Top

Journal of Endocrinological Investigation

Published in:

01-07-2014 | Original Article

Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes

Authors: Ernesto Maddaloni, Luca D’Onofrio, Angelo Lauria, Anna Rita Maurizi, Rocky Strollo, Andrea Palermo, Nicola Napoli, Silvia Angeletti, Paolo Pozzilli, Silvia Manfrini

Published in: Journal of Endocrinological Investigation | Issue 7/2014

Abstract

Purpose

Diabetic osteopathy is an upcoming complication of diabetes characterized by osteoporosis, increased risk for bone fractures and alterations in bone metabolism. Osteocalcin (OC) is a bone-specific protein produced by osteoblasts involved in the regulation of glucose and energy metabolism. The aim of this study is to determine whether OC serum levels are correlated with metabolic control in adult subjects with type one diabetes mellitus (T1DM).

Methods

A cross-sectional study was conducted on 93 subjects (51 men) with mean age, disease duration and body mass index (BMI) of 39.9 ± 12.3, 17.2 ± 12.6 years and 24.5 ± 3.4 kg/m², respectively. Blood samples were drawn to measure levels of hemoglobin A1c (HbA1c), OC, 25-OH vitamin D and PTH.

Results

Significant inverse correlations were found between OC and HbA1c (r = −0.295, P = 0.004) and between OC and BMI (r = −0.218, P = 0.037). These correlations were confirmed also among men in the analyses by gender [HbA1c vs OC: r = −0.363, P = 0.009; BMI vs OC: r = −0.291, P = 0.043], and similar but nonsignificant trends were confirmed among women. A significant difference in mean OC was also found between the lowest and the highest HbA1c tertile (22.3 ± 10.0 vs 16.9 ± 8.0 ng/mL, P = 0.025).

Conclusions

These data show that in T1DM of long duration, OC serum levels are inversely associated with HbA1c and BMI, supporting the hypothesis that a poor glycemic control can affect osteoblast function.

International Diabetes Federation Guidelines (2011) Diabetes in childhood and adolescence

Gunczler P, Lanes R, Paz-Martinez V et al (1998) Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. J Pediatr Endocrinol Metab 11:413–419PubMedCrossRef

Hoang QQ, Sicheri F, Howard AJ, Yang DSC (2003) Bone recognition mechanism of porcine osteocalcin from crystal structure. Nature 425:977–980. doi:10.1038/nature02079 PubMedCrossRef

Dowd TL, Rosen JF, Li L, Gundberg CM (2003) The three-dimensional structure of bovine calcium ion-bound osteocalcin using 1H NMR spectroscopy. Biochemistry 42:7769–7779. doi:10.1021/bi034470s PubMedCrossRef

Hauschka PV, Carr SA (1982) Calcium-dependent alpha-helical structure in osteocalcin. Biochemistry 21:2538–2547PubMedCrossRef

Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 105:5266–5270. doi:10.1073/pnas.0711119105 PubMedCentralPubMedCrossRef

Lee NK, Sowa H, Hinoi E et al (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469. doi:10.1016/j.cell.2007.05.047 PubMedCentralPubMedCrossRef

Kindblom JM, Ohlsson C, Ljunggren O et al (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791. doi:10.1359/jbmr.081234 PubMedCrossRef

Lee YJ, Lee H, Jee SH et al (2010) Serum osteocalcin is inversely associated with adipocyte-specific fatty acid-binding protein in the Korean metabolic syndrome research initiatives. Diabetes Care 33:e90. doi:10.2337/dc10-0071 PubMedCrossRef

10.

Pittas AG, Harris SS, Eliades M et al (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832. doi:10.1210/jc.2008-1422 PubMedCentralPubMedCrossRef

11.

Saleem U, Mosley TH, Kullo IJ (2010) Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 30:1474–1478. doi:10.1161/ATVBAHA.110.204859 PubMedCentralPubMedCrossRef

12.

Hwang Y-C, Jeong I-K, 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. Diabetes Metab Res Rev 25:768–772. doi:10.1002/dmrr.1045 PubMedCrossRef

13.

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 94:45–49. doi:10.1210/jc.2008-1455 PubMedCrossRef

14.

Im J-A, Yu B-P, Jeon JY, Kim S-H (2008) Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 396:66–69. doi:10.1016/j.cca.2008.07.001 PubMedCrossRef

15.

Bao Y-Q, Zhou M, Zhou J et al (2011) Relationship between serum osteocalcin and glycaemic variability in type 2 diabetes. Clin Exp Pharmacol Physiol 38:50–54. doi:10.1111/j.1440-1681.2010.05463.x PubMedCrossRef

16.

Prats-Puig A, Mas-Parareda M, Riera-Pérez E et al (2010) Carboxylation of osteocalcin affects its association with metabolic parameters in healthy children. Diabetes Care 33:661–663. doi:10.2337/dc09-1837 PubMedCentralPubMedCrossRef

17.

Pollock NK, Bernard PJ, Wenger K et al (2010) Lower bone mass in prepubertal overweight children with prediabetes. J Bone Miner Res 25:2760–2769. doi:10.1002/jbmr.184 PubMedCentralPubMedCrossRef

18.

Maggio ABR, Ferrari S, Kraenzlin M et al (2010) Decreased bone turnover in children and adolescents with well controlled type 1 diabetes. J Pediatr Endocrinol Metab 23:697–707PubMedCrossRef

19.

Pater A, Sypniewska G, Pilecki O (2010) Biochemical markers of bone cell activity in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 23:81–86PubMedCrossRef

20.

Thrailkill KM, Jo C-H, Cockrell GE et al (2012) Determinants of undercarboxylated and carboxylated osteocalcin concentrations in type 1 diabetes. Osteoporos Int 23:1799–1806. doi:10.1007/s00198-011-1807-7 PubMedCentralPubMedCrossRef

21.

Napoli N, Strollo R, Pitocco D et al (2013) Effect of calcitriol on bone turnover and osteocalcin in recent-onset type 1 diabetes. PLoS One 8:e56488. doi:10.1371/journal.pone.0056488 PubMedCentralPubMedCrossRef

22.

Motyl KJ, McCabe LR, Schwartz AV (2010) Bone and glucose metabolism: a two-way street. Arch Biochem Biophys 503:2–10. doi:10.1016/j.abb.2010.07.030 PubMedCentralPubMedCrossRef

23.

Hofbauer LC, Brueck CC, Singh SK, Dobnig H (2007) Osteoporosis in patients with diabetes mellitus. J Bone Miner Res 22:1317–1328. doi:10.1359/jbmr.070510 PubMedCrossRef

24.

Ma L, Oei L, Jiang L et al (2012) Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol 27:319–332. doi:10.1007/s10654-012-9674-x PubMedCentralPubMedCrossRef

25.

Melton LJ, Riggs BL, Leibson CL et al (2008) A bone structural basis for fracture risk in diabetes. J Clin Endocrinol Metab 93:4804–4809. doi:10.1210/jc.2008-0639 PubMedCentralPubMedCrossRef

26.

Burghardt AJ, Issever AS, Schwartz AV et al (2010) High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 95:5045–5055. doi:10.1210/jc.2010-0226 PubMedCentralPubMedCrossRef

27.

Hadjidakis DJ, Raptis AE, Sfakianakis M et al (2006) Bone mineral density of both genders in type 1 diabetes according to bone composition. J Diabetes Complicat 20:302–307. doi:10.1016/j.jdiacomp.2005.07.006 PubMedCrossRef

28.

McCabe LR (2007) Understanding the pathology and mechanisms of type I diabetic bone loss. J Cell Biochem 102:1343–1357. doi:10.1002/jcb.21573 PubMedCrossRef

29.

Goh S-Y, Cooper ME (2008) Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93:1143–1152. doi:10.1210/jc.2007-1817 PubMedCrossRef

30.

Räkel A, Sheehy O, Rahme E, LeLorier J (2008) Osteoporosis among patients with type 1 and type 2 diabetes. Diabetes Metab 34:193–205. doi:10.1016/j.diabet.2007.10.008 PubMedCrossRef

31.

Conover CA, Lee PD, Riggs BL, Powell DR (1996) Insulin-like growth factor-binding protein-1 expression in cultured human bone cells: regulation by insulin and glucocorticoid. Endocrinology 137:3295–3301PubMed

32.

Thrailkill KM, Lumpkin CK, Bunn RC et al (2005) Is insulin an anabolic agent in bone? Dissecting the diabetic bone for clues. Am J Physiol Endocrinol Metab 289:E735–E745. doi:10.1152/ajpendo.00159.2005 PubMedCentralPubMedCrossRef

33.

Pozzilli P, Manfrini S, Crinò A et al (2005) Low levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in patients with newly diagnosed type 1 diabetes. Horm Metab Res 37:680–683. doi:10.1055/s-2005-870578 PubMedCrossRef

34.

Pitocco D, Crinò A, Di Stasio E et al (2006) The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset type 1 diabetes (IMDIAB XI). Diabet Med 23:920–923. doi:10.1111/j.1464-5491.2006.01921.x PubMedCrossRef

35.

Bizzarri C, Pitocco D, Napoli N et al (2010) No protective effect of calcitriol on beta-cell function in recent-onset type 1 diabetes: the IMDIAB XIII trial. Diabetes Care 33:1962–1963. doi:10.2337/dc10-0814 PubMedCentralPubMedCrossRef

36.

Kanazawa I, Yamaguchi T, Yamauchi M et al (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194. doi:10.1007/s00198-010-1184-7 PubMedCrossRef

37.

Iki M, Tamaki J, Fujita Y et al (2012) Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo osteoporosis risk in men (FORMEN) study. Osteoporos Int 23:761–770. doi:10.1007/s00198-011-1600-7 PubMedCrossRef

38.

Ducy P (2011) The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 54:1291–1297. doi:10.1007/s00125-011-2155-z PubMedCrossRef

39.

Gerdhem P, Isaksson A, Akesson K, Obrant KJ (2005) Increased bone density and decreased bone turnover, but no evident alteration of fracture susceptibility in elderly women with diabetes mellitus. Osteoporos Int 16:1506–1512. doi:10.1007/s00198-005-1877-5 PubMedCrossRef

40.

Chillaro JJ, Goday A, Flores-le-roux JA et al (2009) Estimated glucose disposal rate in assessment of the metabolic syndrome and microvascular complications in patients with type 1 diabetes. J Clin Endocrinol Metab 94:3530–3534. doi:10.1210/jc.2009-0960 CrossRef

41.

Ferron M, Wei J, Yoshizawa T et al (2010) An ELISA-based method to quantify osteocalcin carboxylation in mice. Biochem Biophys Res Commun 397:691–696. doi:10.1016/j.bbrc.2010.06.008 PubMedCentralPubMedCrossRef

42.

Ferron M, Wei J, Yoshizawa T et al (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308. doi:10.1016/j.cell.2010.06.003 PubMedCentralPubMedCrossRef

Title: Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes
Authors: Ernesto Maddaloni
Luca D’Onofrio
Angelo Lauria
Anna Rita Maurizi
Rocky Strollo
Andrea Palermo
Nicola Napoli
Silvia Angeletti
Paolo Pozzilli
Silvia Manfrini
Publication date: 01-07-2014
Publisher: Springer International Publishing
Published in: Journal of Endocrinological Investigation / Issue 7/2014
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-014-0092-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 7/2014

Esophagus motility in overt hypothyroidism

High prevalence of hypovitaminosis D in Sicilian children affected by growth hormone deficiency and its improvement after 12 months of replacement treatment

Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells

Characterization of skeletal parameters in a cohort of North Italian rugby players

Vitamin D supplementation: when and how?

Irisin in idiopathic foetal growth restriction

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials