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Sclerostin levels not associated with type 2 diabetes risk
The risk for type 2 diabetes is not significantly associated with sclerostin levels, but weak correlations exist between sclerostin and fasting glucose and insulin levels and homeostasis model of assessment for insulin resistance, according to study results.
Oriana Hoi Yun Yu, MD, MSc, of the Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital and the division of endocrinology, Jewish General Hospital in Montreal, and colleagues evaluated data from the population-based Canadian Multicentre Osteoporosis Study on 1,778 adults (mean age, 63.2 years) with no history of type 2 diabetes. Researchers sought to determine whether sclerostin levels are associated with fasting glucose and insulin levels, insulin resistance or the risk for type 2 diabetes. Follow-up was conducted until Dec. 31, 2013, diagnosis of type 2 diabetes or death (median, 7.5 years).
Researchers observed a weak relationship between sclerostin levels and fasting glucose (P < .05) and insulin levels (P < .05) and homeostasis model of assessment for insulin resistance (HOMA-IR; P = .02). After adjustment for covariables, there was no longer a significant relationship between sclerostin and fasting glucose level (P = .97). However, sclerostin levels were associated with fasting insulin (P < .0001) and HOMA-IR (P < .0001) on multiple linear regression analysis.
Through follow-up, there was a rate of type 2 diabetes of 7.7 per 1,000 person-years.
In the primary analyses, No significant relationships were observed between sclerostin levels and the risk for incident type 2 diabetes (HR = 1.3; 95% CI, 0.37-4.57).
“This study demonstrated that sclerostin levels are not conclusively associated with the risk of incident type 2 diabetes, but showed a significant association between fasting insulin levels and sclerostin, suggesting a possible link between glucose metabolism, insulin resistance and the sclerostin pathway,” the researchers wrote. “Further studies are required to assess the directionality of effect to determine whether glucose metabolism and sclerostin are causally related.” – by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
Perspective
Back to TopWithin the study cohort, almost 3,000 individuals had sclerostin measured. The participants who reported a diagnosis of type 2 diabetes or use of an antidiabetic agent at the time when sclerostin was measured were excluded from the study. Furthermore, due to the lack of HbA1c measurements in the study, biochemical tests were not employed to identify participants who had diabetes. Consistent with previous reports in IFG/IGT and type 2 diabetes, sclerostin levels were increased approximately 25% in patients with type 2 diabetes (Daniele G, et al. Diabetes Care. 2015;doi: 10.2337/dc14-2989. Garcia-Martin. J Clin Endocrinol Metab. 2012;doi: 10.1210/jc.2011-2186). After excluding 910 participants who were lost at follow-up, a total of 1,778 nondiabetic individuals were examined. Although there was no significant association between sclerostin levels and the risk for incident type 2 diabetes (self-reported or diabetes treatment), there was a significant association between sclerostin and fasting insulin or HOMA-IR, also consistent with our previous studies. We believe that also these data in humans are somehow consistent with the concept that sclerostin might play a role in glucose metabolism, possibly in concert with other bone-derived factors, which might thus become targets for new glucose-lowering drugs.