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), LDIFLARE 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 LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE 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 LDIFLARE area. Conclusions: Axon reflex-mediated neurogenic vasodilatation in response to cutaneous heating is a biomarker of earl

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 ( LDIFLARE area ) in type 1 diabetes and in healthy volunteers. Research and Methods: Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm2) 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 LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE 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 LDIFLARE 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. © 2012 Nabavi Nouri et al

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 ( LDIFLARE area ) in type 1 diabetes and in healthy volunteers. Research and Methods: Concurrent with clinical and electrophysiological examination to classify diabetic sensorimotor polyneuropathy (DSP), LDIFLARE area (cm2) 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 LDIFLARE area (p = 0.006). The 33 diabetes cases with DSP had substantially lower LDIFLARE area as compared to controls without DSP (p = 0.002). There was considerable overlap in LDIFLARE 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 LDIFLARE 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. © 2012 Nabavi Nouri et al

Box-And-Whisker Plots Demonstrating The Distribution Of LDI_FLARE Area In 64 Healthy Volunteers And 89 Type 1 Diabetes Subjects According To Neuropathy Status.

<p>Compared to the healthy volunteer group LDI_FLARE area was significantly smaller in subjects with type 1 diabetes without DSP (p = 0.006). Compared to subjects with type 1 diabetes controls without DSP, LDI_FLARE area was smaller in cases with DSP (p = 0.0.0002). As indicated in the figure, among controls the LDI_FLARE area was not different according to presence or absence of subclinical sural nerve impairment. Similarly, the LDI_FLARE area was similar among cases with DSP regardless of severity. The criteria for mild neuropathy were two or more abnormal nerve conduction parameters in the lower limb (sural and peroneal nerve distributions), and moderate and severe neuropathy were defined by four and five abnormal parameters, respectively. NCS, nerve conduction study. LDI_FLARE, laser doppler imaging flare. DSP, diabetic sensorimotor polyneuropathy.</p

Clinical characteristics of the 64 healthy volunteers and of the 89 type 1 diabetes participants according to diabetic sensorimotor polyneuropathy status.

<p>Plus-minus values are means ± SD. [IQR] represents the interquartile range.</p>*<p>P values for categorical variables were calculated with the χ2 test, and ANOVA was used for continuous variables.</p>†<p>TCNS, Toronto clinical Neuropathy score. Scores of 0–5 are generally considered to represent low likelihood of DSP, 6–8 represents likelihood of mild neuropathy, 9–12 represent likelihood of moderate neuropathy, while 12–19 represent severe neuropathy.</p>‡<p>Axon-reflex mediated neurogenic vasodilatation by the laser doppler imaging flare method.</p

Regression Analysis Of LDI_FLARE Area And Baseline Demographics.

*<p>The multivariate model included the variables that were significant in univariate analysis in either the healthy volunteer of type 1 diabetes cohorts. Direct measures of neuropathy – which included the TCNS and the nerve conduction studies – were not considered in the multivariate analysis.</p><p>HbA1c, glycated hemoglobin A1c.</p