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Erschienen in: Osteoporosis International 3/2013

01.03.2013 | Short Communication

Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus

verfasst von: I. Kanazawa, K. Tanaka, N. Ogawa, M. Yamauchi, T. Yamaguchi, T. Sugimoto

Erschienen in: Osteoporosis International | Ausgabe 3/2013

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Abstract

Summary

Although a recent study showed that undercarboxylated osteocalcin (ucOC) is important for male fertility and testosterone production by testes, little is known about the relationship between ucOC and testosterone in humans. We found for the first time that ucOC is positively associated with free testosterone in men with type 2 diabetes.

Introduction

The ucOC has been shown to play a key role in energy metabolism as an endocrine hormone. Although a recent animal study demonstrated that ucOC is also important for male fertility and testosterone production by the testes, association between serum osteocalcin and testosterone levels has not been understood in humans.

Methods

Sixty-nine male patients with type 2 diabetes were recruited and chemical bone markers [total osteocalcin (TOC), ucOC, bone-specific alkaline phosphatase (BAP), and urinary N-terminal cross-linked telopeptide of type I collagen (uNTX)], gonadotropic hormones [luteinizing hormone (LH) and follicle-stimulating hormone (FSH)], and free testosterone (FT) were measured.

Results

Multiple regression analysis showed that ucOC and ucOC/TOC ratio were associated positively with FT and negatively with LH (for ucOC, β = 0.30, p = 0.042 and β = −0.52, p = 0.048; for ucOC/TOC ratio, β = 0.31, p = 0.031 and β = −0.54, p = 0.036, respectively) independently of age, duration of diabetes, body mass index, and hemoglobin A1c. ucOC and ucOC/TOC ratio were significantly associated with FT even after adjusting for LH and FSH (β = 0.24, p = 0.042 and β = 0.25, p = 0.031, respectively). However, neither TOC, BAP, nor uNTX was associated with the gonadotropic hormones or FT levels.

Conclusions

The present study indicates for the first time that ucOC is associated positively with FT and negatively with LH in type 2 diabetes. These findings support the recent evidence that ucOC is involved in testosterone production in male subjects.
Literatur
1.
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 130:456–469PubMedCrossRef 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 130:456–469PubMedCrossRef
2.
Zurück zum Zitat Fulzele K, Riddle RC, Digirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Bruning JC, Clemens TL (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319PubMedCrossRef Fulzele K, Riddle RC, Digirolamo DJ, Cao X, Wan C, Chen D, Faugere MC, Aja S, Hussain MA, Bruning JC, Clemens TL (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319PubMedCrossRef
3.
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
4.
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
5.
Zurück zum Zitat Kanazawa I, Yamaguchi T, Tada Y, Yamauchi M, Yano S, Sugimoto T (2011) Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 48:270–275CrossRef Kanazawa I, Yamaguchi T, Tada Y, Yamauchi M, Yano S, Sugimoto T (2011) Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 48:270–275CrossRef
6.
Zurück zum Zitat Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809PubMedCrossRef Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith CE, Hermo L, Suarez S, Roth BL, Ducy P, Karsenty G (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809PubMedCrossRef
7.
Zurück zum Zitat Pi M, Wu Y, Quarles LD (2011) GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo. J Miner Bone Res 26:1680–1683CrossRef Pi M, Wu Y, Quarles LD (2011) GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo. J Miner Bone Res 26:1680–1683CrossRef
8.
Zurück zum Zitat Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M (2011) Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 34:528–540PubMedCrossRef Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M (2011) Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 34:528–540PubMedCrossRef
9.
Zurück zum Zitat Lindau ST, Tang H, Gomero A, Vable A, Huang ES, Drum ML, Qato DM, Chin MH (2010) Sexuality among middle-aged and older adults with diagnosed and undiagnosed diabetes: a national, population-based study. Diabetes Care 33:2202–2210PubMedCrossRef Lindau ST, Tang H, Gomero A, Vable A, Huang ES, Drum ML, Qato DM, Chin MH (2010) Sexuality among middle-aged and older adults with diagnosed and undiagnosed diabetes: a national, population-based study. Diabetes Care 33:2202–2210PubMedCrossRef
10.
Zurück zum Zitat Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523PubMedCrossRef Saito M, Fujii K, Mori Y, Marumo K (2006) Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 17:1514–1523PubMedCrossRef
11.
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 94:3031–3037PubMedCrossRef 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 94:3031–3037PubMedCrossRef
12.
Zurück zum Zitat Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, Hanafusa T, Haneda M, Ueki K, The Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus (2010) Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetol Int 1:2–20CrossRef Seino Y, Nanjo K, Tajima N, Kadowaki T, Kashiwagi A, Araki E, Ito C, Inagaki N, Iwamoto Y, Kasuga M, Hanafusa T, Haneda M, Ueki K, The Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus (2010) Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetol Int 1:2–20CrossRef
13.
Zurück zum Zitat Kirmani S, Atkinson EJ, Melton LJ 3rd, Riggs BL, Amin S, Khosla S (2011) Relationship of testosterone and osteocalcin levels during growth. J Bone Miner Res 26:2212–2216PubMedCrossRef Kirmani S, Atkinson EJ, Melton LJ 3rd, Riggs BL, Amin S, Khosla S (2011) Relationship of testosterone and osteocalcin levels during growth. J Bone Miner Res 26:2212–2216PubMedCrossRef
14.
Zurück zum Zitat Avasthi A, Grover S, Bhansali A, Dash RJ, Gupta N, Sharan P, Sharma S (2011) Erectile dysfunction in diabetes mellitus contributes to poor quality of life. Int Rev Phychiatry 23:93–99CrossRef Avasthi A, Grover S, Bhansali A, Dash RJ, Gupta N, Sharan P, Sharma S (2011) Erectile dysfunction in diabetes mellitus contributes to poor quality of life. Int Rev Phychiatry 23:93–99CrossRef
15.
Zurück zum Zitat Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef Vestergaard P (2007) Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes—a meta-analysis. Osteoporos Int 18:427–444PubMedCrossRef
16.
Zurück zum Zitat Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of bone mineral density or diabetic complications. J Bone Miner Res 24:702–709PubMedCrossRef Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T (2009) Diabetic patients have an increased risk of vertebral fractures independent of bone mineral density or diabetic complications. J Bone Miner Res 24:702–709PubMedCrossRef
17.
Zurück zum Zitat Botolin S, MacCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424PubMedCrossRef Botolin S, MacCabe LR (2006) Chronic hyperglycemia modulates osteoblast gene expression through osmotic and non-osmotic pathways. J Cell Biochem 99:411–424PubMedCrossRef
18.
Zurück zum Zitat Torrens JI, Skurnick J, Davidow AL, Korenman SG, Santoro N, Soto-Greene M, Lasser N, Weiss G, Study of Women’s Health Across the Nation (SWAN) (2004) Ethnic differences in insulin sensitivity and beta-cell function in premenopausal or early perimenopausal women without diabetes: the Study of Women's Health Across the Nation (SWAN). Diabetes Care 27:354–361PubMedCrossRef Torrens JI, Skurnick J, Davidow AL, Korenman SG, Santoro N, Soto-Greene M, Lasser N, Weiss G, Study of Women’s Health Across the Nation (SWAN) (2004) Ethnic differences in insulin sensitivity and beta-cell function in premenopausal or early perimenopausal women without diabetes: the Study of Women's Health Across the Nation (SWAN). Diabetes Care 27:354–361PubMedCrossRef
Metadaten
Titel
Undercarboxylated osteocalcin is positively associated with free testosterone in male patients with type 2 diabetes mellitus
verfasst von
I. Kanazawa
K. Tanaka
N. Ogawa
M. Yamauchi
T. Yamaguchi
T. Sugimoto
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Osteoporosis International / Ausgabe 3/2013
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-012-2017-7

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