In people with prediabetes, serum sclerostin appears to be higher. Moreover, researchers have observed a relationship between sclerostin and insulin resistance in skeletal muscle, liver and adipose tissue, according to data published in Diabetes Care.

“Bone has recently emerged as a new important organ in the regulation of glucose metabolism. Sclerostin, a 190-amino acid glycoprotein secreted mainly by osteocytes, is a circulating hormone that antagonizes the Wnt (Wingless-type mouse mammary tumor virus integration side) pathway, thus suppressing osteoblast activity and downregulating bone turnover,” the researchers wrote.

“Interestingly, a gene mutation in the Wnt signaling pathway has been associated with hyperlipidemia, hypertension, and early coronary artery disease in patients with metabolic syndrome.”

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However, the researchers noted, the link between sclerostin and insulin resistance has yet to be studied.

To explore this association, they conducted a cross-sectional study involving 43 healthy participants with normal glucose tolerance and 79 with impaired glucose regulation, including those with impaired fasting glucose, impaired glucose tolerance and a combination of the two. They underwent an oral glucose tolerance test (OGTT) and dual-energy X-ray absorptiometry (DXA).

Additionally, a subgroup of 18 participants with normal glucose tolerance and 30 with impaired glucose regulation underwent a euglycemic-hyperinsulinemic clamp with tracer.

Results revealed higher sclerostin levels among those with impaired glucose regulation vs. normal glucose tolerance (50.8 pmol/L vs. 38.7 pmol/L; P=.01).

The researchers observed a positive correlation between sclerostin and HOMA-IR (r=0.62; P<.001) and a negative correlation between sclerostin and insulin-mediated total body glucose disposal (r=–0.40; P<.001).

Data also showed a positive correlation between sclerostin and fasting endogenous glucose production and hepatic and adipose tissue insulin resistance indexes (r=0.48 and r=0.62; r=0.61; P<.001). Sclerostin levels were also inversely correlated with fasting and OGTT insulin clearance (r=–0.52 and r=–0.44, respectively; P<.001 for both).

The researchers, however, found no correlation between sclerostin levels and beta-cell function parameters.

In multiple linear regression analysis, adding sclerostin levels to traditional insulin resistance risk factors improved the r2 associated to HOMA-IR (r2 change: 0.055; F change: 28.893; P=.001) and insulin-mediated total body glucose disposal (r2 change: 0.059; F change: 4.938; P=.033).

“The correlation between sclerostin and insulin clearance at fasting state and during OGTT is novel; thus, studies are needed to explore the potential causal relationship,” the researchers wrote.


  1. Daniele G et al. Diabetes Care. 2015;doi:10.2337/dc14-2989.