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Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study

Esben Laugesen1*, Pernille Høyem1, Jens Sandahl Christiansen1, Søren Tang Knudsen1, Klavs Würgler Hansen2, W Scott Argraves3, Troels Krarup Hansen1, Per Løgstrup Poulsen1 and Lars Melholt Rasmussen4

Author Affiliations

1 Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Noerrebrogade 44, 8000 Aarhus C, Denmark

2 Medical Department, Diagnostic Center, Regional Hospital Silkeborg, Falkevej 1-3, 8600 Silkeborg, Denmark

3 Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC 29425, USA

4 Department of Clinical Biochemistry and Pharmacology, Institute of Molecular Medicine and Clinical Institute, University of Southern Denmark, Sdr. Boulevard 29, 5000 Odense, Denmark

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Cardiovascular Diabetology 2013, 12:107  doi:10.1186/1475-2840-12-107

Published: 18 July 2013



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.


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.


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.


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.

Type 2 diabetes mellitus; Arterial stiffness; Pulse wave velocity; Fibulin-1