Short-term metabolic change is associated with improvement in measures of diabetic neuropathy: a 1-year placebo cohort analysis.
OBJECTIVE
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.
Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, 200 Elizabeth Street, Toronto, Ontario, Canada. bruce.perkins@uhn.on.ca
B A
BA
Perkins
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Dholasania
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RA
Buchanan
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Bril
D000293:Adolescent; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult
D006442:Glycated Hemoglobin; D010919:Placebos; D014280:Triglycerides; C517652:hemoglobin A1c protein, human