Email updates

Keep up to date with the latest news and content from Cardiovascular Diabetology and BioMed Central.

Open Access Original investigation

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

For all author emails, please log on.

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

Published: 18 July 2013

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.

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