title: Osteopontin and osteoprotegerin levels in type 2 diabetes and their association with cardiovascular autonomic function.
abstract: OBJECTIVE
  Osteopontin (OPN) and osteoprotegerin (OPG) are bone metabolism biomarkers potentially associated with nerve function. We evaluated the association of cardiovascular autonomic nerve function, OPN, and OPG in 50 individuals with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  RR-variation during deep breathing (i.e., mean circular resultant (MCR) and expiration/inspiration (E/I) ratio) was used to assess parasympathetic nerve function. Participants' demographics, HbA1c, 25-hydroxyvitamin D (25(OH)D), BMI, HOMA-IR, calcium, parathyroid hormone, creatinine, OPN, and OPG were determined.
  
  
  RESULTS
  Using stepwise multiple linear regression analysis with MCR or E/I ratio as the dependent variable, OPN was independently associated with reduced autonomic function. A previous report showed a significant association of cardiovascular autonomic function with age, 25(OH)D insufficiency, and the interaction of age×25(OH)D insufficiency. Here we report a novel association for OPN and its interaction with age indicating that for those who are younger, elevated OPN levels are related to a greater loss of autonomic function (MCR model R2=0.598, p<0.001; E/I model R2=0.594, p<0.001).
  
  
  CONCLUSIONS
  Our results suggest that OPN is associated with reduced parasympathetic function, particularly in younger individuals with T2DM. Further studies are needed to determine if OPN is neuroprotective, involved in the pathogenesis of autonomic dysfunction, or a bystander.
authors.affiliation: Department of Medical Laboratory Sciences, University of Delaware, Newark, DE, USA; Diabetes and Metabolic Research Center, Christiana Care Health System, Newark, DE, USA. Electronic address: rmaser@udel.edu.
authors.forename: Raelene E
authors.initials: RE
authors.lastname: Maser
authors.affiliation: Diabetes and Metabolic Research Center, Christiana Care Health System, Newark, DE, USA; Diabetes and Metabolic Diseases Center, Christiana Care Health System, Wilmington, DE, USA.
authors.forename: M James
authors.initials: MJ
authors.lastname: Lenhard
authors.affiliation: Biostatistics Core Facility, University of Delaware, Newark, DE, USA.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Pohlig
authors.affiliation: Biomedical Research & Analysis Laboratory, Nemours Children's Specialty Care & Mayo Clinic College of Medicine, Jacksonville, FL, USA.
authors.forename: P Babu
authors.initials: PB
authors.lastname: Balagopal
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D002319:Cardiovascular System / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*; D053244:Osteoprotegerin / Q000097:blood*; D012119:Respiration; D055815:Young Adult
chemical_list: D015415:Biomarkers; D053244:Osteoprotegerin; C506895:SPP1 protein, human; C506030:TNFRSF11B protein, human; D053495:Osteopontin
keywords: Cardiovascular autonomic nerve function; Osteopontin; Osteoprotegerin; Parasympathetic nerve function; Type 2 diabetes mellitus