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.
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.
Kawai
Toshihide
T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. tkawai@sc.itc.keio.ac.jp
Takei
Izumi
I
Tokui
Mikiya
M
Funae
Osamu
O
Miyamoto
Kazunori
K
Tabata
Mitsuhisa
M
Hirata
Takumi
T
Saruta
Takao
T
Shimada
Akira
A
Itoh
Hiroshi
H
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003929:Diabetic Neuropathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013497:Sural Nerve / Q000503:physiopathology; D053778:Thiazolidines / Q000627:therapeutic use*; D013979:Tibial Nerve / Q000503:physiopathology
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D053778:Thiazolidines; C038131:epalrestat; C048496:N(6)-carboxymethyllysine; D012236:Rhodanine; D000449:Aldehyde Reductase; D008239:Lysine