Diabetic Neuropathy and Axon Reflex-Mediated Neurogenic Vasodilatation in Type 1 Diabetes

OBJECTIVE Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical small fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging ("LDI(FLARE) area") in type 1 diabetes and in healthy volunteers. RESEARCH AND METHODS Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDI(FLARE) area (cm(2)) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers. We examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its severity. RESULTS Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDI(FLARE) area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDI(FLARE) area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDI(FLARE) area between all groups such that the ROC curve had an AUC of 0.72 and optimal sensitivity of 70% for the detection of clinical DSP. Use of a subclinical definition for DSP, according to subclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis higher HbA1c and body mass index had independent associations with smaller LDI(FLARE) area. CONCLUSIONS Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of early nerve dysfunction in DSP. Its independent association with glycemic exposure in diabetes subjects and both glycemic exposure and BMI in healthy volunteers highlights the existence of small-fibre dysfunction in the natural history of DSP.