Objective: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating may reflect early, pre-clinical\nsmall fibre dysfunction. We aimed to evaluate the distribution of the vascular flare area measured by laser doppler imaging\n(ââ?¬Ë?ââ?¬Ë?LDIFLARE areaââ?¬â?¢Ã¢â?¬â?¢) in type 1 diabetes and in healthy volunteers.\nResearch and Methods: Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor\npolyneuropathy (DSP), LDIFLARE area (cm2) was determined in 89 type 1 diabetes subjects matched to 64 healthy volunteers.\nWe examined the association and diagnostic performance of LDI with clinical and subclinical measures of DSP and its\nseverity.\nResults: Compared to the 64 healthy volunteers, the 56 diabetes controls without DSP had significantly lower LDIFLARE area\n(p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP\n(p = 0.002). There was considerable overlap in LDIFLARE area between all groups such that the ROC curve had an AUC of 0.72\nand optimal sensitivity of 70% for the detection of clinical DSP. Use of a subclinical definition for DSP, according to\nsubclinical sural nerve impairment, was associated with improved AUC of 0.75 and sensitivity of 79%. In multivariate analysis\nhigher HbA1c and body mass index had independent associations with smaller LDIFLARE area.\nConclusions: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of early\nnerve dysfunction in DSP. Its independent association with glycemic exposure in diabetes subjects and both glycemic\nexposure and BMI in healthy volunteers highlights the existence of small-fibre dysfunction in the natural history of DSP.
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