title: 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.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. tkawai@sc.itc.keio.ac.jp
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kawai
authors.forename: Izumi
authors.initials: I
authors.lastname: Takei
authors.forename: Mikiya
authors.initials: M
authors.lastname: Tokui
authors.forename: Osamu
authors.initials: O
authors.lastname: Funae
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Mitsuhisa
authors.initials: M
authors.lastname: Tabata
authors.forename: Takumi
authors.initials: T
authors.lastname: Hirata
authors.forename: Takao
authors.initials: T
authors.lastname: Saruta
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D053778:Thiazolidines; C038131:epalrestat; C048496:N(6)-carboxymethyllysine; D012236:Rhodanine; D000449:Aldehyde Reductase; D008239:Lysine