Inflammatory markers are associated with cardiac autonomic dysfunction in recent-onset type 2 diabetes

Heart. 2017 Jan 1;103(1):63-70. doi: 10.1136/heartjnl-2015-309181. Epub 2016 Aug 1.


Objective: Cardiovascular autonomic neuropathy is a common but underestimated diabetes-related disorder. Associations between cardiovascular autonomic dysfunction and subclinical inflammation, both risk factors of diabetic comorbidities and mortality, have been proposed in non-diabetic populations, while data for type 1 and type 2 diabetes are conflicting. Our aim was to investigate associations between inflammation-related biomarkers and cardiac autonomic dysfunction in patients with diabetes.

Methods: We characterised the associations between seven biomarkers of subclinical inflammation and cardiac autonomic dysfunction based on heart rate variability and cardiovascular autonomic reflex tests (CARTs) in 161 individuals with type 1 and 352 individuals with type 2 diabetes (time since diagnosis of diabetes <1 year). Analyses were adjusted for age, sex, anthropometric, metabolic and lifestyle factors, medication and cardiovascular comorbidities.

Results: In individuals with type 2 diabetes, higher serum interleukin (IL)-18 was associated with lower vagal activity (p≤0.015 for association with CARTs), whereas higher levels of total and high-molecular-weight adiponectin showed associations with very low frequency power, an indicator of reduced sympathetic activity (p≤0.014). Higher levels of soluble intercellular adhesion molecule-1 were associated with indicators of both lower vagal (p=0.025) and sympathetic (p=0.008) tone, soluble E-selectin with one indicator of lower vagal activity (p=0.047). Serum C-reactive protein and IL-6 were also related to cardiac autonomic dysfunction, but these associations were explained by confounding factors. No consistent associations were found in individuals with type 1 diabetes.

Conclusions: Biomarkers of inflammation were differentially associated with diminished cardiac autonomic dysfunction in recent-onset type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autonomic Nervous System / physiopathology
  • Autonomic Nervous System Diseases / blood
  • Autonomic Nervous System Diseases / etiology*
  • Autonomic Nervous System Diseases / physiopathology
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / physiopathology
  • Electrocardiography, Ambulatory / methods
  • Female
  • Heart Rate / physiology
  • Humans
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / physiopathology
  • Inflammation Mediators / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Inflammation Mediators