title: Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial.
abstract: OBJECTIVE
  We aimed to analyze the impact of baseline factors on the efficacy of α-lipoic acid (ALA) over 4 years in the NATHAN 1 trial.
  
  
  METHODS
  This was a post-hoc analysis of the NATHAN 1 trial, a 4-year randomized study including 460 diabetic patients with mild-to-moderate polyneuropathy using ALA 600 mg qd or placebo. Amongst others, efficacy measures were the Neuropathy Impairment Score of the lower limbs (NIS-LL) and heart rate during deep breathing (HRDB).
  
  
  RESULTS
  Improvement and prevention of progression of NIS-LL (ΔNIS-LL≥2 points) with ALA vs. placebo after 4 years was predicted by higher age, lower BMI, male sex, normal blood pressure, history of cardiovascular disease (CVD), insulin treatment, longer duration of diabetes and neuropathy, and higher neuropathy stage. Participants treated with ALA who received ACE inhibitors showed a better outcome in HRDB after 4 years.
  
  
  CONCLUSIONS
  Better outcome in neuropathic impairments following 4-year treatment with α-lipoic acid was predicted by normal BMI and blood pressure and higher burden due to CVD, diabetes, and neuropathy, while improvement in cardiac autonomic function was predicted by ACE inhibitor treatment. Thus, optimal control of CVD risk factors could contribute to improved efficacy of α-lipoic acid in patients with higher disease burden.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany; Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany. Electronic address: dan.ziegler@ddz.uni-duesseldorf.de.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Freeman
authors.affiliation: MEDA Pharma GmbH & Co. KG, Bad Homburg, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Tritschler
authors.affiliation: Department of Medicine, EVMS Strelitz Diabetes Research Center and Neuroendocrine Unit, Eastern Virginia Medical School, Norfolk, VA, USA.
authors.forename: Aaron I
authors.initials: AI
authors.lastname: Vinik
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012074:Remission Induction; D008063:Thioctic Acid / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid
keywords: Autonomic function; Cardiovascular risk factors; Diabetic polyneuropathy; Neuropathic impairments; α-lipoic acid