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

Abstract

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 N(ɛ)-carboxymethyl lysine (CML) as a parameter of advanced glycation end products (AGEs), lipid peroxide, and soluble vascular cell adhesion molecule (sVCAM)-1 as a parameter of angiopathy were measured before administration and after 1 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 1 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.

• Authors: Toshihide Kawai, Izumi Takei, Mikiya Tokui, Osamu Funae, Kazunori Miyamoto, Mitsuhisa Tabata, Takumi Hirata, Takao Saruta, Akira Shimada, Hiroshi Itoh
• Journal: Journal of diabetes and its complications (J Diabetes Complications) 2010 Nov-Dec Vol. 24 Issue 6 Pg. 424-32 ISSN: 1873-460X [Electronic] United States
• PMID: 19716319 (Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• Glycation End Products, Advanced
• Thiazolidines
• epalrestat
• N(6)-carboxymethyllysine
• Rhodanine
• Aldehyde Reductase
• Lysine

Topics

• Aldehyde Reductase (antagonists & inhibitors)
• Diabetes Mellitus, Type 2 (blood, complications)
• Diabetic Neuropathies (blood, drug therapy, physiopathology)
• Enzyme Inhibitors (therapeutic use)
• Female
• Glycation End Products, Advanced (blood)
• Humans
• Lysine (analogs & derivatives, blood)
• Male
• Middle Aged
• Neural Conduction (drug effects)
• Peripheral Nervous System Diseases (drug therapy, physiopathology)
• Rhodanine (analogs & derivatives, therapeutic use)
• Sural Nerve (physiopathology)
• Thiazolidines (therapeutic use)
• Tibial Nerve (physiopathology)