Fibulin-1 is a marker for arterial extracellular matrix alterations in type 2 diabetes

Clin Chem. 2011 Nov;57(11):1556-65. doi: 10.1373/clinchem.2011.162966. Epub 2011 Sep 16.


Background: Extracellular matrix alterations are important elements in the arterial changes seen in diabetes, being associated with increased vascular stiffness and the development of cardiovascular diseases. However, no biomarkers for diabetes-related arterial changes have been defined.

Methods: Mammary artery specimens from 17 men with type 2 diabetes and 18 nondiabetic individuals were used for microarray expression profiling, quantitative real-time PCR, immunoassay, and immunohistochemical analyses. A derived candidate marker, fibulin-1, which is an elastin-associated matrix molecule, was measured immunochemically in plasma from (a) 70 patients scheduled for vascular surgery, (b) 305 patients with type 2 diabetes examined with carotid ultrasonography and echocardiography, and (c) 308 patients with type 2 diabetes, followed for 15 years.

Results: The most upregulated transcript in nonatherosclerotic arterial tissue from patients with type 2 diabetes encoded the extracellular matrix protein, fibulin-1. Higher concentrations of fibulin-1-protein were present in artery extracts from patients with diabetes than extracts from individuals without diabetes, and increased fibulin-1 immunostaining was apparent around the external elastic lamina of diabetic arteries. Patients with diabetes displayed increased plasma concentrations of fibulin-1 (P = 0.006). Plasma fibulin-1 concentrations correlated with hemoglobin A(1c) (P < 0.001), arterial stiffness indices including pulse pressure (P < 0.001), and carotid compliance (P = 0.004), as well as plasma N-terminal pro-B-type natriuretic peptide concentrations (P < 0.001) and were predictive of 15-year mortality (P = 0.013).

Conclusions: Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes.

Publication types

  • Validation Study

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Calcium-Binding Proteins / blood
  • Calcium-Binding Proteins / metabolism*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / mortality
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetes Mellitus, Type 2 / mortality
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoassay
  • Immunohistochemistry
  • Male
  • Mammary Arteries / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction


  • Biomarkers
  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • fibulin