Sclerostin Levels Associated with Inhibition of the Wnt/β-Catenin Signaling and Reduced Bone Turnover in Type 2 Diabetes Mellitus

Context: Patients with type 2 diabetes (T2DM) have low bone turnover, poor bone quality, and circulating levels of sclerostin significantly higher than non-T2DM controls. There are no data on the possible association of sclerostin with beta-catenin, a key component of the Wnt/beta-catenin canonical signaling. Objectives: The aim of the study was to evaluate the circulating beta-catenin levels in T2DM patients and to analyze their relationship with sclerostin and bone turnover markers. Design: This was a cross-sectional study. Setting and Patients: The study was conducted at a clinical research center. Forty T2DM postmenopausal women were studied and compared with 40 healthy controls. Bone status was assessed by dual-energy x-ray absorptiometry measurements (bone mineral density) and by measuring bone alkaline phosphatase and carboxy-terminal telopeptide of type 1 collagen. Sclerostinand beta-catenin were evaluated by an immunoenzymetric assay. Results: Consistent with previous reports in T2DM subjects, we found sclerostin levels higher and bone turnover markers lower than controls. In our cohort of T2DM patients, beta-catenin levels are significantly lower than in controls (median 1.22 pg/ml, 25th to 75th percentiles 0.50-2.80; and median 4.25 pg/ml, 25th to 75th percentiles 2.20-7.62, respectively; P = 0.0002). beta-Catenin correlated negatively with sclerostin (P < 0.0001) and positively with bone alkaline phosphatase (P = 0.0030) only in T2DM patients and negatively with age in both groups. Eight of the 40 T2DM patients had vertebral fractures. Conclusions: These results show for the first time that T2DM patients have serum concentrations of beta-catenin lower than controls. The negative association of beta-catenin with sclerostin suggests a biological effect of increased sclerostin on the Wnt signaling, which appears impaired in T2DM. (J Clin Endocrinol Metab 97: 3744-3750, 2012)