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

Abstract

Background Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. Aims 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 and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h 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 were assessed by blood sample collection. Results 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. 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 Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

A correlation study of arterial stiffness, cardiac autonomic neuropathy and lipid profile in type 2 diabetes mellitus patients

“…It may be possible that dyslipidaemia may negatively affect the myelination status of the nerves, and thereby, it may cause dysregulation of ANS. [17,18] AIP index was also positively associated with CSBP and baPWV, which are non-invasive surrogate markers of arterial stiffness. Understandably, enhanced atherogenicity of plasma may escalate arterial stiffness.…”

Omentin1 ameliorates myocardial ischemia-induced heart failure via SIRT3/FOXO3a-dependent mitochondrial dynamical homeostasis and mitophagy

“…Furthermore, omentin could ameliorate doxorubicin-induced H9c2 cell apoptosis [ 9 ]. Similarly, most cross-sectional studies reported that the circulating omentin1 levels were lower in patients with ischemic stroke, metabolic syndrome, or type 2 diabetes compared with subjects without cardiovascular diseases [ 10 – 12 ]. All of these are consistent with observations from several studies that omentin1 levels were inversely associated with multiple cardiovascular risk factors including BMI, age, waist circumference, insulin resistance, glucose levels, and lipid levels [ 13 , 14 ].…”

Reactive Hyperemia and Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Patients: A Systematic Review of Randomized and Nonrandomized Clinical Trials

“…Of the articles reviewed herein, five showed differences in RH between healthy subjects and diabetic patients with and/or without neuropathy [15,30,33,57,58], while one study did not show such differences between healthy subjects and diabetic patients, but patients with diabetic ulcers had lower RH index values compared to healthy controls [59]. Another study found no significant difference in blood flow after a muscle strain that induced reactive hyperemia (PSRH) between normal subjects and diabetic non-smokers [43].…”

“…Nine studies (Table 2) compared reactive hyperemia between diabetic patients with and without CAN [15,20,30,43,[58][59][60][61][62]. Four of them measured reactive hyperemia using PAT [15,59,61,62], and only two found a significantly lower endothelial-function-derived measure of PAT in diabetic patients with CAN than in those without CAN [15,59]. Four studies measured reactive hyperemia using FMD.…”

“…Diabetic patients who had higher systolic blood pressure and heart rate and lower MSNA had lower endothelial function, as measured using PAT [15]. Diabetic patients with diabetic foot syndrome showed increased parasympathetic activity, decreased sympathetic activity, and decreased RH [59]. Smoking diabetic patients had a higher heart rate, less neurogenic activity, and less blood flow than non-smoking diabetics and healthy subjects [43].…”