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.
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MR and DZ contributed equally.
Collaborators The German Diabetes Study (GDS) Group consists of M. Roden (speaker), A.E. Buyken, J. Eckel, G. Geerling, H. Al-Hasani, C. Herder, A. Icks, J. Kotzka, O. Kuss, E. Lammert, J. Lundbom, K. Müssig, P. Nowotny, W. Rathmann, J. Szendroedi, D. Ziegler and their coworkers who are responsible for the design and performance of the GDS.
Contributors CH designed the study, researched data, contributed to data analysis, interpreted the data and wrote the manuscript. IS designed the study, performed the statistical analysis, interpreted the data, contributed to discussion and critically reviewed the manuscript. BN researched data and critically reviewed the manuscript. MC-K researched data, contributed to discussion and critically reviewed the manuscript. KS contributed to data analysis, contributed to discussion and critically reviewed the manuscript. PN, AS and SP researched data and critically reviewed the manuscript. JMK contributed to the statistical analysis, interpreted the data, contributed to discussion and critically reviewed the manuscript. KM and JS researched data, contributed to discussion and critically reviewed the manuscript. MR designed the study, contributed to discussion, critically reviewed and edited the manuscript. DZ designed the study, researched data, interpreted the data, contributed to discussion, critically reviewed and edited the manuscript. All authors approved of the final version of the manuscript.
Funding The German Diabetes Study was initiated and is performed by the DDZ, which is funded by the German Federal Ministry of Health (BMG) and the Ministry of Innovation, Science, Research and Technology (MIWF) of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research (BMBF) to the German Center for Diabetes Research (DZD e.V.) and by a grant of the Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases.
Competing interests None declared.
Ethics approval Ethics committee of Heinrich Heine University, Düsseldorf, Germany.
Provenance and peer review Not commissioned; externally peer reviewed.