Skip to main content
Erschienen in: Osteoporosis International 8/2013

01.08.2013 | Original Article

Serum osteocalcin levels are inversely associated with abdominal aortic calcification in men with type 2 diabetes mellitus

verfasst von: N. Ogawa-Furuya, T. Yamaguchi, M. Yamamoto, I. Kanazawa, T. Sugimoto

Erschienen in: Osteoporosis International | Ausgabe 8/2013

Einloggen, um Zugang zu erhalten

Abstract

Summary

We found that serum osteocalcin (OC) and undercarboxylated OC (ucOC) levels were negatively associated with abdominal aortic calcification in type 2 diabetes mellitus (T2DM) men. This finding suggests that circulating OC and ucOC are not only related to glucose or fat metabolism but also to arteriosclerosis.

Introduction

Recent studies revealed that serum osteocalcin levels were associated with not only bone metabolism but also glucose and fat metabolism. However, the relationship between serum OC levels and arteriosclerosis remains controversial. We examined whether or not bone metabolic markers including OC are associated with abdominal aortic calcification in patients with type 2 diabetes mellitus.

Methods

We recruited 118 men and 100 postmenopausal women with T2DM. We evaluated the abdominal aortic calcification score (ACS) on a lateral lumbar radiograph and examined the association between serum OC or undercarboxylated OC levels and ACS.

Results

The ACS of 3 and greater, which corresponded well to the highest quartile, was significantly and negatively associated with serum OC and ucOC levels in men by logistic regression analyses after adjusting for age, BMI, serum levels of creatinine and LDL cholesterol, radial bone mineral density, smoking, duration of DM, hemoglobin A1c, and the index of insulin resistance [odds ratio (OR) 0.36, 95 % confidence interval (CI) 0.19–0.70, P < 0.005, and OR 0.28, 95 % CI 0.12–0.69, P < 0.01, per standard deviation increase in OC and ucOC, respectively]. These observations were still significant after an additional adjustment for other bone markers. In contrast, there were no significant relationships with serum OC or ucOC levels and ACS in women.

Conclusions

These findings suggest that serum OC and ucOC levels are associated with not only bone metabolism but also arteriosclerosis in men, but not in women with type 2 diabetes mellitus.
Literatur
1.
Zurück zum Zitat Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed
2.
Zurück zum Zitat Price PA (1989) Gla-containing proteins of bone. Connect Tissue Res 21:51–57, discussion 57–60PubMedCrossRef Price PA (1989) Gla-containing proteins of bone. Connect Tissue Res 21:51–57, discussion 57–60PubMedCrossRef
3.
Zurück zum Zitat 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 U S A 105:5266–5270PubMedCrossRef 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 U S A 105:5266–5270PubMedCrossRef
4.
Zurück zum Zitat 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
5.
Zurück zum Zitat Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308PubMedCrossRef Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308PubMedCrossRef
6.
Zurück zum Zitat Fulzele K, Riddle RC, DiGirolamo DJ et al (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319PubMedCrossRef Fulzele K, Riddle RC, DiGirolamo DJ et al (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319PubMedCrossRef
7.
Zurück zum Zitat 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 94:237–245PubMedCrossRef 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 94:237–245PubMedCrossRef
8.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T (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, Yamauchi M, Kurioka S, Yano S, Sugimoto T (2009) Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:45–49PubMedCrossRef
9.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194PubMedCrossRef Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194PubMedCrossRef
10.
Zurück zum Zitat Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791PubMedCrossRef Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791PubMedCrossRef
11.
Zurück zum Zitat 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
12.
Zurück zum Zitat Fujishima M, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Yoshitake T (1996) Diabetes and cardiovascular disease in a prospective population survey in Japan: the Hisayama Study. Diabetes 45(Suppl 3):S14–16PubMed Fujishima M, Kiyohara Y, Kato I, Ohmura T, Iwamoto H, Nakayama K, Ohmori S, Yoshitake T (1996) Diabetes and cardiovascular disease in a prospective population survey in Japan: the Hisayama Study. Diabetes 45(Suppl 3):S14–16PubMed
13.
Zurück zum Zitat Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234PubMedCrossRef Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234PubMedCrossRef
14.
Zurück zum Zitat Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132:245–250PubMedCrossRef Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW (1997) New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 132:245–250PubMedCrossRef
15.
Zurück zum Zitat Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMed
16.
Zurück zum Zitat Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
17.
Zurück zum Zitat Price PA, Nishimoto SK (1980) Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci U S A 77:2234–2238PubMedCrossRef Price PA, Nishimoto SK (1980) Radioimmunoassay for the vitamin K-dependent protein of bone and its discovery in plasma. Proc Natl Acad Sci U S A 77:2234–2238PubMedCrossRef
18.
Zurück zum Zitat Nishimura J, Arai N, Tohmatsu J (2007) Measurement of serum undercarboxylated osteocalcin by ECLIA with the “Picolumi ucOC” kit. Clin Calcium 17:1702–1708PubMed Nishimura J, Arai N, Tohmatsu J (2007) Measurement of serum undercarboxylated osteocalcin by ECLIA with the “Picolumi ucOC” kit. Clin Calcium 17:1702–1708PubMed
19.
Zurück zum Zitat Ebrahim S, Papacosta O, Whincup P et al (1999) Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke 30:841–850PubMedCrossRef Ebrahim S, Papacosta O, Whincup P et al (1999) Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke 30:841–850PubMedCrossRef
20.
Zurück zum Zitat Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, Vita JA, Levy D, Benjamin EJ (2010) Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 121:505–511PubMedCrossRef Mitchell GF, Hwang SJ, Vasan RS, Larson MG, Pencina MJ, Hamburg NM, Vita JA, Levy D, Benjamin EJ (2010) Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation 121:505–511PubMedCrossRef
21.
Zurück zum Zitat O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22PubMedCrossRef O'Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22PubMedCrossRef
22.
Zurück zum Zitat Golestani R, Tio R, Zeebregts CJ, Zeilstra A, Dierckx RA, Boersma HH, Hillege HL, Slart RH (2010) Abdominal aortic calcification detected by dual X-ray absorptiometry: a strong predictor for cardiovascular events. Ann Med 42:539–545PubMedCrossRef Golestani R, Tio R, Zeebregts CJ, Zeilstra A, Dierckx RA, Boersma HH, Hillege HL, Slart RH (2010) Abdominal aortic calcification detected by dual X-ray absorptiometry: a strong predictor for cardiovascular events. Ann Med 42:539–545PubMedCrossRef
23.
Zurück zum Zitat Wilson PW, Kauppila LI, O'Donnell CJ, Kiel DP, Hannan M, Polak JM, Cupples LA (2001) Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation 103:1529–1534PubMedCrossRef Wilson PW, Kauppila LI, O'Donnell CJ, Kiel DP, Hannan M, Polak JM, Cupples LA (2001) Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality. Circulation 103:1529–1534PubMedCrossRef
24.
Zurück zum Zitat Wong ND, Lopez VA, Allison M, Detrano RC, Blumenthal RS, Folsom AR, Ouyang P, Criqui MH (2011) Abdominal aortic calcium and multi-site atherosclerosis: the Multiethnic Study of Atherosclerosis. Atherosclerosis 214:436–441PubMedCrossRef Wong ND, Lopez VA, Allison M, Detrano RC, Blumenthal RS, Folsom AR, Ouyang P, Criqui MH (2011) Abdominal aortic calcium and multi-site atherosclerosis: the Multiethnic Study of Atherosclerosis. Atherosclerosis 214:436–441PubMedCrossRef
25.
Zurück zum Zitat Bao Y, Zhou M, Lu Z, Li H, Wang Y, Sun L, Gao M, Wei M, Jia W (2011) Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol (Oxf) 75:196–201CrossRef Bao Y, Zhou M, Lu Z, Li H, Wang Y, Sun L, Gao M, Wei M, Jia W (2011) Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin Endocrinol (Oxf) 75:196–201CrossRef
26.
Zurück zum Zitat Zhang Y, Qi L, Gu W et al (2010) Relation of serum osteocalcin level to risk of coronary heart disease in Chinese adults. Am J Cardiol 106:1461–1465PubMedCrossRef Zhang Y, Qi L, Gu W et al (2010) Relation of serum osteocalcin level to risk of coronary heart disease in Chinese adults. Am J Cardiol 106:1461–1465PubMedCrossRef
27.
Zurück zum Zitat Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395PubMedCrossRef Pennisi P, Signorelli SS, Riccobene S, Celotta G, Di Pino L, La Malfa T, Fiore CE (2004) Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels. Osteoporos Int 15:389–395PubMedCrossRef
28.
Zurück zum Zitat Inaba M, Terada M, Koyama H, Yoshida O, Ishimura E, Kawagishi T, Okuno Y, Nishizawa Y, Otani S, Morii H (1995) Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells. J Bone Miner Res 10:1050–1056PubMedCrossRef Inaba M, Terada M, Koyama H, Yoshida O, Ishimura E, Kawagishi T, Okuno Y, Nishizawa Y, Otani S, Morii H (1995) Influence of high glucose on 1,25-dihydroxyvitamin D3-induced effect on human osteoblast-like MG-63 cells. J Bone Miner Res 10:1050–1056PubMedCrossRef
29.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2009) Adiponectin is associated with changes in bone markers during glycemic control in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:3031–3037PubMedCrossRef Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2009) Adiponectin is associated with changes in bone markers during glycemic control in type 2 diabetes mellitus. J Clin Endocrinol Metab 94:3031–3037PubMedCrossRef
30.
Zurück zum Zitat Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, Hata K, Fukumoto S, Matsumoto T (1997) Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 82:2915–2920PubMedCrossRef Okazaki R, Totsuka Y, Hamano K, Ajima M, Miura M, Hirota Y, Hata K, Fukumoto S, Matsumoto T (1997) Metabolic improvement of poorly controlled noninsulin-dependent diabetes mellitus decreases bone turnover. J Clin Endocrinol Metab 82:2915–2920PubMedCrossRef
31.
Zurück zum Zitat Harno E, Edwards G, Geraghty AR, Ward DT, Dodd RH, Dauban P, Faure H, Ruat M, Weston AH (2008) Evidence for the presence of GPRC6A receptors in rat mesenteric arteries. Cell Calcium 44:210–219PubMedCrossRef Harno E, Edwards G, Geraghty AR, Ward DT, Dodd RH, Dauban P, Faure H, Ruat M, Weston AH (2008) Evidence for the presence of GPRC6A receptors in rat mesenteric arteries. Cell Calcium 44:210–219PubMedCrossRef
32.
Zurück zum Zitat Montalcini T, Emanuele V, Ceravolo R, Gorgone G, Sesti G, Perticone F, Pujia A (2004) Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women. Am J Cardiol 94:266–269PubMedCrossRef Montalcini T, Emanuele V, Ceravolo R, Gorgone G, Sesti G, Perticone F, Pujia A (2004) Relation of low bone mineral density and carotid atherosclerosis in postmenopausal women. Am J Cardiol 94:266–269PubMedCrossRef
33.
Zurück zum Zitat Parker BD, Bauer DC, Ensrud KE, Ix JH (2010) Association of osteocalcin and abdominal aortic calcification in older women: the study of osteoporotic fractures. Calcif Tissue Int 86:185–191PubMedCrossRef Parker BD, Bauer DC, Ensrud KE, Ix JH (2010) Association of osteocalcin and abdominal aortic calcification in older women: the study of osteoporotic fractures. Calcif Tissue Int 86:185–191PubMedCrossRef
34.
Zurück zum Zitat Oury F, Sumara G, Sumara O et al (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809PubMedCrossRef Oury F, Sumara G, Sumara O et al (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809PubMedCrossRef
35.
Zurück zum Zitat Kanazawa I, Tanaka K, Ogawa N, Yamauchi M, Yamaguchi T, Sugimoto T (2012) Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus. Osteoporos Int Kanazawa I, Tanaka K, Ogawa N, Yamauchi M, Yamaguchi T, Sugimoto T (2012) Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus. Osteoporos Int
36.
Zurück zum Zitat Hu X, Rui L, Zhu T, Xia H, Yang X, Wang X, Liu H, Lu Z, Jiang H (2011) Low testosterone level in middle-aged male patients with coronary artery disease. Eur J Intern Med 22:e133–136PubMedCrossRef Hu X, Rui L, Zhu T, Xia H, Yang X, Wang X, Liu H, Lu Z, Jiang H (2011) Low testosterone level in middle-aged male patients with coronary artery disease. Eur J Intern Med 22:e133–136PubMedCrossRef
37.
Zurück zum Zitat Svartberg J, von Muhlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland-Bugge E (2006) Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med 259:576–582PubMedCrossRef Svartberg J, von Muhlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland-Bugge E (2006) Low testosterone levels are associated with carotid atherosclerosis in men. J Intern Med 259:576–582PubMedCrossRef
Metadaten
Titel
Serum osteocalcin levels are inversely associated with abdominal aortic calcification in men with type 2 diabetes mellitus
verfasst von
N. Ogawa-Furuya
T. Yamaguchi
M. Yamamoto
I. Kanazawa
T. Sugimoto
Publikationsdatum
01.08.2013
Verlag
Springer London
Erschienen in
Osteoporosis International / Ausgabe 8/2013
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-013-2289-6

Weitere Artikel der Ausgabe 8/2013

Osteoporosis International 8/2013 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.