TY - JOUR

T1 - Circulating Inflammatory Markers Are Inversely Associated with Heart Rate Variability Measures in Type 1 Diabetes

AU - Wegeberg, Anne-Marie L.

AU - Okdahl, Tina

AU - Fløyel, Tina

AU - Brock, Christina

AU - Ejskjaer, Niels

AU - Riahi, Sam

AU - Pociot, Flemming

AU - Størling, Joachim

AU - Brock, Birgitte

PY - 2020

Y1 - 2020

N2 - Introduction. A neuroimmune communication exists, and compelling 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.Materials and Methods. We included 104 adults with type 1 diabetes. Heart rate variability, time domain, 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-) 1 alpha, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-)alpha), 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-1 alpha, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1 alpha, IL-4, IL-12, TNF-alpha, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01).Discussion. 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 neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.

AB - Introduction. A neuroimmune communication exists, and compelling 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.Materials and Methods. We included 104 adults with type 1 diabetes. Heart rate variability, time domain, 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-) 1 alpha, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-)alpha), 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-1 alpha, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1 alpha, IL-4, IL-12, TNF-alpha, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (p>0.01).Discussion. 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 neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.

KW - CARDIAC VAGAL TONE

KW - CARDIOVASCULAR-DISEASE

KW - COMPLICATIONS

KW - DYSFUNCTION

KW - NEUROPATHY

KW - MELLITUS

U2 - 10.1155/2020/3590389

DO - 10.1155/2020/3590389

M3 - Journal article

C2 - 32908447

VL - 2020

JO - Mediators of Inflammation

JF - Mediators of Inflammation

SN - 0962-9351

M1 - 3590389

ER -