Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women
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 hyperinsulinemia affects serum sclerostin concentrations. Design A cross-sectional study. Methods Insulin sensitivity was measured in lean (BMI<25 kg·m-2) and obese (BMI > 30 kg·m-2) women using a hyperinsulinemic-euglycemic 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·m-2, respectively. Obese women had higher serum sclerostin than lean women (122±33 vs 93±33 nmol/L, p<0.01). Higher serum sclerostin was associated with lower insulin sensitivity in obese, but not in lean individuals (difference in M value between highest and lowest quartile: -7.02 mg⋅kg−1⋅min−1, p = 0.03 and 1.59 mg⋅kg−1⋅min−1, p = 0.50, respectively). Hyperinsulinemia did not affect serum sclerostin in lean nor obese women (p>0.5). Conclusion Serum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinemic euglycemic 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 hypothesis-generating and should be confirmed by additional studies.