Key result
Lower endothelial function is strongly linked to higher neuropathy disability scores.
Why the study?
Cardiovascular risk factors are established predictors of diabetic peripheral neuropathy, but the role of endothelial dysfunction as a linking mechanism was unclear.
Is endothelial dysfunction, as measured by flow-mediated dilation, associated with the severity of diabetic peripheral neuropathy?
Cross-Sectional (n=492)
No
Is endothelial dysfunction, as measured by flow-mediated dilation, associated with the severity of diabetic peripheral neuropathy?
Effect estimate: β = -0.24
p-value: p=< .001
Endothelial dysfunction occurs early in diabetes and is significantly associated with diabetic peripheral neuropathy, suggesting it acts as a mechanistic link between cardiovascular risk factors and microvascular complications.
Should not yet change DPN management; leaves open whether improving endothelial function alters neuropathy progression.
CONTEXT: Cardiovascular risk factors are well-known predictors of the development of diabetic peripheral neuropathy (DPN), which has traditionally been considered as a manifestation of diabetes-associated microangiopathy. Because endothelial dysfunction is strongly associated with all cardiovascular risk factors, we hypothesized that it may be a link between cardiovascular risk factors and DPN. OBJECTIVE: The primary objective of this study was to test whether endothelial dysfunction is a predictor of DPN. DESIGN AND SETTING: This is a cross-sectional analysis of a cohort composed of patients followed at the Microcirculatory Laboratory, Beth Israel Deaconess Medical Center. PATIENTS: Participants with diabetes without DPN (n = 192) and with DPN (n = 166), subjects with prediabetes (n = 75), and nondiabetic controls (n = 59) were included. INTERVENTIONS: Endothelial function was assessed with flow-mediated dilation (FMD) of the brachial artery. Inflammatory cytokines and biomarkers of endothelial function (soluble intercellular and vascular cell adhesion molecules) were quantified using a multiplex bead-based immunoassay. Neurological assessment included the neuropathy disability score (NDS). MAIN OUTCOME MEASURE: The relationship between FMD and NDS assessed using multiple linear regression. RESULTS: In addition to already known risk factors of DPN, FMD was strongly associated with NDS (β = -0.24; P < .001). Sensitivity analysis that removed FMD from the model provided similar results for soluble intercellular cell adhesion molecule-1, another biomarker of endothelial function. Confirmatory factor analysis further showed that endothelial dysfunction is a significant mediator between glycosylated hemoglobin and diabetes duration and diabetic complications. CONCLUSIONS: This study shows that endothelial dysfunction occurs early in the pathophysiology of diabetes and is a link between cardiovascular risk factors and DPN.
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Roustit et al. (2016) conducted a cross-sectional in Diabetic peripheral neuropathy (n=492). Endothelial dysfunction (assessed by flow-mediated dilation) was evaluated on Neuropathy disability score (NDS) (β = -0.24, p=< .001). Endothelial function, assessed by flow-mediated dilation, was strongly associated with the neuropathy disability score (β = -0.24; P < .001), linking cardiovascular risk factors and DPN.
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