Mechanisms of Venoarteriolar Reflex in Type 2 Diabetes with or without Peripheral Neuropathy

Abstract

The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.

Functional and structural markers of peripheral microvascular autonomic neuropathy

“…VSR was unable to differentiate between control subjects and patients with SFN. Previous studies showed VSR to successfully distinguish between groups of patients with peripheral neuropathy 12,13 . VSR is significantly influenced by a multitude of external factors, 35,36 but was found to be reproducible in standardized settings 37–39 …”

“…Previous studies showed VSR to successfully distinguish between groups of patients with peripheral neuropathy. 12,13 VSR is significantly influenced by a multitude of external factors, 35,36 but was found to be reproducible in standardized settings. [37][38][39] A high skin temperature is associated with the highest degree of reproducibility.…”

“…Although the peripheral resting microvascular blood flow is regulated by a combination of neurogenic and non‐neurogenic factors, rapid vasoconstriction responses are mediated through sympathetic nerve fibers 10,11 . LDF has previously been used successfully to identify subjects with dysautonomia and neuropathy 12,13 …”

“…10,11 LDF has previously been used successfully to identify subjects with dysautonomia and neuropathy. 12,13 Quantifying cutaneous microvascular blood vessel density and innervation (neurovascular contacts) has recently been described and proved successful in assessing peripheral autonomic nerve fiber damage. 14 The aim of the present study was to examine the applicability of these microvascular functional (LDF-assessed microvascular vasoconstriction reflexes) and structural (density of microvascular vessels and neurovascular contacts) markers as diagnostic tools in the evaluation of SFN.…”

Oral Glucose Load and Human Cutaneous Microcirculation: An Insight into Flowmotion Assessed by Wavelet Transform

“…Therefore, an appropriate knowledge of the mechanisms governing the microvascular function and dysfunction may help to prevent the progression or even the installation of certain diseases with an important vascular impact. Microvascular dysfunction is among the most important consequences of long-term hyperglycemia, one of the main features of diabetes mellitus, being characterized by impaired endothelium-dependent vasodi-lation [20], impaired vasomotion [21,22] and neurogenic regulation [23], together with increased capillary permeability [20].…”