Diabetic neuropathy and axon reflex-mediated neurogenic vasodilatation in type 1 diabetes

PLoS One. 2012;7(4):e34807. doi: 10.1371/journal.pone.0034807. Epub 2012 Apr 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Axons
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Diabetic Neuropathies / diagnostic imaging
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / physiopathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polyneuropathies / diagnostic imaging
  • Polyneuropathies / etiology
  • Polyneuropathies / physiopathology
  • ROC Curve
  • Reflex
  • Ultrasonography
  • Vasodilation*
  • Young Adult