Predictors of improvement and progression of diabetic polyneuropathy following treatment with α-lipoic acid for 4 years in the NATHAN 1 trial

J Diabetes Complications. 2016 Mar;30(2):350-6. doi: 10.1016/j.jdiacomp.2015.10.018. Epub 2015 Nov 10.


Aims: 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.

Keywords: Autonomic function; Cardiovascular risk factors; Diabetic polyneuropathy; Neuropathic impairments; α-lipoic acid.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / therapeutic use*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Remission Induction
  • Thioctic Acid / therapeutic use*
  • Treatment Outcome


  • Antioxidants
  • Thioctic Acid