Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women

Abstract

Objective: The mechanisms underlying the development of peripheral insulin resistance are complex. Several studies have linked sclerostin, an osteocyte-derived inhibitor of the Wnt/β-catenin pathway, to obesity and insulin resistance. The aim of this study was to investigate (1) whether serum sclerostin is associated with insulin sensitivity in lean and/or obese women; and (2) whether hyperinsulinaemia affec ts serum sclerostin concentrations. Design: A cross-sectional study. Methods: Insulin sensitivity was measured in lean (BMI 30 kg/m2) women using a hyperinsulinaemic–euglycaemic clamp. Serum sclerostin was measured at baseline and during the clamp procedure. Results: We studied 21 lean and 22 obese women with a median age of 40 and 43 years and a median BMI of 22.4 and 33.5 kg/m2, respectively. Obese women had higher serum sclerostin than lean women (122 ± 33 vs 93 ± 33 nmol/L, P 0.5). Conclusion: Serum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinaemic–euglycaemic clamp in obese, but not lean women. This indicates a potential role of the Wnt/β-catenin pathway in regulating insulin sensitivity particularly in obese individuals. Our findings remain hypothesi s-generating and should be confirmed by additional studies.

Keywords

• sclerostin
• insulin
• sensitivity
• hyperinsulinemiceuglycemic clamp
• bone metabolism
• obesity