Accelerated Intraepidermal Nerve Fiber Density (IENFD) Decline Precedes Progression to Neuropathic Symptoms in Patients with Diabetes
Abstract Number: 636-P
Authors: J. ROBINSON SINGLETON, CHARLES LATNER, COLLIN J. ARSENAULT, MICHAEL T. PORZIO, A. GORDON SMITH
Institutions: Salt Lake City, UT
Results: Once established, diabetic neuropathy has proven resistant to medical therapy. Presymptomatic detection would permit targeted early preventive treatment that might prove more effective. The Cutaneous Measures of Neuropathy in Diabetes (CMND) natural history cohort study compares peripheral nerve measures for their ability to predict progression to symptomatic diabetic neuropathy in a cohort of 210 type II diabetes subjects. Neuropathy designation requires symptoms or exam signs plus presence of two confirmatory abnormalities; NCS quantitative sensory testing, QSART or IENFD. Annually, a blinded Investigator interviews each CMND subject to determine if symmetrical, length dependent numbness or paresthesias are present. T-test statistics compare measures of peripheral nerve function and metabolic indices in the cohort progressing to neuropathy symptoms with indices for subjects without neuropathy, or with baseline neuropathy. Change in nerve measures over the first year was also compared between groups.
140 CMND subjects have been followed for three years. Of 84 subjects without baseline neuropathy, 17 (20%) developed neuropathy symptoms over the follow-up period. Mean baseline values for most nerve function tests were significantly worse for progressors than for the non-neuropathy cohort, and similar to those for the neuropathy cohort. In the first year mean IENFD at proximal and distal thigh and ankle decreased significantly, and cold detection threshold (CDT) percentile increased for progressors, but not for other cohorts. One year NCS, QSART, and vibration QST measures did not progress significantly for any group. Incident neuropathy subjects had significantly higher mean baseline triglycerides and lower HDL than both the non-neuropathy (p<0.005) and neuropathy cohorts (p<0.05). Baseline age, BMI and HgbA1c did not differ significantly between groups. IENFD and CDT are dynamic small fiber measures that may allow presymptomatic diabetic patients at high neuropathy risk to be recognized as targets for early preventive therapy.