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

Toshihide Kawai, Izumi Takei, Mikiya Tokui, Osamu Funae, Kazunori Miyamoto, Mitsuhisa Tabata, Takumi Hirata, Takao Saruta, Akira Shimada, Hiroshi Itoh

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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 ε-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.

Original languageEnglish
Pages (from-to)424-432
Number of pages9
JournalJournal of Diabetes and its Complications
Volume24
Issue number6
DOIs
Publication statusPublished - 2010 Nov

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Aldehyde Reductase
Diabetic Neuropathies
Neural Conduction
Peripheral Nervous System Diseases
Type 2 Diabetes Mellitus
Tibial Nerve
Sural Nerve
Advanced Glycosylation End Products
Vascular Cell Adhesion Molecule-1
Lipid Peroxides
Lower Extremity
Control Groups
epalrestat
N(6)-carboxymethyllysine
Serum

Keywords

  • Diabetic peripheral neuropathy
  • Epalrestat
  • N-Carboxymethyl lysine (CML)
  • Nerve conduction study

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

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. / Kawai, Toshihide; Takei, Izumi; Tokui, Mikiya; Funae, Osamu; Miyamoto, Kazunori; Tabata, Mitsuhisa; Hirata, Takumi; Saruta, Takao; Shimada, Akira; Itoh, Hiroshi.

In: Journal of Diabetes and its Complications, Vol. 24, No. 6, 11.2010, p. 424-432.

Research output: Contribution to journalArticle

Kawai, Toshihide ; Takei, Izumi ; Tokui, Mikiya ; Funae, Osamu ; Miyamoto, Kazunori ; Tabata, Mitsuhisa ; Hirata, Takumi ; Saruta, Takao ; Shimada, Akira ; Itoh, Hiroshi. / 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. In: Journal of Diabetes and its Complications. 2010 ; Vol. 24, No. 6. pp. 424-432.
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T1 - 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

AU - Kawai, Toshihide

AU - Takei, Izumi

AU - Tokui, Mikiya

AU - Funae, Osamu

AU - Miyamoto, Kazunori

AU - Tabata, Mitsuhisa

AU - Hirata, Takumi

AU - Saruta, Takao

AU - Shimada, Akira

AU - Itoh, Hiroshi

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AB - 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 ε-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.

KW - Diabetic peripheral neuropathy

KW - Epalrestat

KW - N-Carboxymethyl lysine (CML)

KW - Nerve conduction study

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