Sclerostin in type 1 diabetes mellitus: gender differences and associations with clinical features, bone mass and metabolism

SOST gene product, sclerostin, is an osteocyte derived glycoprotein which works as inhibitor of the Wnt/βCatenin signaling, a critical pathway for osteoblast proliferation and activity. Published data on sclerostin levels 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; 51% females) were consecutively enrolled in this study and evaluated for the presence of diabetic related complications (i.e. macrovascular disease, sensory-motor neuropathy, nephropathy, retinopathy). Data regarding duration of disease, total daily insulin requirements, therapeutic schemes (continuous subcutaneous insulin infusion system or multiple daily injections) alcohol use, smoking status and level of 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. We found that D-PYR and sclerostin were significantly higher in women in comparison to men (P=0.04). In the whole study population, 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 observed between QUS parameters, BMI and OH-PRO. Sclerostin serum levels correlated with homocysteine (r=−0.34; P=0.005) and vitamin B12 (r=−0.31; P=0.02). 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. For the first time, we found that the presence of macroangiopathy in subjects with T1DM was an independent predictor of sclerostin levels, suggesting a possible role for sclerostin in vascular pathophysiology. These findings are in line with recent reports in subjects with type 2 diabetes mellitus, showing an association between circulating sclerostin and surrogate markers of atherosclerotic disease such as abnormal carotid intima-media thickness, carotid plaques and aortic calcifications.