Skip to main content
Erschienen in: Osteoporosis International 1/2011

01.01.2011 | Original Article

Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus

verfasst von: I. Kanazawa, T. Yamaguchi, M. Yamauchi, M. Yamamoto, S. Kurioka, S. Yano, T. Sugimoto

Erschienen in: Osteoporosis International | Ausgabe 1/2011

Einloggen, um Zugang zu erhalten

Abstract

Summary

Although recent animal studies have shown that undercarboxylated osteocalcin acts as a hormone regulating glucose metabolism and fat mass, little is known about the relationships in humans. We reported here for the first time that undercarboxylated osteocalcin were associated with glucose/fat metabolism in patients with type 2 diabetes.

Introduction

Recent studies have shown that undercarboxylated osteocalcin (ucOC) acts as a hormone regulating glucose metabolism and fat mass. We investigated the relationship between ucOC as well as other bone turnover markers [serum OC, bone-specific alkaline phosphatase (BAP), and urinary N-terminal cross-linked telopeptide of type-I collagen] versus serum levels of glucose, fasting serum C-peptide, and adiponectin as well as the amount of fat mass in type 2 diabetes.

Methods

A total of 180 men and 109 postmenopausal women were consecutively recruited, and radiographic and biochemical characteristics were collected. Fat mass was measured by dual X-ray absorptiometry (DXA) and computed tomography (CT).

Results

In men, ucOC negatively correlated with percent trunk fat (%trunk fat; by DXA) and visceral/subcutaneous fat ratio (by CT) as well as fasting plasma glucose and HbA1c (at least p < 0.05). Multiple regression analysis showed that these associations were still significant independent of age, duration of diabetes, body stature, and renal function as well as glucose or fat metabolism, whereas BAP, another bone formation marker, did not correlate with any variable. On the other hand, although ucOC also negatively correlated with %fat and %trunk fat as well as HbA1c (at least p < 0.05) in postmenopausal women, we found no significant association in multiple regression analysis.

Conclusions

These findings suggest that ucOC is associated with plasma glucose level and fat mass in men with type 2 diabetes.
Literatur
1.
Zurück zum Zitat Lim S, Joung H, Shin CS, Lee HK, Kim KS, Shin EK, Kim HY, Lim MK, Cho SI (2004) Body composition changes with age have gender-specific impacts on bone mineral density. Bone 35:792–798CrossRefPubMed Lim S, Joung H, Shin CS, Lee HK, Kim KS, Shin EK, Kim HY, Lim MK, Cho SI (2004) Body composition changes with age have gender-specific impacts on bone mineral density. Bone 35:792–798CrossRefPubMed
2.
Zurück zum Zitat Felson DT, Zhang Y, Hannan MT, Anderson JJ (1993) Effects of weight and body mass index on bone mineral density in men and women. J Bone Miner Res 8:567–573CrossRefPubMed Felson DT, Zhang Y, Hannan MT, Anderson JJ (1993) Effects of weight and body mass index on bone mineral density in men and women. J Bone Miner Res 8:567–573CrossRefPubMed
3.
Zurück zum Zitat Glauber HS, Vollmer WM, Nevitt MC, Ensrud KE, Orwoll ES (1995) Body weight versus body fat distribution, adiposity, and frame size as predictors of bone density. J Clin Endocrinol Metab 80:1118–1123CrossRefPubMed Glauber HS, Vollmer WM, Nevitt MC, Ensrud KE, Orwoll ES (1995) Body weight versus body fat distribution, adiposity, and frame size as predictors of bone density. J Clin Endocrinol Metab 80:1118–1123CrossRefPubMed
4.
Zurück zum Zitat Maeda K, Okubo K, Shimomura I, Mizuno K, Matsuzawa Y, Matsubara K (1997) Analysis of an expression profile of genes in the human adipose tissue. Gene 190:227–235CrossRefPubMed Maeda K, Okubo K, Shimomura I, Mizuno K, Matsuzawa Y, Matsubara K (1997) Analysis of an expression profile of genes in the human adipose tissue. Gene 190:227–235CrossRefPubMed
5.
Zurück zum Zitat Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935CrossRefPubMed Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935CrossRefPubMed
6.
Zurück zum Zitat Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83CrossRefPubMed Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83CrossRefPubMed
7.
Zurück zum Zitat Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L (2001) Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 108:1875–1881PubMed Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L (2001) Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 108:1875–1881PubMed
8.
Zurück zum Zitat Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953CrossRefPubMed Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953CrossRefPubMed
9.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. BMC Cell Biol 8:51CrossRefPubMed Kanazawa I, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) Adiponectin and AMP kinase activator stimulate proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells. BMC Cell Biol 8:51CrossRefPubMed
10.
Zurück zum Zitat Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–849CrossRefPubMed Berner HS, Lyngstadaas SP, Spahr A, Monjo M, Thommesen L, Drevon CA, Syversen U, Reseland JE (2004) Adiponectin and its receptors are expressed in bone-forming cells. Bone 35:842–849CrossRefPubMed
11.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2009) Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus. Eur J Endocrinol 160:265–273CrossRefPubMed Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2009) Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus. Eur J Endocrinol 160:265–273CrossRefPubMed
12.
Zurück zum Zitat Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed
14.
Zurück zum Zitat Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRefPubMed Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRefPubMed
15.
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 USA 105:5266–5270CrossRefPubMed 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 105:5266–5270CrossRefPubMed
16.
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 94:45–49CrossRefPubMed 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 94:45–49CrossRefPubMed
17.
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 24:785–791CrossRefPubMed 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 24:785–791CrossRefPubMed
18.
Zurück zum Zitat Fernandez-Real JM, Izquierdo M, Ortega F, Gorostiaga E, Gomez-Ambrosi J, Moreno-Navarrete JM, Fruhbeck G, Martinez C, Idoate F, Salvador J, Forga L, Ricart W, Ibanez J (2009) The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 94:237–245CrossRefPubMed Fernandez-Real JM, Izquierdo M, Ortega F, Gorostiaga E, Gomez-Ambrosi J, Moreno-Navarrete JM, Fruhbeck G, Martinez C, Idoate F, Salvador J, Forga L, Ricart W, Ibanez J (2009) The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 94:237–245CrossRefPubMed
19.
Zurück zum Zitat Pitass AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832CrossRef Pitass AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832CrossRef
20.
Zurück zum Zitat Kaji H, Tobimatsu T, Naito J, Iu MF, Yamauchi M, Sugimoto T, Chihara K (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633CrossRefPubMed Kaji H, Tobimatsu T, Naito J, Iu MF, Yamauchi M, Sugimoto T, Chihara K (2006) Body composition and vertebral fracture risk in female patients treated with glucocorticoid. Osteoporos Int 17:627–633CrossRefPubMed
21.
Zurück zum Zitat Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K (1997) Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 12:1272–1279CrossRefPubMed Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K (1997) Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res 12:1272–1279CrossRefPubMed
22.
Zurück zum Zitat Kaji H, Nomura R, Yamauchi M, Chihara K, Sugimoto T (2006) The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism. Horm Metab Res 38:411–416CrossRefPubMed Kaji H, Nomura R, Yamauchi M, Chihara K, Sugimoto T (2006) The usefulness of bone metabolic indices for the prediction of changes in bone mineral density after parathyroidectomy in patients with primary hyperparathyroidism. Horm Metab Res 38:411–416CrossRefPubMed
23.
Zurück zum Zitat Nishimura J, Arai N, Tohmatsu J (2007) Measurement of serum undercarboxylated osteocalcin by ECLIA with the “Picolumi ucOC” kit. Clin Calcium 17:1702–1708 (in Japanese)PubMed Nishimura J, Arai N, Tohmatsu J (2007) Measurement of serum undercarboxylated osteocalcin by ECLIA with the “Picolumi ucOC” kit. Clin Calcium 17:1702–1708 (in Japanese)PubMed
24.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, 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 94:3031–3037CrossRefPubMed Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, 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 94:3031–3037CrossRefPubMed
25.
Zurück zum Zitat Lee NK, Karsenty G (2008) Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 19:161–166CrossRefPubMed Lee NK, Karsenty G (2008) Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 19:161–166CrossRefPubMed
26.
Zurück zum Zitat Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 124:573–582CrossRefPubMed Verhaeghe J, Suiker AM, Nyomba BL, Visser WJ, Einhorn TA, Dequeker J, Bouillon R (1989) Bone mineral homeostasis in spontaneously diabetic BB rats. II. Impaired bone turnover and decreased osteocalcin synthesis. Endocrinology 124:573–582CrossRefPubMed
27.
Zurück zum Zitat 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 16:1506–1512CrossRefPubMed 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 16:1506–1512CrossRefPubMed
28.
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 82:2915–2920CrossRefPubMed 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 82:2915–2920CrossRefPubMed
29.
Zurück zum Zitat Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res 39:871–875CrossRefPubMed Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T (2007) The combination of high glucose and advanced glycation end-products (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res 39:871–875CrossRefPubMed
30.
Zurück zum Zitat Rosato MT, Schneider SH, Shapses SA (1998) Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in noninsulin-dependent diabetes mellitus. Calcif Tissue Int 63:107–111CrossRefPubMed Rosato MT, Schneider SH, Shapses SA (1998) Bone turnover and insulin-like growth factor I levels increase after improved glycemic control in noninsulin-dependent diabetes mellitus. Calcif Tissue Int 63:107–111CrossRefPubMed
31.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2008) Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. Calcif Tissue Int 83:324–331CrossRefPubMed Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (2008) Combination of obesity with hyperglycemia is a risk factor for the presence of vertebral fractures in type 2 diabetic men. Calcif Tissue Int 83:324–331CrossRefPubMed
32.
Zurück zum Zitat Shea MK, Gundberg CM, Meiqs JB, Dallal GE, Saltzman E, Yoshida M, Jacques PF, Booth SL (2009) Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 90:1230–1235CrossRefPubMed Shea MK, Gundberg CM, Meiqs JB, Dallal GE, Saltzman E, Yoshida M, Jacques PF, Booth SL (2009) Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr 90:1230–1235CrossRefPubMed
33.
Zurück zum Zitat Gundberg CM, Nieman SD, Abrams S, Rosen H (1998) Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab 83:3258–3266CrossRefPubMed Gundberg CM, Nieman SD, Abrams S, Rosen H (1998) Vitamin K status and bone health: an analysis of methods for determination of undercarboxylated osteocalcin. J Clin Endocrinol Metab 83:3258–3266CrossRefPubMed
Metadaten
Titel
Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus
verfasst von
I. Kanazawa
T. Yamaguchi
M. Yamauchi
M. Yamamoto
S. Kurioka
S. Yano
T. Sugimoto
Publikationsdatum
01.01.2011
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 1/2011
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-010-1184-7

Weitere Artikel der Ausgabe 1/2011

Osteoporosis International 1/2011 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.