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. 2021 Feb;10(2):131-138.
doi: 10.1530/EC-20-0535.

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

Anouar Aznou  1 , Rick Meijer  1 , Daniel van Raalte  1 , Martin den Heijer  1 , Annemieke Heijboer  2 , Renate de Jongh  1
Affiliations

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

Anouar Aznou et al. Endocr Connect. 2021 Feb.

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 affects serum sclerostin concentrations.

Design: A cross-sectional study.

Methods: Insulin sensitivity was measured in lean (BMI < 25 kg/m2) and obese (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 < 0.01). 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/min, P = 0.03 and 1.59 mg/kg/min, P = 0.50, respectively). Hyperinsulinaemia 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 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 hypothesis-generating and should be confirmed by additional studies.

Keywords: bone metabolism; hyperinsulinemic-euglycemic clamp; insulin; obesity; sclerostin; sensitivity.

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Figures

Figure 1
Figure 1
Corrected mean M-Value presented for serum sclerostin quartiles in obese (panel A) and lean women (panel B).
Figure 2
Figure 2
Univariate regression analysis of serum sclerostin with corrected M-value in obese women.
See this image and copyright information in PMC

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