Effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy in patients with type 2 diabetes, in relation to suppression of Nε-carboxymethyl lysine

Objective: We investigated the efficacy of epalrestat, an aldose reductase inhibitor, for diabetic peripheral neuropathy in Japanese patients with type 2 diabetes. Methods: A total of 38 type 2 diabetic patients (22 men and 16 women; mean +/- S.E.M. age 63.3 +/- 1.0 years; duration of diabetes 9.6 +/- 0.8 years) with diabetic neuropathy were newly administered 150 mg/day epalrestat (EP group). Motor nerve conduction velocity (MCV), sensory nerve conduction velocity (SCV), and minimum F-wave latency were evaluated before administration of epalrestat and after 1 and 2 years. Serum Ne-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-I as a parameter of angiopathy were measured before administration and after I year. We compared the results with those of 36 duration of diabetes-matched type 2 diabetic patients (mean +/- S.E.M. duration of diabetes 8.2 +/- 0.7 years) as control (C group). Results: The EP group showed significant suppression of deterioration of MCV (P<.01) and minimum F-wave latency (P<.01) in the tibial nerve and SCV (P<.05) in the sural nerve compared to those in the C group after 2 years. There was a significant difference in change in CML level between groups (-0.18 +/- 0.13 mU/ml in the EP group vs. +0.22 +/- 0.09 mU/ml in the C group, P<.05) after I year. Conclusions: Epalrestat suppressed the deterioration of diabetic peripheral neuropathy, especially in the lower extremity. Its effects might be mediated by improvement of the polyol pathway and suppression of production of AGEs. (C) 2010 Elsevier Inc. All rights reserved.