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

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.

Sclerostin distribution in children and adolescents with type 1 diabetes mellitus and correlation with bone metabolism and bone mineral density

“…In agreement with this study, comparable sclerostin values between patients and controls, were also observed in two adult T1DM studies , whereas one study demonstrated higher sclerostin values in adult T1DM patients. In adult T2DM studies sclerostin levels were constantly reported higher in patients than controls . In these studies sclerostin was higher in men , positively associated with chronological age and disease duration , while positive association or absent association with BMI was found.…”

Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus

“…These data may account for an increased cardiovascular risk in men in comparison with women with T1DM. In addition, our results seem to be in line with a recent report showing that, in T2DM postmenopausal women, sclerostin was negatively associated with IMT, and was an independent predictor of IMT in multivariate linear regression analysis (40). Taken together with our findings, these evidences suggest that sclerostin may be involved in the delay of atherosclerosis progression.…”

Sclerostin is expressed in the atherosclerotic plaques of patients who undergoing carotid endarterectomy

“…16 In a cross-sectional study conducted in patients with T2D, higher levels of SC were observed in subjects with concomitant atherosclerotic disease compared with subjects without atherosclerotic lesions. 12 In contrast, a negative correlation was observed between serum SC and carotid intima-media thickness in women with T2D 17 and in Afro-American men with T2D and calcified atherosclerotic plaques. 18 These findings suggest a possible role of SC in the development of atherosclerosis in patients with T2D, although the specific function of SC remains to be elucidated.…”