title: Effect of rosuvastatin on diabetic polyneuropathy: a randomized, double-blind, placebo-controlled Phase IIa study.
abstract: BACKGROUND
  Diabetic neuropathy affects 50%-66% of patients with diabetes mellitus. Oxidative stress generates nerve dysfunction by causing segmental demyelinization and axonal degeneration. Antioxidants are considered to be the only etiologic management for diabetic polyneuropathy, and statins such as rosuvastatin increase nitric oxide bioavailability and reduce lipid peroxidation. The aim of this study was to evaluate the antioxidant effect of rosuvastatin in diabetic polyneuropathy.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled Phase IIa clinical trial in patients with type 2 diabetes and diabetic polyneuropathy (DPN) stage ≥1b. We allocated subjects to two parallel groups (1:1) that received rosuvastatin 20 mg or placebo for 12 weeks. Primary outcomes were neuropathic symptom score, disability score, and nerve conduction studies, and secondary outcomes were glycemic control, lipid and hepatic profile, lipid peroxidation, and nerve growth factor beta (NGF-β) levels.
  
  
  RESULTS
  Both groups were of similar age and duration since diagnosis of diabetes and DPN. We observed improvement of DPN in the rosuvastatin group from stage 2a (88.2%) to stage 1b (41.2%), improvement of neuropathic symptom score from 4.5±2 to 2.4±1.8, and significant (P=0.001) reductions of peroneal nerve conduction velocity (from 40.8±2.2 to 42.1±1.6 seconds) and lipid peroxidation (from 25.4±2 to 12.2±4.0 nmol/mL), with no significant change in glycemic control or β-NGF.
  
  
  CONCLUSIONS
  The severity, symptoms, and nerve conduction parameters of DPN improved after 12 weeks of treatment with rosuvastatin. These beneficial effects appear to be attributable to reductions in lipid peroxidation and oxidative stress.
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Jaime
authors.initials: J
authors.lastname: Hernández-Ojeda
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Román-Pintos
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Adolfo Daniel
authors.initials: AD
authors.lastname: Rodríguez-Carrízalez
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Troyo-Sanromán
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Ernesto Germán
authors.initials: EG
authors.lastname: Cardona-Muñoz
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: María Del Pilar
authors.initials: Mdel P
authors.lastname: Alatorre-Carranza
authors.affiliation: Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Jalisco, México.
authors.forename: Alejandra Guillermina
authors.initials: AG
authors.lastname: Miranda-Díaz
keywords: diabetic polyneuropathy; nerve conduction; nerve growth factor beta; oxidative stress; rosuvastatin