Atherosclerotic Disease in Type 2 Diabetes Is Associated With an Increase of Sclerostin Levels

  1. Manuel Muñoz-Torres, MD, PHD1
  1. 1Bone Metabolic Unit, Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF), Endocrinology Division, Hospital Universitario San Cecilio, Granada, Spain
  2. 2Proteomic Research Service, Fundación para la Investigación Biosanitaria de Andalucía Oriental-Alejandro Otero, Granada, Spain
  3. 3Endocrinology Division, Hospital General de Ciudad Real, Ciudad Real, Spain
  1. Corresponding author: Manuel Muñoz-Torres, mmt{at}


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).

RESEARCH DESIGN AND 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 positive 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.

  • Received August 30, 2012.
  • Accepted November 20, 2012.

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