A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long-term follow-up cohort.

Background: Osteocalcin (OC), an osteoblast-specific protein, has been demonstrated to affect glucose metabolism in both animals and humans. Studies in animals have shown an effect of undercarboxylated OC (ucOC) on beta-cell proliferation and insulin resistance. It remains unclear whether OC is associated with the future development of diabetes in humans, as well as the relative importance of ucOC vs OC.

Objective: The aim of this study was to examine serum OC and its post-translational forms as potential biomarkers for future the development of type 2 diabetes.

Methods: This was a nested case-control study using data from the Electricity Generating Authority of Thailand (EGAT). We identified 63 men without diabetes in the exploratory cohort at baseline who developed type 2 diabetes (DM) during the 10-year follow-up period from 1998-2008, and also 63 men age- and BMI-matched for a non-diabetes control group (non-DM). Serum N-mid OC and ucOC were measured in baseline blood samples. Logistic regression models were used to explore and identify baseline factors, including OC and ucOC, that predicted the subsequent development of diabetes.

Results: The mean age and BMI were similar in both non-DM and DM groups (47·2 ± 0·5 vs 47·8 ± 0·8 years and 25·2 ± 0·5 vs 25·9 ± 0·5 kg/m(2) , respectively). Only baseline mean serum N-mid OC (15·2 ± 0·5 vs 13·0 ± 0·5 μg/l, P < 0·05) and fasting plasma glucose (4·92 ± 0·04 vs 5·28 ± 0·07 mmol/l, P < 0·05) were significantly different between the two groups. Multiple logistic regression analysis showed that baseline serum N-mid OC and glucose, but not ucOC, were independent risk factors for the development of diabetes in this long-term study cohort.

Conclusions: Circulating total OC is associated with incident diabetes in men. Further studies to evaluate the potential utility of OC as a biomarker to predict the development of type 2 diabetes are warranted.