The relationship between inhibitors of the Wnt signalling pathway (sclerostin and Dickkopf-1) and carotid intima-media thickness in postmenopausal women with type 2 diabetes mellitus

Diab Vasc Dis Res. 2014 Jan;11(1):48-52. doi: 10.1177/1479164113510923. Epub 2013 Nov 12.

Abstract

The aim of the study was to investigate the association of the extracellular inhibitors of Wnt/β-catenin signalling sclerostin and Dickkopf-1 (Dkk-1) with carotid intima-media thickness (CIMT) in type 2 diabetes mellitus (T2DM). We performed a cross-sectional study including 40 T2DM postmenopausal women and 40 healthy controls. CIMT was measured by B-mode ultrasound. Serum sclerostin and Dkk-1 were measured by solid-phase enzyme-linked immunosorbent assay (ELISA). Serum sclerostin and Dkk-1 concentrations were significantly higher in T2DM group than in controls. There was a significant negative correlation between sclerostin and Dkk-1 and CIMT in T2DM (p = 0.0063 and p = 0.0017, respectively). After adjustment for potential confounders, associations remained significant only for sclerostin. These data suggest that sclerostin, an established modulator of the canonical Wnt signalling, may protect against progression of vascular complications in diabetic patients, possibly by attenuating upregulation of β-catenin activity in the vascular cells.

Keywords: CIMT; Dkk-1; Sclerostin; type 2 diabetes.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Aged
  • Allostasis
  • Atherosclerosis / complications*
  • Atherosclerosis / diagnostic imaging
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Bone Morphogenetic Proteins / blood*
  • Bone Morphogenetic Proteins / metabolism
  • Carotid Arteries / diagnostic imaging
  • Carotid Intima-Media Thickness*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / diagnostic imaging*
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Markers
  • Humans
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Middle Aged
  • Postmenopause
  • Up-Regulation*
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Bone Morphogenetic Proteins
  • DKK1 protein, human
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • SOST protein, human
  • Wnt Proteins