Elevated levels of interleukin-12/23p40 may serve as a potential indicator of dysfunctional heart rate variability in type 2 diabetes

• Published in: Cardiovascular diabetology Vol. 21; no. 1; p. 5
• Main Authors: Wegeberg, A M, Okdahl, T, Riahi, S, Ejskjaer, N, Pociot, F, Størling, J, Brock, B, Brock, C
• Format: Journal Article
• Language: English
• Published: England BioMed Central 06-01-2022; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer's disease; Antihypertensives; Autonomic nervous system; Biomarkers - blood; Blood pressure; Body mass index; Cardiovascular diseases; Cell adhesion; Chemokines; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes mellitus, type 2; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - diagnosis; Diabetic Cardiomyopathies - blood; Diabetic Cardiomyopathies - diagnosis; Diabetic Cardiomyopathies - etiology; Diabetic Cardiomyopathies - physiopathology; Diabetic neuropathy; Electrocardiography; Female; Heart diseases; Heart Rate; Hemoglobin; Humans; Hypertension; Inflammation; Inflammation Mediators - blood; Insulin; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - blood; Interleukin 12; Interleukin-12 Subunit p40 - blood; Kinases; Male; Middle Aged; Morbidity; Nervous system; Original Investigation; Predictive Value of Tests; Prognosis; Proteins; Regulation; Risk factors; Serum levels; Standard deviation; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; Up-Regulation; Vagus nerve; Vascular endothelial growth factor; Vascular Endothelial Growth Factor C - blood; Denmark; United States > US; Illinois; Diabetes mellitus, type 2; Cardiovascular diseases; Inflammation
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-021-01437-w

Systemic inflammatory processes plausibly contribute to the development of cardiovascular complications, causing increased morbidity and mortality in type 2 diabetes. Circulating inflammatory markers, i.e., interleukin (IL)-6 and tumour necrosis factor-α, are associated with neurocardiac measures. We examined a broad panel of various inflammatory and inflammation-related serum markers to obtain more detailed insight into the possible neuro-immune interaction between cardiovascular regulation and systemic level of inflammation.
Serum samples from 100 participants with type 2 diabetes were analysed. Heart rate variability, cardiovascular autonomic reflex tests, and cardiac vagal tone tests were performed based on electrocardiographic readings. Data regarding covariates (demographic-, diabetes-, and cardiovascular risk factors) were registered.
Increased serum levels of IL-12/IL-23p40 (p  < 0.01) and intercellular adhesion molecule (ICAM)-1 (p  < 0.007) were associated with diminished heart rate variability measures. After all adjustments, the associations between IL-12/23p40, SDANN and VLF persisted (p  = 0.001). Additionally, serum levels of vascular endothelial growth factor (VEGF)-C were associated with response to standing (p  = 0.005).
The few but robust associations between neurocardiac regulation and serum markers found in this study suggest systemic changes in proinflammatory, endothelial, and lymphatic function, which collectively impacts the systemic cardiovascular function. Our results warrant further exploration of IL-12/IL-23p40, ICAM-1, and VEGF-C as possible cardiovascular biomarkers in T2D that may support future decisions regarding treatment strategies for improved patient care.