Aldose Reductase Inhibition Ameliorates Pupillary Light Reflex and F-Wave Latency in Patients With Mild Diabetic Neuropathy

Aldose Reductase Inhibition Ameliorates Pupillary Light Reflex and F-Wave Latency in Patients With Mild Diabetic Neuropathy Mikihiro Nakayama , MD , Jiro Nakamura , MD , Yoji Hamada , MD , Sadao Chaya , MD , Ryuichi Mizubayashi , MD , Yutaka Yasuda , MD , Hideki Kamiya , MD , Naoki Koh , MD and Nigishi Hotta , MD Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan Abstract OBJECTIVE —The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. RESEARCH DESIGN AND METHODS —A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group ( n = 15) and epalrestat (150 mg/day) group ( n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed. RESULTS —The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli ( P = 0.044), constriction ratio ( P = 0.014), and maximum velocity of constriction ( P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat ( P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat ( P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity. CONCLUSIONS —These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy. AC, the maximum acceleration of constriction (mm/s2) ANOVA, analysis of variance ARI, aldose reductase inhibitor CR, constriction ratio [CR = (D1 – D2)/D1] D1, initial diameter before light stimulus (mm) D2, minimum diameter after light stimulus (mm) E/I ratio, ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval NCV, nerve conduction velocity QTc, corrected QT time T1, latency to constriction (ms) T2, time to half of the maximum constriction (ms) T3, time to the maximum constriction (ms) T5, recovery time (time