Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes

Bhati, Pooja; Alam, Rizwan; Moiz, Jamal Ali; Hussain, M. Ejaz

doi:10.1007/s40200-019-00435-w

Cited by 22 publications

(22 citation statements)

References 55 publications

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“…The link between the in ammatory re ex and HRV is further substantiated in healthy individuals, as endotoxin-induced subclinical in ammation reduces HRV, while increased parasympathetic vagal activity decreases cytokine production (3,10). Similar ndings have been reported in type 2 diabetes, although these are highly associated with the presence of adipose in ammation (4,(11)(12)(13). Systemic low-grade in ammation has been linked to CAN in long-term type 1 diabetes (5,14), however, in both adolescent and recent onset diabetes, the in ammatory levels are not associated with HRV, suggesting that a neurodegenerative in ammation emerge years after diabetes onset (11,13).…”

Section: Introductionsupporting

confidence: 70%

Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes

Wegeberg

Okdahl

Fløyel

et al. 2020

Preprint

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Background A neuro-immune communication exists, and compiling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were 1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules and chemokines, and 2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone.Methods We included 104 adults with type 1 diabetes. Heart rate variability, time- and frequency domains, were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin (IL)-1α, IL-4, IL-12p70, IL-13, IL-17 and tumor necrosis factor (TNF)-α), adhesion molecules (E-selectin, P-selectin and intercellular adhesion molecule (ICAM)-1) and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4 and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration and smoking.Results Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2 and E-selectin, than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01).Conclusion Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuro-immune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.Trial registration: The study was approved by the North Denmark Regional Committee on Health Research Ethics (N2013-0077 and N2017-0045) and registered in public databases (Eudra CT 2013-004375-12 and clinicaltrials.gov NCT02138045.

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Section: Introductionsupporting

confidence: 70%

Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes

Wegeberg

Okdahl

Fløyel

et al. 2020

Preprint

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“…Direct neuronal Cardiovascular autonomic neuropathy is broadly described as a common and deadly complication of diabetes mellitus, but with pathophysiology remaining with lack of clarity (Fisher and Tahrani, 2017;Liu et al, 2020). Bhati et al (2019), in their recent study, confirmed the relationship between biomarkers of inflammation to the measures of cardiac vagal tone and HRV, linking the subclinical inflammation to CAN presentation. von Känel et al (2008), with his study team, described a significant association between systemic low-grade inflammatory activity and decrease in HRV in healthy subjects, confirming a positive relationship between plasma levels of interleukin (IL)-6 and soluble tissue factor (sTF), when HRV was low 4 .…”

Section: Discussionmentioning

confidence: 93%

Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

et al. 2021

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BackgroundWe are facing the outburst of coronavirus disease 2019 (COVID-19) defined as a serious, multisystem, disorder, including various neurological manifestations in its presentation. So far, autonomic dysfunction (AD) has not been reported in patients with COVID-19 infection.AimAssessment of AD in the early phase of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus).Patients and methodsWe analyzed 116 PCR positive COVID-19 patients. After the exclusion of 41 patients with associate diseases (CADG), partitioned to patients with diabetes mellitus, hypertension, and syncope, the remaining patients were included into a severe group (45 patients with confirmed interstitial pneumonia) and mild group (30 patients). Basic cardiovascular autonomic reflex tests (CART) were performed, followed by beat-to-beat heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) analysis, along with baroreceptor sensitivity (BRS). Non-linear analysis of HRV was provided by Poincare Plot. Results were compared to 77 sex and age-matched controls.ResultsAD (sympathetic, parasympathetic, or both) in our study has been revealed in 51.5% of severe, 78.0% of mild COVID-19 patients, and the difference compared to healthy controls was significant (p = 0.018). Orthostatic hypotension has been established in 33.0% COVID-19 patients compared to 2.6% controls (p = 0.001). Most of the spectral parameters of HRV and BPV confirmed AD, most prominent in the severe COVID-19 group. BRS was significantly lower in all patients (severe, mild, CADG), indicating significant sudden cardiac death risk.ConclusionCardiovascular autonomic neuropathy should be taken into account in COVID-19 patients’ assessment. It can be an explanation for a variety of registered manifestations, enabling a comprehensive diagnostic approach and further treatment.

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“…This study showed that the global association of CAN and coronary lesions might be independent of known factors in the pathogenesis of vascular endothelial injury and atherosclerosis in patients with type 2 diabetes mellitus. These findings suggest endothelial dysfunction and cardiac autonomic nervous dysfunction are related pathophysiologically in type 2 diabetes mellitus [ 27 ]. Additionally, we indicated that CAN may reflect the progression of coronary atherosclerosis in patients with type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Association between Cardiac Autonomic Neuropathy and Coronary Artery Lesions in Patients with Type 2 Diabetes

Liu

Yan

et al. 2020

Disease Markers

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Objective. Cardiac autonomic neuropathy (CAN) is a common and serious complication of diabetes mellitus with various systemic involvements, such as atherosclerotic cardiovascular disease. We aimed to evaluate the association between CAN and coronary artery lesions in patients with type 2 diabetes. Research Design and Methods. We retrospectively reviewed the medical records of 104 patients with type 2 diabetes and coronary artery disease (CAD). We evaluated heart rate variability (HRV) parameters (SDANN, SDNN, and pNN50) to assess cardiac autonomic function. The severity of coronary lesions was assessed by the Gensini scores and the number of affected vessels. Correlation analyses between HRV parameters and the severity of coronary lesions and clinical parameters were performed. Results. Spearman’s correlation analysis showed a significant negative correlation between SDANN and Gensini scores ( r = − 0.22 , P = 0.03 ). Interestingly, this finding remained significant after adjusting for clinical covariates ( r = − 0.23 , P = 0.03 ). However, there was no association between HRV parameters and the severity of coronary lesions as assessed by the number of affected vessels. Clinical parameters were not significantly correlated with HRV parameters (all P > 0.05 ). Conclusions. Cardiac autonomic neuropathy might be related to the degree of coronary atheromatous burden in patients with type 2 diabetes. Screening for cardiac autonomic neuropathy might potentially be beneficial in the risk stratification of patients with type 2 diabetes.

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Subclinical inflammation and endothelial dysfunction are linked to cardiac autonomic neuropathy in type 2 diabetes

Cited by 22 publications

References 55 publications

Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes

Circulating Inflammatory Markers are Inversely Associated with Heart Rate Variability Measures in type 1 Diabetes

Assessment of Autonomic Nervous System Dysfunction in the Early Phase of Infection With SARS-CoV-2 Virus

Association between Cardiac Autonomic Neuropathy and Coronary Artery Lesions in Patients with Type 2 Diabetes

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