Skip to main content
Top
Published in: Osteoporosis International 4/2012

Open Access 01-04-2012 | Original Article

Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level

Authors: Y.-C. Hwang, I.-K. Jeong, K.-J. Ahn, H.-Y. Chung

Published in: Osteoporosis International | Issue 4/2012

Login to get access

Abstract

Summary

In agreement with the results of animal studies, the plasma osteocalcin level is positively associated with improved glucose tolerance and insulin secretion and sensitivity. In addition, the plasma osteocalcin level is inversely associated with the development of diabetes; however, the plasma adiponectin level may not be involved in osteocalcin-mediated energy metabolism in humans.

Introduction

Recent animal studies have suggested crosstalk between bone and energy metabolism through osteocalcin. The aims of this study were to determine whether or not osteocalcin is associated with the improved glucose tolerance and insulin secretion and sensitivity, and whether or not the association is dependent on the plasma adiponectin level in humans.

Methods

Four hundred twenty-five subjects, 19–82 years of age (mean age, 53 years), were enrolled. An oral glucose tolerance test (OGTT) and OGTT-based methods that were validated against the euglycemic clamp were determined. Total osteocalcin, leptin, and total adiponectin levels were measured.

Results

The plasma levels of total osteocalcin were significantly different between the normal glucose tolerance, pre-diabetes, and diabetes groups. The glucose levels and homeostasis model assessment insulin resistance values varied inversely with the osteocalcin tertiles, and OGTT-based insulin secretion (HOMA-B%, disposition index) and insulin sensitivity indices (Stumvoll’s and OGIS indices) were increased with the tertiles. Although the plasma adiponectin level was positively correlated with the osteocalcin level, no changes in the association were noted between the plasma osteocalcin level and the glucose tolerance or insulin secretion and sensitivity indices after adjustment for the plasma adiponectin level. Based on multiple logistic regression analysis, the plasma osteocalcin level was inversely associated with the development of type 2 diabetes mellitus independent of age, gender, body mass index, and fasting plasma glucose and plasma adiponectin levels.

Conclusions

Circulating osteocalcin level is associated with improved glucose tolerance and insulin secretion and sensitivity independent of the plasma adiponectin level in humans.
Literature
1.
go back to reference Lee NK, Sowa H, Hinoi E et al (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469PubMedCrossRef Lee NK, Sowa H, Hinoi E et al (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469PubMedCrossRef
2.
go back to reference Im JA, Yu BP, Jeon JY, Kim SH (2008) Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 396:66–69PubMedCrossRef Im JA, Yu BP, Jeon JY, Kim SH (2008) Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 396:66–69PubMedCrossRef
3.
go back to reference Kanazawa I, Yamaguchi T, Yamamoto M et al (2009) Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:45–49PubMedCrossRef Kanazawa I, Yamaguchi T, Yamamoto M et al (2009) Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:45–49PubMedCrossRef
4.
go back to reference Zhou M, Ma X, Li H et al (2009) Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol 161:723–729PubMedCrossRef Zhou M, Ma X, Li H et al (2009) Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol 161:723–729PubMedCrossRef
5.
go back to reference Fernandez-Real JM, Izquierdo M, Ortega F et al (2009) The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 94:237–2459PubMedCrossRef Fernandez-Real JM, Izquierdo M, Ortega F et al (2009) The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 94:237–2459PubMedCrossRef
6.
go back to reference Kindblom JM, Ohlsson C, Ljunggren O et al (2008) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791CrossRef Kindblom JM, Ohlsson C, Ljunggren O et al (2008) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791CrossRef
7.
go back to reference Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832PubMedCrossRef Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832PubMedCrossRef
8.
go back to reference Hwang YC, Jeong IK, Ahn KJ, Chung HY (2009) The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diab Metab Res Rev 25:768–772CrossRef Hwang YC, Jeong IK, Ahn KJ, Chung HY (2009) The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diab Metab Res Rev 25:768–772CrossRef
9.
go back to reference Shea MK, Gundberg CM, Meigs JB et al (2009) Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 90:1230–1235PubMedCrossRef Shea MK, Gundberg CM, Meigs JB et al (2009) Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 90:1230–1235PubMedCrossRef
10.
go back to reference Winhofer Y, Handisurya A, Tura A et al (2010) Osteocalcin is related to enhanced insulin secretion in gestational diabetes. Diabetes Care 33:139–143PubMedCrossRef Winhofer Y, Handisurya A, Tura A et al (2010) Osteocalcin is related to enhanced insulin secretion in gestational diabetes. Diabetes Care 33:139–143PubMedCrossRef
11.
go back to reference Mari A, Ahrén B, Pacini G (2005) Assessment of insulin secretion in relation to insulin resistance. Curr Opin Clin Nutr Metab Care 8:529–533PubMedCrossRef Mari A, Ahrén B, Pacini G (2005) Assessment of insulin secretion in relation to insulin resistance. Curr Opin Clin Nutr Metab Care 8:529–533PubMedCrossRef
12.
go back to reference Pacini G, Mari A (2003) Methods for clinical assessment of insulin sensitivity and beta-cell function. Best Pract Res Clin Endocrinol Metab 17:305–322PubMedCrossRef Pacini G, Mari A (2003) Methods for clinical assessment of insulin sensitivity and beta-cell function. Best Pract Res Clin Endocrinol Metab 17:305–322PubMedCrossRef
13.
go back to reference Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRef Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22:1462–1470PubMedCrossRef
14.
go back to reference Stumvoll M, Mitrakou A, Pimenta W et al (2000) Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23:295–301PubMedCrossRef Stumvoll M, Mitrakou A, Pimenta W et al (2000) Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 23:295–301PubMedCrossRef
15.
go back to reference Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548PubMedCrossRef Mari A, Pacini G, Murphy E, Ludvik B, Nolan JJ (2001) A model-based method for assessing insulin sensitivity from the oral glucose tolerance test. Diabetes Care 24:539–548PubMedCrossRef
16.
go back to reference Ahren B, Pacini G (2004) Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess β cell function in clinical studies. Eur J Endocrinol 150:97–104PubMedCrossRef Ahren B, Pacini G (2004) Importance of quantifying insulin secretion in relation to insulin sensitivity to accurately assess β cell function in clinical studies. Eur J Endocrinol 150:97–104PubMedCrossRef
17.
go back to reference Muniyappa R, Lee S, Chen H, Quon MJ (2008) Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 294:E15–E26PubMedCrossRef Muniyappa R, Lee S, Chen H, Quon MJ (2008) Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab 294:E15–E26PubMedCrossRef
18.
go back to reference Gundberg CM, Looker AC, Nieman SD, Calvo MS (2002) Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 31:703–708PubMedCrossRef Gundberg CM, Looker AC, Nieman SD, Calvo MS (2002) Patterns of osteocalcin and bone specific alkaline phosphatase by age, gender, and race or ethnicity. Bone 31:703–708PubMedCrossRef
19.
go back to reference Ferron M, Wei J, Yoshizawa T et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308PubMedCrossRef Ferron M, Wei J, Yoshizawa T et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308PubMedCrossRef
20.
go back to reference Aonuma H, Miyakoshi N, Hongo M, Kasukawa Y, Shimada Y (2009) Low serum levels of undercarboxylated osteocalcin in postmenopausal osteoporotic women receiving an inhibitor of bone resorption. Tohoku J Exp Med 218:201–205PubMedCrossRef Aonuma H, Miyakoshi N, Hongo M, Kasukawa Y, Shimada Y (2009) Low serum levels of undercarboxylated osteocalcin in postmenopausal osteoporotic women receiving an inhibitor of bone resorption. Tohoku J Exp Med 218:201–205PubMedCrossRef
Metadata
Title
Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level
Authors
Y.-C. Hwang
I.-K. Jeong
K.-J. Ahn
H.-Y. Chung
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 4/2012
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-011-1679-x

Other articles of this Issue 4/2012

Osteoporosis International 4/2012 Go to the issue