Short-term metabolic change is associated with improvement in measures of diabetic neuropathy: a 1-year placebo cohort analysis

Diabet Med. 2010 Nov;27(11):1271-9. doi: 10.1111/j.1464-5491.2010.03110.x.


Aims: Randomized clinical trials have frequently shown improvement in diabetic sensorimotor polyneuropathy in placebo-treated participants, counter to the prevailing concept that it deteriorates with time. We aimed to determine the variables associated with this paradoxical nerve function improvement.

Methods: Participants with diabetic sensorimotor polyneuropathy randomized to placebo in a multi-centre, double-blind study were evaluated for the primary outcome of 1-year change in the summed sensory nerve conduction velocity of the bilateral sural and non-dominant median nerves. Association with clinical and biochemical variables measured at 13 time points were examined.

Results: The 134 participants had mild to moderate diabetic sensorimotor polyneuropathy of 4.6 years' duration and mean 1-year improvement of 2.0 ± 8.0 m/s. Primary outcome measures were available for 122 participants (91%). In multivariate analyses, the change in HbA(1c) and serum triglycerides from baseline to 2 months demonstrated the strongest association, even independent of baseline and end-of-study levels. According to quintiles of change, we determined thresholds: participants with salutary improvement in HbA(1c) (exceeding a drop of -0.8%) or whose triglycerides did not increase (by 0.32 mmol/l or more) experienced significant improvement (2.9 m/s), while those with salutary levels of both these variables had an exaggerated improvement (5.1 m/s). In comparison, those with non-salutary changes in both variables experienced a loss of -4.9 m/s (ANOVA P=0.0014).

Conclusions: In mild to moderate diabetic sensorimotor polyneuropathy, short-term improvements in glycaemic control and serum triglyceride levels have an independent, additive and durable effect on restoration of nerve function.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Neuropathies / drug therapy
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / physiopathology*
  • Female
  • Glycated Hemoglobin / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Neural Conduction / drug effects
  • Neural Conduction / physiology*
  • Placebos
  • Randomized Controlled Trials as Topic
  • Triglycerides / blood*
  • Young Adult


  • Glycated Hemoglobin A
  • Placebos
  • Triglycerides
  • hemoglobin A1c protein, human