title: Inflammatory markers are associated with cardiac autonomic dysfunction in recent-onset type 2 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Biomarkers of inflammation were differentially associated with diminished cardiac autonomic dysfunction in recent-onset type 2 diabetes.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Schamarek
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen-Kirberg
authors.affiliation: German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Straßburger
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Kannenberg
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Püttgen
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Müssig
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Szendroedi
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Dan
authors.initials: D
authors.lastname: Ziegler
mesh_terms: D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D015716:Electrocardiography, Ambulatory / Q000379:methods; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators