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

Abstract

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.

Serum ICAM-1 as a Predictor of Prognosis in Patients with Acute Ischemic Stroke

“…ICAM-1 can produce soluble ICAM-1 through alternative splicing, which can be measured in various body fluids [9]. Studies have shown that ICAM-1 levels are elevated in atherosclerosis, cardiovascular disease, and metabolic vascular neuropathy [10][11][12][13]. However, there are still few studies on the correlation between ICAM-1 and AIS.…”