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

Author: Anne-Marie L Wegeberg1,2, Tina Okdahl1, Tina Fløyel3, Christina Brock1,2, Niels Ejskjaer2,4,5, Sam Riahi6, Flemming Pociot3,7, Joachim Størling3,8, Birgitte Brock3
Author Information:
1 Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark.
2 Clinical Institute, Aalborg University, Aalborg, Denmark.
3 Steno Diabetes Center Copenhagen, Gentofte, Denmark.
4 Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark.
5 Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
6 Department of Cardiology, Aalborg University Hospital, Denmark.
7 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
8 Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Conference/Journal: Mediators Inflamm
Date published: 2020 Aug 18
Other: Volume ID: 2020 , Pages: 3590389 , Special Notes: doi: 10.1155/2020/3590389. , Word Count: 270

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-) 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.

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). 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.

PMID: 32908447 PMCID: PMC7450314 DOI: 10.1155/2020/3590389