI 0.30 to 1.34 m/sec). For peroneal, median sensory, and sural nerves results did not show any benefit for patients treated with ARIs.
Discussion: A very 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.