Total and undercarboxylated osteocalcin predict changes in insulin sensitivity and β cell function in elderly men at high cardiovascular risk

Am J Clin Nutr. 2012 Jan;95(1):249-55. doi: 10.3945/ajcn.111.016642. Epub 2011 Dec 14.


Background: Osteocalcin has been related to insulin secretion in experimental models. Few prospective studies have evaluated the association between circulating osteocalcin concentrations and insulin secretion and sensitivity in humans.

Objective: The objective was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin and insulin secretion and sensitivity in elderly men at high cardiovascular risk.

Design: We examined cross-sectional and longitudinal associations between serum measurements of total osteocalcin and undercarboxylated osteocalcin (ucOC) with fasting glucose, fasting insulin, HOMA-IR, and HOMA β cell function (HOMA-BCF) in 79 elderly men. We also examined the association between 2-y changes in osteocalcin and changes in fasting glucose, insulin, HOMA-IR, and HOMA-BCF.

Results: In an adjusted multivariable linear regression analysis, increases in serum osteocalcin were significantly associated with an increase in HOMA-BCF (β coefficient: 2.87; 95% CI: 0.23, 5.52; P = 0.033), and changes in ucOC were linked to a decrease in HOMA-IR (β coefficient: -0.31; 95% CI: -0.60, 0.03; P = 0.032). Moreover, in subjects not taking oral antidiabetic drugs, baseline osteocalcin concentrations were positively associated with higher fasting insulin concentrations and HOMA-BCF even after adjustment for BMI, physical activity, intervention group, presence of type 2 diabetes mellitus, and baseline values of each dependent variable.

Conclusions: Changes in serum osteocalcin and ucOC are associated with an improvement in insulin secretion and sensitivity, which suggests a possible role of bone in the development of type 2 diabetes. This trial is registered at as ISRCTN35739639.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology
  • Cross-Sectional Studies
  • Humans
  • Insulin / blood*
  • Insulin Resistance / physiology*
  • Insulin-Secreting Cells / physiology*
  • Linear Models
  • Longitudinal Studies
  • Male
  • Multivariate Analysis
  • Osteocalcin / blood*
  • Risk Factors


  • Biomarkers
  • Blood Glucose
  • Insulin
  • Osteocalcin

Associated data

  • ISRCTN/ISRCTN35739639