title: Atherosclerotic disease in type 2 diabetes is associated with an increase in sclerostin levels.
abstract: OBJECTIVE
  Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years).
  
  
  RESULTS
  Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥ 42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT (P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561-2.586], P = 0.003) and IMT (β = 0.330 [14.237-67.693], P = 0.003) were positively correlated with sclerostin.
  
  
  CONCLUSIONS
  Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients.
authors.affiliation: Bone Metabolic Unit, Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad, Endocrinology Division, Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Morales-Santana
authors.forename: Beatriz
authors.initials: B
authors.lastname: García-Fontana
authors.forename: Antonia
authors.initials: A
authors.lastname: García-Martín
authors.forename: Pedro
authors.initials: P
authors.lastname: Rozas-Moreno
authors.forename: José Antonio
authors.initials: JA
authors.lastname: García-Salcedo
authors.forename: Rebeca
authors.initials: R
authors.lastname: Reyes-García
authors.forename: Manuel
authors.initials: M
authors.lastname: Muñoz-Torres
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D050197:Atherosclerosis / Q000097:blood*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human