Affiliation:
1. Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada
2. Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Canada
Abstract
OBJECTIVE
The prevailing hypothesis that early subclinical small-fiber injury precedes large-fiber damage in diabetic sensorimotor polyneuropathy (DSP) is based on lower intraepithelial nerve fiber density in type 2 prediabetic patients despite normal nerve conduction studies (NCSs). We aimed to confirm the same hypothesis in type 1 diabetic patients by examining whether: 1) subjects without DSP include a spectrum with both normal and abnormal small-fiber measures and 2) subjects with DSP have concurrent evidence of abnormal small-fiber measures.
RESEARCH DESIGN AND METHODS
A healthy control population (n = 53) was used to generate threshold values for four small-fiber tests: cooling detection thresholds (CDTs), laser Doppler imaging of heat-evoked flare (LDIflare), heart rate variability (HRV), and corneal confocal microscopy. Based on NCS results, type 1 diabetic patients (n = 131) were dichotomized according to the presence or absence of DSP.
RESULTS
Threshold values derived from healthy control subjects were 26.5°C, 1.4 cm2, 13%, and 12.9 mm/mm2 for CDT, LDIflare, HRV, and corneal nerve fiber length, respectively. Among type 1 diabetic patients, 57 of 131 had evidence of DSP, and 74 of 133 did not. Using abnormality of any small-fiber test to define small-fiber dysfunction, 55 of 57 (96.5%) DSP patients and 39 of 74 (52.7%) control subjects without DSP had concurrent small-fiber damage. The severity of small-fiber abnormalities worsened with an increasing number of NCS abnormalities (ANOVA, P < 0.01).
CONCLUSIONS
Our findings in type 1 diabetes support the prevailing hypothesis that small-fiber dysfunction occurs early in DSP. However, further research is required to determine which combination of small-fiber tests is most suitable as a surrogate marker in clinical trials.
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
102 articles.
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