SCLEROSTIN LEVELS IN TYPE 1 DIABETES MELLITUS: GENEDER DIFFERENCES AND ASSOCIATION WITH CLINICAL FEATURES

Sclerostin, is an osteocyte derived glycoprotein which works as inhibitor of the Wnt/β Catenin signaling, a critical pathway for osteoblast proliferation and activity. Published data on sclerostin in type 1 diabetes mellitus (T1DM) are few. The aims of our research were to investigate gender differences in sclerostin serum levels and the associations between sclerostin, bone mass, bone metabolism and the main clinical characteristics of subjects with T1DM. Sixty-nine T1DM Caucasian subjects (mean age 33.7±8.1) were consecutively enrolled in this study and evaluated for diabetic related complications (i.e. macrovascular disease, sensory-motor neuropathy, nephropathy, retinopathy). Data regarding duration of disease, daily insulin requirements, therapeutic schemes (continuous subcutaneous insulin infusion system or multiple daily injections) alcohol use, smoking status and physical activity were also collected. Bone mineral density was measured by quantitative ultrasound (QUS) at phalangeal site. Markers of bone resorption (urinary PYR, D-PYR, OH-PRO) and bone formation (serum B-ALP and BGP) were assessed in addition to sclerostin. DPYR and sclerostin were significantly higher in women in comparison to men (P=0.04). A disease duration greater than 15 years was associated to higher sclerostin levels (P=0.03). Bone turnover markers and QUS parameters were not correlated to sclerostin. A significant negative correlation was observ ed between QUS parameters, BMI and OH-PRO. A generalized linear model showed that macroangiopathy was the only predictor of sclerostin serum levels (beta=−11.8, 95%CI from −21.9 to −1.7; P=0.02). These results demonstrate that T1DM women exhibit higher sclerostin levels than men, and that circulating sclerostin is not associated with bone turnover markers and phalangeal QUS measurements. Macroangiopathy in subjects with T1DM was an independent predictor of sclerostin levels, suggesting a possible role for sclerostin in vascular pathophysiology.