Validation of the Histamine- and Heat-Induced Axon-Reflex Flare Response in a Nonselected Population of People With Type 1 Diabetes.

Abstract

Introduction/aims: Diabetic peripheral neuropathy affects small nerve fibers early, but adequate evaluation has proven difficult. One method for functional assessment of small nerve fiber function is the axon-reflex flare (ARF) response. This study aimed to 1) validate the histamine-induced ARF response in a nonselected population with diabetes, 2) compare the response to that induced by local heating, and 3) compare both methods to an established method (quantitative sensory testing) in a nonselected population with diabetes.

Methods: Thirty-four participants with type 1 diabetes were included. The participants underwent a neurological examination, quantitative sensory testing, sural nerve conduction, and histamine- and heat-induced ARF response measurements by full-field laser speckle perfusion imaging after epidermal application of histamine and after local heating by 44^° Celsius thermode, respectively. Spearman's correlations were assessed. Logistic regression was used to generate receiver operating characteristic curves using the cold detection threshold of quantitative sensory testing as reference.

Results: The histamine-induced ARF had an area under the curve (AUC) of 0.82, a sensitivity of 67%, and a specificity of 70%. The heat-induced ARF had an AUC of 0.40, a sensitivity of 36%, and a specificity of 57%. No significant correlation between the histamine- and the heat-induced ARF responses was found.

Discussion: The histamine-induced ARF response is a valid marker for small fiber neuropathy even in nonselected populations with diabetes with good agreement with established markers and can thus be used for evaluation of C-fiber function. The lack of correlation with the heat-induced ARF may be due to insufficient heating.