title: Association of plasma osteoprotegerin and adiponectin with arterial function, cardiac function and metabolism in asymptomatic type 2 diabetic men.
abstract: BACKGROUND
  Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor superfamily, is linked to cardiovascular disease. Negative associations exist between circulating OPG and cardiac function. The adipocytokine adiponectin (ADPN) is downregulated in type 2 diabetes mellitus (T2DM) and coronary artery disease and shows an inverse correlation with insulin sensitivity and cardiovascular disease risk. We assessed the relationship of plasma OPG and ADPN and arterial function, cardiac function and myocardial glucose metabolism in T2DM.
  
  
  METHODS
  We included 78 asymptomatic men with uncomplicated, well-controlled T2DM, without inducible ischemia, assessed by dobutamine-stress echocardiography, and 14 age-matched controls. Cardiac function was measured by magnetic resonance imaging, myocardial glucose metabolism (MMRglu) by 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography. OPG and ADPN levels were measured in plasma.
  
  
  RESULTS
  T2DM patients vs. controls showed lower aortic distensibility, left ventricular (LV) volumes, impaired LV diastolic function and MMRglu (all P < 0.05). In T2DM men vs. controls, OPG levels were higher (P = 0.02), whereas ADPN concentrations were decreased (P = 0.04). OPG correlated inversely with aortic distensibility, LV volumes and E/A ratio (diastolic function), and positively with LV mass/volume ratio (all P < 0.05). Regression analyses showed the associations with aortic distensibility and LV mass/volume ratio to be independent of age-, blood pressure- and glycated hemoglobin (HbA1c). However, the associations with LV volumes and E/A ratio were dependent of these parameters. ADPN correlated positively with MMRglu (P < 0.05), which, in multiple regression analysis, was dependent of whole-body insulin sensitivity, HbA1c and waist.
  
  
  CONCLUSIONS
  OPG was inversely associated with aortic distensibility, LV volumes and LV diastolic function, while ADPN was positively associated with MMRglu. These findings indicate that in asymptomatic men with uncomplicated T2DM, OPG and ADPN may be markers of underlying mechanisms linking the diabetic state to cardiac abnormalities.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN53177482.
authors.affiliation: Diabetes Center/Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands. j.chen@vumc.nl
authors.forename: Weena J Y
authors.initials: WJ
authors.lastname: Chen
authors.forename: Luuk J
authors.initials: LJ
authors.lastname: Rijzewijk
authors.forename: Rutger W
authors.initials: RW
authors.lastname: van der Meer
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.forename: Eelco
authors.initials: E
authors.lastname: van Duinkerken
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: Lammertsma
authors.forename: Hildo J
authors.initials: HJ
authors.lastname: Lamb
authors.forename: Albert
authors.initials: A
authors.lastname: de Roos
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Jan W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Jeroen J
authors.initials: JJ
authors.lastname: Bax
authors.forename: Mette
authors.initials: M
authors.lastname: Bjerre
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Michaela
authors.initials: M
authors.lastname: Diamant
mesh_terms: D052242:Adiponectin / Q000097:blood*; D001011:Aorta / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin / Q000097:blood*; D049268:Positron-Emission Tomography; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D005947:Glucose; D006442:Glycated Hemoglobin; D053244:Osteoprotegerin