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

Cardiovasc Diabetol. 2022 Jan 6;21(1):5. doi: 10.1186/s12933-021-01437-w.

Abstract

Background: 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.

Methods: 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.

Results: 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).

Discussion: 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.

Keywords: Cardiovascular diseases; Diabetes mellitus, type 2; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • 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
  • Electrocardiography
  • Female
  • Heart Rate*
  • Humans
  • Inflammation Mediators / blood*
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-12 Subunit p40 / blood*
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Up-Regulation
  • Vascular Endothelial Growth Factor C / blood

Substances

  • Biomarkers
  • ICAM1 protein, human
  • IL12B protein, human
  • Inflammation Mediators
  • Interleukin-12 Subunit p40
  • VEGFC protein, human
  • Vascular Endothelial Growth Factor C
  • Intercellular Adhesion Molecule-1