Sclerostin May Play Role in Insulin Resistance

Share this content:
Sclerostin May Play Role in Insulin Resistance
Sclerostin May Play Role in Insulin Resistance

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.”

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.

Reference

  1. Daniele G et al. Diabetes Care. 2015;doi:10.2337/dc14-2989.
You must be a registered member of Endocrinology Advisor to post a comment.

Sign Up for Free e-Newsletters

CME Focus