ASSESSMENT OF HEART RATE VARIABILITY (HRV) IN SUBJECTS WITH TYPE 2 DIABETES MELLITUS WITH AND WITHOUT DIABETIC FOOT: CORRELATIONS WITH ENDOTHELIAL DYSFUNCTION INDICES AND MARKERS OF ADIPO-INFLAMMATORY DYSFUNCTION

The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices.

Methods: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-hour ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 [Ed1] were assessed by blood sample collection.

Results: Patients with diabetic ulcers showed lower mean diastolic blood pressure values ​​than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values ​​and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance.

Discussion: Endothelial dysfunction and reduced sympathetic activity are closely related to the pathogenesis of diabetic ulcers, as endothelial dysfunction and the consequent microangiopathy of the vasa nervorum involve a downregulation of the small autonomic-sympathetic fibers present in the periphery.