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Anouar Aznou, Rick I. Meijer, Dani�l H van Raalte, Martin den Heijer, Annemieke C Heijboer, and Renate T De Jongh

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.