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

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 ϭ 15) and epalrestat (150 mg/day) group (n ϭ 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 ϭ 0.044), constriction ratio (P ϭ 0.014), and maximum velocity of constriction (P ϭ 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 ϭ 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P ϭ 0.002 and P ϭ 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. Diabetes Care 24:1093-1098, 2001D iabetic neuropathy is generally classified into somatic and autonomic neuropathy. Although somatic neuropathy can be characterized by symptoms such as numbness, paresthesia, and abnormal sensation, the symptoms of autonomic neuropathy do not appear until the advanced stage.Diabetic autonomic neuropathy causes functional disorders of many organs, such as cardiovascular, gastrointestinal, genitourinary, metabolic, and pupillary dysfunctions. Among these, cardiovascular autonomic neuropathy may increase the risk of sudden death and affects the mortality of diabetic patients (1,2). Therefore, the diagnosis and treatment of autonomic neuropathy at an early stage is important for the management of diabetic patients.It is well known that diabetic autonomic neuropathy develops within a short duration of diabetes even when somatic neuropathy is not apparent (3,4). Furthermore, the abnormalities in pupillary functions can be detected earlier than those in cardiovascular autonomic functions and are considered the earliest signs of diabetic autonomic neuropathy (5-10). Therefore, the pupillary light reflex test has been used for evaluating diabetic autonomic neuropathy.It has been demonstrated that strict glycemic control can decrease the incidence of diabetic complications, including autonomic neuropathy (11). However, it is impossible to completely prevent the development of diabetic complications by glycemic control alone, except by performing a pancreas transplantation. Therefore, different t...

Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy

“…In our study, epalrestat was associated with a significantly shorter MFWL of the median motor nerve compared with the control group, which is in agreement with another study with mild neuropathy (17). Other ARIs, including fidarestat, ranirestat, and zenarestat, have also been reported to improve MNCV and MFWL.…”

“…MFWL may also be a useful index to evaluate diabetic neuropathy (17,18). In our study, epalrestat was associated with a significantly shorter MFWL of the median motor nerve compared with the control group, which is in agreement with another study with mild neuropathy (17).…”

“…Although several published reports have described the efficacy and safety of epalrestat (13)(14)(15)(16)(17), including a doubleblind, placebo-controlled study (13), no long-term or large population studies have been conducted. Therefore, the Aldose Reductase Inhibitor-Diabetes Complications Trial (ADCT) was initiated to evaluate the efficacy and safety of longterm administration of epalrestat in subjects with mild diabetic neuropathy.…”

Erythrocyte sorbitol level as a predictor of the efficacy of epalrestat treatment for diabetic peripheral polyneuropathy

“…To the best of our knowledge, this is the first study to demonstrate a correlation between erythrocyte sorbitol levels and changes in nerve function tests during ARI administration. Nakayama et al (2001) have reported that 24 weeks of epalrestat treatment ameliorated papillary light reflex and F-wave latency, but not nerve conduction velocity, in patients with mild diabetic neuropathy. On the other hand, ARI, zenarestat, has shown to reduce both erythrocyte and nerve sorbitol contents in a dose-dependent manner and that this sorbitol suppression was accompanied by significant improvements in the slowing down of nerve conduction velocity and the loss of small myelinated nerve fibers in patients with diabetic polyneuropathy (Greene, Arezzo, & Brown, 1999).…”

Emerging Therapies for Diabetic Neuropathy: A Clinical Overview

“…Improvement in nerve function and in upper limb symptoms suggest the potential for clinically significant drug effect, which is currently being studied in Phase III trials [25].…”