title: Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.
abstract: BACKGROUND
  The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extracellular matrix protein, fibulin-1, was recently found in higher concentrations in the arterial wall and in plasma in patients with long duration type 2 diabetes. Furthermore, plasma fibulin-1 independently predicted total mortality and was associated with pulse pressure, an indirect measure of arterial stiffness. Whether plasma fibulin-1 is associated with arterial stiffness at earlier phases of type 2 diabetes has not been determined.
  
  
  METHODS
  In this cross-sectional study, we examined 90 patients with recently diagnosed type 2 diabetes (< 5 years) and 90 gender- and age-matched controls. Plasma fibulin-1 was measured immunochemically. Arterial stiffness was assessed by carotid-femoral Pulse Wave Velocity (PWV). Differences in means were assessed by t-tests. Associations were assessed by multivariate regression analyses.
  
  
  RESULTS
  Plasma fibulin-1 levels were lower in the diabetic group compared with the control group, 93 ± 28 vs 106 ± 30 μg/mL, p = 0.005. In unadjusted analysis of the total study sample, plasma fibulin-1 was not associated with PWV, p = 0.46. However, with adjustment for the confounders age, gender, mean blood pressure, heart rate, body mass index, diabetes and glomerular filtration rate, a 10 μg/mL increase in plasma fibulin was associated with 0.09 ± 0.04 m/s increase in PWV, p < 0.05. In subgroup analysis, plasma fibulin-1 was associated with PWV in the diabetes group, (0.16 ± 0.07 m/s increase in PWV per 10 μg/mL increase in plasma fibulin-1, p<0.05), but not controls, β = 0.021 ± 0.057 m/s per 10 μg/mL, p = 0.70. The association remained significant in the diabetes group after adjustment for covariates, p < 0.05.
  
  
  CONCLUSIONS
  Plasma fibulin-1 is independently associated with PWV. Yet, as the plasma level of fibulin-1 was lower in patients with recently diagnosed type 2 diabetes than in healthy controls, plasma fibulin-1 levels are not a simple marker of the degree of arterial stiffening. Further studies are needed to determine the exact role of fibulin-1 in arterial stiffness and cardiovascular risk in patients with type 2 diabetes.
authors.forename: Esben
authors.initials: E
authors.lastname: Laugesen
authors.forename: Pernille
authors.initials: P
authors.lastname: Høyem
authors.forename: Jens Sandahl
authors.initials: JS
authors.lastname: Christiansen
authors.forename: Søren Tang
authors.initials: ST
authors.lastname: Knudsen
authors.forename: Klavs Würgler
authors.initials: KW
authors.lastname: Hansen
authors.forename: W Scott
authors.initials: WS
authors.lastname: Argraves
authors.forename: Troels Krarup
authors.initials: TK
authors.lastname: Hansen
authors.forename: Per Løgstrup
authors.initials: PL
authors.lastname: Poulsen
authors.forename: Lars Melholt
authors.initials: LM
authors.lastname: Rasmussen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D002339:Carotid Arteries / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis* / Q000209:etiology* / Q000503:physiopathology; D005263:Femoral Artery / Q000503:physiopathology*; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D063177:Pulse Wave Analysis; D012307:Risk Factors; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; C060820:fibulin