|Shea, M Kyla - JM USDA HNRCA @ TUFTS|
|Gundberg, Caren - YALE SCHOOL OF MEDICINE|
|Meigs, James - MASS GENERAL HOSPITAL|
|Yoshida, Makikol - JM USDA HNRCA @ TUFTS|
Submitted to: American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 20, 2009
Publication Date: November 1, 2009
Citation: Shea, M., Gundberg, C., Meigs, J., Dallal, G., Saltzman, E., Yoshida, M., Jacques, P., Booth, S.L. 2009. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. American Journal of Clinical Nutrition. 90(5):1230-1235. Interpretive Summary: Osteocalcin is a protein synthesized in bone, where it is activated by vitamin K. Osteocalcin circulates in both the active and inactive forms. Recent cell and animal studies show the inactive form of osteocalcin can improve insulin sensitivity, suggesting that bone tissue may influence glucose and insulin metabolism. Since there are currently no studies that have examined the association between inactive osteocalcin and insulin resistance in humans, we tested the associations between the blood concentrations of three forms of osteocalcin: inactive, active, and total (which is the sum of the inactive and active forms) and insulin resistance in older non-diabetic men and women. Among the participants in our study, the concentration of inactive osteocalcin in blood was not associated with insulin resistance. However, increased concentrations of both active osteocalcin and total osteocalcin were associated with improved insulin resistance, which suggest that osteocalcin is a protein that may link bone to glucose metabolism in humans.
Technical Abstract: Context: The uncarboxylated form of osteocalcin (OC), a protein synthesized in bone, may influence glucose and insulin metabolism. Objective: Our purpose was to examine the cross-sectional associations between circulating ucOC and measures of insulin resistance and inflammation in humans. Design , Setting, and Participants: The uncarboxylated fraction of OC (ucOC) and total OC were measured in serum of 344 healthy, non-diabetic men and women ages 60-80 yrs (58% F) prior to participation in a clinical trial to study the influence of vitamin K supplementation on bone loss. Carboxylated OC (cOC) and the percent of uncarboxylated OC (%ucOC) were calculated from the measures of ucOC and total OC. Main Outcome Measures: Homeostasis model (HOMA-IR) was calculated from fasting plasma insulin and glucose measures at the baseline. Interleukin-6 (IL-6), C-reactive protein (CRP), and adiponectin were also measured. Results: UcOC and %ucOC were not associated with insulin resistance in older adults. However, total OC and cOC were inversely associated with HOMA-IR (p=0.004), and with fasting insulin (p = 0.03). Adiponectin, which was inversely associated with ucOC, cOC and total OC (all p <0.01), attenuated associations between cOC and total OC with HOMA-IR. UcOC and total OC were inversely associated with IL-6 and CRP (p<0.001); these associations were not explained by adiponectin. Conclusions: In older men and women, the uncarboxylated fraction of OC in circulation was not associated with insulin resistance. However, elevated cOC and total OC were associated with improved insulin resistance, supporting a link between skeletal physiology and insulin metabolism in humans.