Gamma-carboxylation of osteocalcin and insulin resistance in older men and women

Am J Clin Nutr. 2009 Nov;90(5):1230-5. doi: 10.3945/ajcn.2009.28151. Epub 2009 Sep 23.


Background: The skeletal protein osteocalcin is gamma-carboxylated by vitamin K. High serum uncarboxylated osteocalcin reflects low vitamin K status. In vitro and animal studies indicate that high uncarboxylated osteocalcin is associated with reduced insulin resistance. However, associations between osteocalcin and measures of insulin resistance in humans are less clear.

Objective: Our aim was to examine cross-sectional and longitudinal associations between circulating forms of osteocalcin (total, uncarboxylated, and carboxylated) and insulin resistance in older men and women.

Design: Cross-sectional associations between serum measures of total osteocalcin, carboxylated osteocalcin, and uncarboxylated osteocalcin and insulin resistance were examined in 348 nondiabetic men and women (mean age: 68 y; 58% female) by using the homeostasis model assessment of insulin resistance (HOMA-IR). Associations between each form of osteocalcin at baseline and 3-y change in HOMA-IR were examined in 162 adults (mean age: 69 y; 63% female) who did not receive vitamin K supplementation.

Results: Lower circulating uncarboxylated osteocalcin was not associated with higher HOMA-IR at baseline or at 3-y follow-up. Those in the lowest tertiles of total osteocalcin and carboxylated osteocalcin at baseline had higher baseline HOMA-IR (P = 0.006 and P = 0.02, respectively). The concentration of carboxylated osteocalcin at baseline was inversely associated with a 3-y change in HOMA-IR (P = 0.002).

Conclusions: In older adults, circulating uncarboxylated osteocalcin was not associated with insulin resistance. In contrast, elevated carboxylated osteocalcin and total osteocalcin were associated with lower insulin resistance, which supports a potential link between skeletal physiology and insulin resistance in humans. The role of vitamin K status in this association remains unclear and merits further investigation. This trial is registered at as NCT00183001.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adiponectin / blood
  • Aged
  • Blood Glucose / metabolism
  • Body Mass Index
  • Calcium / administration & dosage
  • Cholecalciferol / administration & dosage
  • Cross-Sectional Studies
  • Exercise
  • Female
  • Homeostasis
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Models, Biological
  • Osteocalcin / blood
  • Osteocalcin / metabolism*
  • Vitamin K 1 / administration & dosage
  • Vitamins / administration & dosage


  • Adiponectin
  • Blood Glucose
  • Insulin
  • Vitamins
  • Osteocalcin
  • Cholecalciferol
  • Vitamin K 1
  • Calcium

Associated data