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Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy

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Abstract

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

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Abbreviations

BMI:

Body mass index

GCT:

Glucose challenge test

GDM:

Gestational diabetes mellitus

HOMA:

Homeostasis model assessment

IR:

Insulin resistance

OC:

Osteocalcin

OGTT:

Oral glucose tolerance test

QUICKI:

Quantitative insulin sensitivity check index

ucOC:

Undercarboxylated osteocalcin

References

  1. N.K. Lee, H. Sowa, E. Hinoi, M. Ferron, J.D. Ahn, C. Confavreux et al., Endocrine regulation of energy metabolism by the skeleton. Cell 130, 456–469 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. C.B. Confavreux, R.L. Levine, G. Karsenty, A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol. Cell. Endocrinol. 310, 21–29 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. M. Ferron, J. Wei, T. Yoshizawa, A. Del Fattore, R.A. DePinho, A. Teti et al., Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142, 296–308 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. S.L. Booth, A. Centi, S.R. Smith, C. Gundberg, The role of osteocalcin in human glucose metabolism: marker or mediator? Nat. Rev. Endocrinol. 9, 43–55 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. Y. Bao, M. Zhou, Z. Lu, H. Li, Y. Wang, L. Sun et al., Serum levels of osteocalcin are inversely associated with the metabolic syndrome and the severity of coronary artery disease in Chinese men. Clin. Endocrinol. 75, 196–201 (2011)

    Article  CAS  Google Scholar 

  6. J.M. Kindblom, C. Ohlsson, O. Ljunggren, M.K. Karlsson, A. Tivesten, U. Smith et al., Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J. Bone Miner. Res. 24, 785–791 (2009)

    Article  CAS  PubMed  Google Scholar 

  7. M.K. Shea, C.M. Gundberg, J.B. Meigs, G.E. Dallal, E. Saltzman, M. Yoshida et al., Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am. J. Clin. Nutr. 90, 1230–1235 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. A.G. Pittas, S.S. Harris, M. Eliades, P. Stark, B. Dawson-Hughes, Association between serum osteocalcin and markers of metabolic phenotype. J. Clin. Endocrinol. Metab. 94, 827–832 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. Y.C. Hwang, I.K. Jeong, K.J. Ahn, H.Y. Chung, 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 (2009)

    Article  CAS  PubMed  Google Scholar 

  10. K. Miehle, H. Stepan, M. Fasshauer, Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin. Endocrinol. (Oxf). 76(1), 2–11 (2012)

    Article  CAS  PubMed  Google Scholar 

  11. M. Lacroix, M.C. Battista, M. Doyon, J. Ménard, J.L. Ardilouze, P. Perron, M.F. Hivert, Lower adiponectin levels at first trimester of pregnancy are associated with increased insulin resistance and higher risk of developing gestational diabetes mellitus. Diabetes Care 36(6), 1577–1583 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Y. Winhofer, A. Handisurya, A. Tura, C. Bittighofer, K. Klein, B. Schneider et al., Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 33, 139–143 (2010)

    Article  CAS  PubMed  Google Scholar 

  13. N. Tabatabaei, Y. Giguère, J.C. Forest, C.J. Rodd, R. Kremer, H.A. Weiler, Osteocalcin is higher across pregnancy in Caucasian women with gestational diabetes mellitus. Can. J. Diabetes 38, 307–313 (2014)

    Article  PubMed  Google Scholar 

  14. W. Khovidhunkit, P. Pruksakorn, W. Plengpanich, T. Tharavanij, Retinol-binding protein 4 is not associated with insulin resistance in pregnancy. Metabolism 61, 65–69 (2012)

    Article  CAS  PubMed  Google Scholar 

  15. B.E. Metzger, D.R. Coustan, Summary and recommendations of the fourth international workshop-conference on gestational diabetes mellitus. The Organizing Committee. Diabetes Care 21(Suppl 2), B161–B167 (1998)

    PubMed  Google Scholar 

  16. A.L. Schafer, D.E. Sellmeyer, A.V. Schwartz, C.J. Rosen, E. Vittinghoff, L. Palermo, J.P. Bilezikian, D.M. Shoback, D.M. Black, Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J. Clin. Endocrinol. Metab. 96(12), E1982–E1989 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. A.B. Choudhury, P.D. Sarkar, D.K. Sakalley, S.B. Petkar, Role of adiponectin in mediating the association of osteocalcin with insulin resistance and type 2 diabetes: a cross sectional study in pre- and post-menopausal women. Arch. Physiol. Biochem. 120(2), 73–79 (2014)

    Article  CAS  PubMed  Google Scholar 

  18. C. Boucher-Berry, P.W. Speiser, D.E. Carey, S.P. Shelov, S. Accacha, I. Fennoy, R. Rapaport, Y. Espinal, M. Rosenbaum, Vitamin D, osteocalcin and risk for adiposity as co-morbidities in middle school children. J. Bone Miner. Res. 27(2), 283–293 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. G.S. Caglar, E.D. Ozdemir, M. Kiseli, S. Demirtas, S.D. Cengiz, The association of osteocalcin and adiponectin with glucose metabolism in nondiabetic postmenopausal women. Gynecol. Obstet. Invest. 77(4), 255–260 (2014)

    Article  CAS  PubMed  Google Scholar 

  20. R. Saucedo, G. Rico, G. Vega, L. Basurto, L. Cordova, R. Galvan, M. Hernandez, E. Puello, A. Zarate, Osteocalcin, under-carboxylated osteocalcin and osteopontin are not associated with gestational diabetes mellitus but are inversely associated with leptin in non-diabetic women. J. Endocrinol. Invest. 38, 519–526 (2015)

    Article  CAS  PubMed  Google Scholar 

  21. B. Telejko, K. Kalejta, M. Kuzmicki, N. Wawrusiewicz-Kurylonek, D. Lipinska, J. Pliszka, J. Wilk, A. Zielinska, A. Sobota, J. Szamatowicz, A. Kretowski, M. Gorska, The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes. Ann. Agric. Environ. Med. 22(2), 307–312 (2015)

    Article  PubMed  Google Scholar 

  22. U. Ulrich, P.B. Miller, D.R. Eyre, C.H. Chesnut III, H. Schlebusch, M.R. Soules, Bone remodeling and bone mineral density during pregnancy. Arch. Gynecol. Obstet. 268, 309–316 (2003)

    Article  CAS  PubMed  Google Scholar 

  23. D.E. Cole, C.M. Gundberg, L.J. Stirk, S.A. Atkinson, D.A. Hanley, L.M. Ayer, L.S. Baldwin, Changing osteocalcin concentrations during pregnancy and lactation: implications for maternal mineral metabolism. J. Clin. Endocrinol. Metab. 65, 290–294 (1987)

    Article  CAS  PubMed  Google Scholar 

  24. A. Akesson, M. Vahter, M. Berglund, T. Eklöf, K. Bremme, P. Bjellerup, Bone turnover from early pregnancy to postweaning. Acta Obstet. Gynecol. Scand. 83, 1049–1055 (2004)

    Article  PubMed  Google Scholar 

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Acknowledgments

This study received funding support from the Ratchadapiseksompotch Fund (RA56/022) and the Thailand Government Research Budget (011/2549), who had no role in the design, conduct, or report. We are grateful to Dr. Promphan Pruksakorn for help with the study.

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Authors and Affiliations

  1. Hormonal and Metabolic Disorders Research Unit and Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Samakkee Payabarn Bldg., 2nd floor, King Chulalongkorn Memorial Hospital, Rama IV Road, Patumwan, Bangkok, 10330, Thailand

    Panudda Srichomkwun, Natnicha Houngngam, Lalita Wattanachanya & Weerapan Khovidhunkit

  2. Department of Medicine, and Excellence Center for Diabetes, Hormone, and Metabolism, King Chulalongkorn Memorial Hospital, Bangkok, Thailand

    Panudda Srichomkwun, Natnicha Houngngam, Sophitsachi Pasatrat, Lalita Wattanachanya & Weerapan Khovidhunkit

  3. Department of Medicine, Faculty of Medicine, Thammasat University, Pathumthani, Thailand

    Thipaporn Tharavanij

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  1. Panudda Srichomkwun
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  2. Natnicha Houngngam
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  3. Sophitsachi Pasatrat
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  4. Thipaporn Tharavanij
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  5. Lalita Wattanachanya
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  6. Weerapan Khovidhunkit
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Correspondence to Lalita Wattanachanya or Weerapan Khovidhunkit.

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Srichomkwun, P., Houngngam, N., Pasatrat, S. et al. Undercarboxylated osteocalcin is associated with insulin resistance, but not adiponectin, during pregnancy. Endocrine 53, 129–135 (2016). https://doi.org/10.1007/s12020-015-0829-x

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  • DOI: https://doi.org/10.1007/s12020-015-0829-x

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