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Journal of Endocrinological Investigation
Published in: Journal of Endocrinological Investigation 5/2015

01-05-2015 | Original Article

Osteocalcin, under-carboxylated osteocalcin and osteopontin are not associated with gestational diabetes mellitus but are inversely associated with leptin in non-diabetic women

Authors: R. Saucedo, G. Rico, G. Vega, L. Basurto, L. Cordova, R. Galvan, M. Hernandez, E. Puello, A. Zarate

Published in: Journal of Endocrinological Investigation | Issue 5/2015

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Abstract

Objective

To measure serum osteocalcin (OC), under-carboxylated osteocalcin (ucOC), osteopontin (OPN), and leptin in pregnant women with gestational diabetes mellitus (GDM) and in healthy pregnant women during pregnancy and after birth and relate these markers to glucose metabolism.

Methods

This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Serum OC, ucOC, OPN, leptin, insulin and insulin resistance were evaluated during the study.

Results

Bone biomarkers and leptin were similar between GDM and normal pregnancy. After delivery, OC, ucOC and OPN increased in both groups, while leptin decreased only in healthy controls. Bone markers did not correlate with insulin and insulin resistance in the two groups, but leptin was positively correlated with insulin and insulin resistance and negatively correlated with bone biomarkers only in healthy women. Furthermore, the women who developed diabetes postpartum had lower levels of OC than women with normal glucose tolerance.

Conclusion

GDM is not associated with OC, ucOC, OPN, and leptin and does not correlate with insulin resistance. At postpartum, women who develop diabetes have lower osteocalcin concentrations. Leptin correlates with insulin resistance and bone biomarkers in non-diabetic women.
Literature
1.
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 130:456–469CrossRefPubMedCentralPubMed
2.
Aarden EM, Wassenaar AM, Alblas MJ, Nijweide PJ (1996) Immunocytochemical demonstration of extracellular matrix proteins in isolated osteocytes. Histochem Cell Biol 106:495–501CrossRefPubMed
3.
Delmas PD (1992) Clinical use of biochemical markers of bone remodeling in osteoporosis. Bone 13(Suppl 1):S17–S21CrossRefPubMed
4.
5.
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 105:5266–5270CrossRefPubMedCentralPubMed
6.
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 94:827–832CrossRefPubMedCentralPubMed
7.
Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellström D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791CrossRefPubMed
8.
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
9.
Kiefer FW, Zeyda M, Gollinger K, Pfau B, Neuhofer A, Weichhart T, Säemann MD, Geyeregger R, Schlederer M, Kenner L, Stulnig TM (2010) Neutralization of osteopontin inhibits obesity-induced inflammation and insulin resistance. Diabetes 59:935–946CrossRefPubMedCentralPubMed
10.
Scatena M, Liaw L, Giachelli CM (2007) Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 27:2302–2309CrossRefPubMed
11.
Yamaguchi H, Igarashi M, Hirata A, Tsuchiya H, Sugiyama K, Morita Y, Jimbu Y, Ohnuma H, Daimon M, Tominaga M, Kato T (2004) Progression of diabetic nephropathy enhances the plasma osteopontin level in type 2 diabetic patients. Endocr J 51:499–504CrossRefPubMed
12.
Gravenstein KS, Napora JK, Short RG, Ramachandran R, Carlson OD, Metter EJ, Ferrucci L, Egan JM, Chia CW (2011) Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J Clin Endocrinol Metab 96:E884–E890CrossRefPubMedCentralPubMed
13.
Karsenty G (2006) Convergence between bone and energy homeostases: leptin regulation of bone mass. Cell Metab 4:341–348CrossRefPubMed
14.
Confavreux CB (2011) Bone: from a reservoir of minerals to a regulator of energy metabolism. Kidney Int Suppl 1:S14–S19CrossRef
15.
American Diabetes Association (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37(Suppl 1):S81–S90CrossRef
16.
Capula C, Mazza T, Vero R, Constane G (2013) HbA1-c levels in patients with gestational diabetes mellitus: relationship with pre-pregnancy BMI and pregnancy outcome. J Endocrinol Invest 36:1038–1045PubMed
17.
Kim C, Newton KM, Knopp RH (2002) Gestational diabetes and the incidence of type 2 diabetes: a systematic review. Diabetes Care 25:1862–1878CrossRefPubMed
18.
Bellamy L, Casas JP, Hingorani AD, Williams D (2009) Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet 373:1773–1779CrossRefPubMed
19.
Winhofer Y, Handisurya A, Tura A, Bittighofer C, Klein K, Schneider B, Bieglmayer C, Wagner OF, Pacini G, Luger A, Kautzky-Willer A (2010) Osteocalcin is related to enhanced insulin secretion in gestational diabetes mellitus. Diabetes Care 33:139–143CrossRefPubMedCentralPubMed
20.
Winhofer Y, Kiefer FW, Handisurya A, Tura A, Klein K, Schneider B, Marculescu R, Wagner OF, Pacini G, Luger A, Stulnig TM, Kautzky-Willer A (2012) CTX (crosslaps) rather than osteopontin is associated with disturbed glucose metabolism in gestational diabetes. PLoS One 7:e40947CrossRefPubMedCentralPubMed
21.
Tabatabaei N, Giguère Y, Forest JC, Rodd CJ, Kremer R, Weiler HA (2014) Osteocalcin is higher across pregnancy in Caucasian women with gestational diabetes mellitus. Can J Diabetes 38:307–313CrossRefPubMed
22.
Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P (2003) International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395CrossRefPubMed
23.
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 28:412–419CrossRefPubMed
24.
Cole DE, Gundberg CM, Stirk LJ, Atkinson SA, Hanley DA, Ayer LM, Baldwin LS (1987) Changing osteocalcin concentrations during pregnancy and lactation: implications for maternal mineral metabolism. J Clin Endocrinol Metab 65:290–294CrossRefPubMed
25.
Henderson PH, Sowers M, Kutzko KE, Jannausch ML (2000) Bone mineral density in grand multiparous women with extended lactation. Am J Obstet Gynecol 182:1371–1377CrossRefPubMed
26.
Tsvetov G, Levy S, Benbassat C, Shraga-Slutzky I, Hirsch D (2014) Influence of number of deliveries and total breast-feeding time on bone mineral density in premenopausal and young postmenopausal women. Maturitas 77:249–254CrossRefPubMed
27.
Viljakainen H, Ivaska KK, Paldánius P, Lipsanen-Nyman M, Saukkonen T, Pietiläinen KH, Andersson S, Laitinen K, Mäkitie O (2014) Suppressed bone turnover in obesity: a link to energy metabolism? A case–control study. J Clin Endocrinol Metab 99:2155–2163CrossRefPubMed
28.
Cohen A, Dempster DW, Recker RR, Lappe JM, Zhou H, Zwahlen A, Müller R, Zhao B, Guo X, Lang T, Saeed I, Liu XS, Guo XE, Cremers S, Rosen CJ, Stein EM, Nickolas TL, McMahon DJ, Young P, Shane E (2013) Abdominal fat is associated with lower bone formation and inferior bone quality in healthy premenopausal women: a transiliac bone biopsy study. J Clin Endocrinol Metab 98:2562–2572CrossRefPubMedCentralPubMed
29.
Lester ME, Urso ML, Evans RK, Pierce JR, Spiering BA, Maresh CM, Hatfield DL, Kraemer WJ, Nindl BC (2009) Influence of exercise mode and osteogenic index on bone biomarker responses during short-term physical training. Bone 45:768–769CrossRefPubMed
30.
Sinha N, Shieh A, Stein EM, Strain G, Schulman A, Pomp A, Gagner M, Dakin G, Christos P, Bockman RS (2011) Increased PTH and 1.25(OH)(2)D levels associated with increased markers of bone turnover following bariatric surgery. Obesity 19:2388–2393CrossRefPubMedCentralPubMed
31.
Pi M, Wu Y, Quarles LD (2011) GPRC6A mediates responses to osteocalcin in beta-cells in vitro and pancreas in vivo. J Bone Miner Res 26:1680–1683CrossRefPubMed
32.
Mizokami A, Yasutake Y, Gao J, Matsuda M, Takahashi I, Takeuchi H (2013) Osteocalcin induces release of glucagon-like peptide-1 and thereby stimulates insulin secretion in mice. PLoS One 8:e57375CrossRefPubMedCentralPubMed
33.
Ferron M, McKee MD, Levine RL, Karsenty G, Ducy P (2012) Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50:568–575CrossRefPubMedCentralPubMed
34.
35.
Zeyda M, Gollinger K, Todoric J, Kiefer FW, Keck M, Aszmann O, Prager G, Zlabinger GJ, Petzelbauer P, Stulnig TM (2011) Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function. Endocrinology 152:2219–2227CrossRefPubMed
36.
Ducy P (2011) The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 54:1291–1297CrossRefPubMed
37.
Barbour LA, McCurdy CE, Hernandez TL, Kirwan JP, Catalano PM, Friedman JE (2007) Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes. Diabetes Care 30(Suppl 2):S112–S119CrossRefPubMed
38.
Miehle K, Stepan H, Fasshauer M (2012) Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol 76:2–11CrossRef
39.
Boyadzhieva M, Atanasova I, Zacharieva S, Kedikova S (2013) Adipocytokines during pregnancy and postpartum in women with gestational diabetes and healthy controls. J Endocrinol Invest 36:944–949PubMed
40.
Kautzky-Willer A, Pacini G, Tura A, Bieglmayer C, Schneider B, Ludvik B, Prager R, Waldhäusl W (2001) Increased plasma leptin in gestational diabetes. Diabetologia 44:164–172CrossRefPubMed
41.
Chen D, Xia G, Xu P, Dong M (2010) Peripartum serum leptin and soluble leptin receptor levels in women with gestational diabetes. Acta Obstet Gynecol Scand 89:1595–1599CrossRefPubMed
42.
Saucedo R, Zarate A, Basurto L, Hernández M, Puello E, Galvan R, Campos S (2011) Relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes. Arch Med Res 42:318–323CrossRefPubMed
43.
Saad MF, Khan A, Sharma A, Michael R, Riad-Gabriel MG, Boyadjian R, Jinagouda SD, Steil GM, Kamdar V (1998) Physiological insulinemia acutely modulates plasma leptin. Diabetes 47:544–549CrossRefPubMed
44.
Utriainen T, Malmstroem R, Maekimattila S, Yki-Järvinen H (1996) Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects. Diabetes 45:1364–1366CrossRefPubMed
45.
Zeigerer A, Rodeheffer MS, McGraw TE, Friedman JM (2008) Insulin regulates leptin secretion from 3T3eL1 adipocytes by a PI 3 kinase independent mechanism. Exp Cell Res 314:2249–2256CrossRefPubMedCentralPubMed
46.
Kieffer TJ, Habener JF (2000) The adipoinsular axis: effects of leptin on pancreatic beta-cells. Am J Physiol Endocrinol Metab 278:E1–E14PubMed
47.
Ducy P, Takeda S, Amling M, Schilling AF, Priemel M, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207CrossRefPubMed
48.
Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C, Karsenty G (2005) Leptin regulation of bone resorption by the sympathetic nervous system and CART. Nature 434:514–520CrossRefPubMed
49.
Lu C, Ivaska KK, Alen M, Wang Q, Törmäkangas T, Xu L, Wiklund P, Mikkola TM, Pekkala S, Tian H, Väänänen HK, Cheng S (2012) Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women. J Clin Endocrinol Metab 97:4106–4114CrossRefPubMed
50.
Tamura T, Yoneda M, Yamane K, Nakanishi S, Nakashima R, Okubo M, Kohno N (2007) Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus. Metabolism 56:623–628CrossRefPubMed
51.
52.
Ulrich U, Miller PB, Eyre DR, Chesnut CH, Schlebusch H, Soules MR (2003) Bone remodeling and bone mineral density during pregnancy. Arch Gynecol Obstet 268:309–316CrossRefPubMed
53.
Sowers M, Scholl T, Grewal J, Chen X, Jannausch M (2001) IGF-I, osteocalcin, and bone change in pregnant normotensive and pre-eclamptic women. J Clin Endocrinol Metab 86:5898–5903CrossRefPubMed
54.
Naylor KE, Iqbal P, Fledelius C, Fraser RB, Eastell R (2000) The effect of pregnancy on bone density and bone turnover. J Bone Miner Res 15:129–137CrossRefPubMed
55.
Aberg AE, Jönsson EK, Eskilsson I, Landin-Olsson M, Frid AH (2002) Predictive factors of developing diabetes mellitus in women with gestational diabetes. Acta Obstet Gynecol Scand 81:11–16CrossRefPubMed
56.
Metzger BE, Bybee DE, Freinkel N, Phelps RL, Radvany RM, Vaisrub N (1985) Gestational diabetes mellitus. Correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during the first year postpartum. Diabetes 34(Suppl 2):111–115CrossRefPubMed
57.
Retnakaran R, Qi Y, Sermer M, Connelly PW, Hanley AJ, Zinman B (2008) Glucose intolerance in pregnancy and future risk of pre-diabetes or diabetes. Diabetes Care 31:2026–2031CrossRefPubMedCentralPubMed
58.
Notsu M, Yamaguchi T, Okazaki K, Tanaka K, Ogawa N, Kanazawa I, Sugimoto T (2014) Advanced glycation end product 3 (AGE3) suppresses the mineralization of mouse stromal ST2 cells and human mesenchymal stem cells by increasing TGF-β expression and secretion. Endocrinology 155:2402–2410CrossRefPubMed
59.
Freude T, Braun KF, Haug A, Pscherer S, Stöckle U, Nussler AK, Ehnert S (2012) Hyperinsulinemia reduces osteoblast activity in vitro via upregulation of TGF-β. J Mol Med 90:1257–1266CrossRefPubMed
60.
Sayinalp S, Gedik O, Koray Z (1995) Increasing serum osteocalcin after glycemic control in diabetic men. Calcif Tissue Int 57:422–425CrossRefPubMed
61.
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
62.
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 94:3031–3037CrossRefPubMed
63.
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 142:296–308CrossRefPubMedCentralPubMed
Metadata
Title
Osteocalcin, under-carboxylated osteocalcin and osteopontin are not associated with gestational diabetes mellitus but are inversely associated with leptin in non-diabetic women
Authors
R. Saucedo
G. Rico
G. Vega
L. Basurto
L. Cordova
R. Galvan
M. Hernandez
E. Puello
A. Zarate
Publication date
01-05-2015
Publisher
Springer International Publishing
Published in
Journal of Endocrinological Investigation / Issue 5/2015
Electronic ISSN: 1720-8386
DOI
https://doi.org/10.1007/s40618-014-0220-4

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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.

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