РОЛЬ МАРКЕРА КОСТНОГО РЕМОДЕЛИРОВАНИЯ ОСТЕОКАЛЬЦИНА В РЕГУЛЯЦИИ ЭНЕРГЕТИЧЕСКОГО ГОМЕОСТАЗА ПРИ САХАРНОМ ДИАБЕТЕ 2 ТИПА

  • Ковальчук А. В. к. мед. н., ГУ «Институт эндокринологии и обмена веществ им. В. П. Комиссаренко НАМН Украины», г. Киев, Украина https://orcid.org/0000-0001-6591-1460
  • Зиныч О. В. д. мед.н., ГУ «Институт эндокринологии и обмена веществ им. В. П. Комиссаренко НАМН Украины», г. Киев, Украина https://orcid.org/0000-0002-0516-0148
  • Корпачев В. В. д. мед. н., ГУ «Институт эндокринологии и обмена веществ им. В. П. Комиссаренко НАМН Украины», г. Киев, Украина https://orcid.org/0000-0003-0182-9753
  • Кушнарева Н. Н. к. мед. н., ГУ «Институт эндокринологии и обмена веществ им. В. П. Комиссаренко НАМН Украины», г. Киев, Украина https://orcid.org/0000-0002-5390-6784
  • Прибила О. В. ГУ «Институт эндокринологии и обмена веществ им. В. П. Комиссаренко НАМН Украины», г. Киев, Украина https://orcid.org/0000-0003-2212-1172
Keywords: diabetes mellitus type 2, osteocalcin, index of visceral obesity, bone mineral density, insulin resistance

Abstract

Osteocalcin (OK) is actively involved in the humoral regulation of energy homeostasis. However, the relationship between the level of OK as a modulator of metabolic processes and constitutional and metabolic features in patients with type 2 diabetes mellitus (DM) of a different gender remains not thoroughly studied.
The study included 127 patients with type 2 diabetes ≥ 50 years of age. Of these, 70 were postmenopausal women and 57 men.
It was found that in the general group of women, the concentration of OK in the blood serum was significantly higher than in men. The observed difference is due to significantly higher levels of OK in women of the older age group (≥ 60 years) in comparison with men. At the same time, a decrease in bone mineral density (BMD) in the femoral neck was observed in subgroups of men and women aged ≥ 60 years and older, while in the younger subgroups of patients, the BMD of lumbar and femoral zones were close to each other.
The relationships between OK levels and adipose tissue parameters, evaluated by calculating the morphological and functional index of visceral obesity (IVO), were investigated. An increase in the OK level in the groups of men and women was accompanied by a decrease in the IVO values. The highest degree of insulin resistance was determined in groups of patients with minimal levels of OK and high IVO, and the lowest values were recorded in patients with high levels of OK and low IVO.
The decrease of the blood OK level in patients with type 2 diabetes occurs in parallel with an increase in the degree of insulin resistance and dysfunction of visceral adipose tissue. In this case, IVO is a more accurate parameter reflecting the constitutional and metabolic phenotypic changes, compared with the index of the waist circumference. The decrease in BMD in patients with type 2 diabetes is the result of predominantly involutive processes that are noticeable at the age of ≥ 60 years and occur against the background of a decrease in the content of OK with age.

References

Amato, M. C., Giordano, C., Galia, M., Criscimanna, A., Vitabile, S., Midiri, M., Galluzzo, A., & AlkaMeSy Study Group (2010). Visceral Adiposity Index: a reliable indicator of visceral fat function associated with cardiometabolic risk. Diabetes care, 33(4), 920–922. https://doi.org/10.2337/dc09-1825

American Diabetes Association Releases 2018 Standards of Medical Care in Diabetes, with Notable New Recommendations for People with Cardiovascular Disease and Diabetes. Arlington, Virginia, December 8, 2017. Retrieved from https://diabetes.org

Arrieta, F., Iglesias, A. F. P., Piñera, M., Quiñones A. A. J., et al. (2017) Serum Concentrations of Osteocalcin (OC) and Beta-Cross Laps (Beta-CTx) and Insulin Resistance in Morbid Obese Women with and without DM2. Glob J Obes Diabetes Metab Syndr. 4(3), 072–076.

Bilić-Ćurčić, I., Makarović, S., Mihaljević, I., Franceschi, M., & Jukić, T. (2017). Bone Mineral Density in Relation to Metabolic Syndrome Components in Postmenopausal Women with Diabetes Mellitus Type 2. Acta clinica Croatica, 56(1), 58–63. https://doi.org/10.20471/acc.2017.56.01.09

Brennan-Speranza, T. C., & Conigrave, A. D. (2015). Osteocalcin: an osteoblast-derived polypeptide hormone that modulates whole body energy metabolism. Calcified tissue international, 96(1), 1–10. https://doi.org/10.1007/s00223-014-9931-y

Chen, L., Li, Q., Yang, Z., Ye, Z., Huang, Y., He, M., Wen, J., Wang, X., Lu, B., Hu, J., Liu, C., Ling, C., Qu, S., & Hu, R. (2013). Osteocalcin, glucose metabolism, lipid profile and chronic low-grade inflammation in middle-aged and elderly Chinese. Diabetic medicine: a journal of the British Diabetic Association, 30(3), 309–317. https://doi.org/10.1111/j.1464-5491.2012.03769.x

Chen, S. M., Peng, Y. J., Wang, C. C., Su, S. L., Salter, D. M., & Lee, H. S. (2018). Dexamethasone Downregulates Osteocalcin in Bone Cells through Leptin Pathway. International journal of medical sciences, 15(5), 507–516. https://doi.org/10.7150/ijms.21881

Chodankar, R., Wu, D. Y., Schiller, B. J., Yamamoto, K. R., & Stallcup, M. R. (2014). Hic-5 is a transcription coregulator that acts before and/or after glucocorticoid receptor genome occupancy in a geneselective manner. Proceedings of the National Academy of Sciences of the United States of America, 111(11), 4007–4012. https://doi.org/10.1073/pnas.1400522111

Clemens, T. L., & Karsenty, G. (2011). The osteoblast: an insulin target cell controlling glucose homeostasis. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research, 26(4), 677–680. https://doi.org/10.1002/jbmr.321

Eliseev, R., White, N. (2016). Cross-talk between oxidative metabolism and osteogenic signaling. ASBMR Annual Meeting September 2016, Atlanta, Georgia, USA. PS Number SA0072

Fernandes, T., Gonçalves, L., & Brito, J. (2017). Relationships between Bone Turnover and Energy Metabolism. Journal of diabetes research, 2017, 9021314. https://doi.org/10.1155/2017/9021314

Fernández-Real, J. M., & Ricart, W. (2011). Osteocalcin: a new link between bone and energy metabolism. Some evolutionary clues. Current opinion in clinical nutrition and metabolic care, 14(4), 360–366. https://doi.org/10.1097/MCO.0b013e328346df4e

Ferron, M., & Lacombe, J. (2014). Regulation of energy metabolism by the skeleton: osteocalcin and beyond. Archives of biochemistry and biophysics, 561, 137–146. https://doi.org/10.1016/j.abb.2014.05.022

Ferron, M., Wei, J., Yoshizawa, T., Del Fattore, A., DePinho, R. A., Teti, A., Ducy, P., & Karsenty, G. (2010). Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell, 142(2), 296–308. https://doi.org/10.1016/j.cell.2010.06.003

Hinton P. S. (2016). Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility. Medical hypotheses, 93, 81–86. https://doi.org/10.1016/j.mehy.2016.05.008

Husain, A., & Jeffries, M. A. (2017). Epigenetics and Bone Remodeling. Current osteoporosis reports, 15(5), 450–458. https://doi.org/10.1007/s11914-017-0391-y

Hwang, Y. C., Jeong, I. K., Ahn, K. J., & Chung, H. Y. (2012). Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level. Osteoporosis International, 23(4), 1337-1342.

Johnson, R. W., Sims, N. A. (2014), Embedded in bone, but looking beyond: osteocalcin, epigenetics and ectopic bone formation. IBMS BoneKEy. 2014, 11, Article N 613. Report from the ASBMR 2014 Annual Meeting, Houston, TX, USA, 12–15 September 2014.

Kanazawa I. (2017). Interaction between bone and glucose metabolism [Review]. Endocrine journal, 64(11), 1043–1053. https://doi.org/10.1507/endocrj.EJ17-0323

Kulkarni, S. V., Meenatchi, S., Reeta, R., Ramesh, R., Srinivasan, A. R., & Lenin, C. (2017). Association of Glycemic Status with Bone Turnover Markers in Type 2 Diabetes Mellitus. International journal of applied & basic medical research, 7(4), 247–251. https://doi.org/10.4103/ijabmr.IJABMR_35_17

Kunutsor, S. K., Apekey, T. A., & Laukkanen, J. A. (2015). Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence. European journal of epidemiology, 30(8), 599–614. https://doi.org/10.1007/s10654-015-0058-x

Leclerc, N., Noh, T., Khokhar, A., Smith, E., & Frenkel, B. (2005). Glucocorticoids inhibit osteocalcin transcription in osteoblasts by suppressing Egr2/Krox20-binding enhancer. Arthritis and rheumatism, 52(3), 929–939. https://doi.org/10.1002/art.20872

Lee, B. H., & Stallcup, M. R. (2017). Glucocorticoid receptor binding to chromatin is selectively controlled by the coregulator Hic-5 and chromatin remodeling enzymes. The Journal of biological chemistry, 292(22), 9320–9334. https://doi.org/10.1074/jbc.M117.782607

Lee, N. K., Sowa, H., Hinoi, E., Ferron, M., Ahn, J. D., Confavreux, C., Dacquin, R., Mee, P. J., McKee, M. D., Jung, D. Y., Zhang, Z., Kim, J. K., Mauvais-Jarvis, F., Ducy, P., & Karsenty, G. (2007). Endocrine regulation of energy metabolism by the skeleton. Cell, 130(3), 456–469. https://doi.org/10.1016/j.cell.2007.05.047

Liu, C., Wo, J., Zhao, Q., Wang, Y., Wang, B., & Zhao, W. (2015). Association between Serum Total Osteocalcin Level and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 47(11), 813–819. https://doi.org/10.1055/s-0035-1564134

Ma, X. Y., Chen, F. Q., Hong, H., Lv, X. J., Dong, M., & Wang, Q. Y. (2015). The Relationship between Serum Osteocalcin Concentration and Glucose and Lipid Metabolism in Patients with Type 2 Diabetes Mellitus – The Role of Osteocalcin in Energy Metabolism. Annals of nutrition & metabolism, 66(2-3), 110–116. https://doi.org/10.1159/000370198

Meijsing S. H. (2015). Mechanisms of Glucocorticoid-Regulated Gene Transcription. Advances in experimental medicine and biology, 872, 59–81. https://doi.org/10.1007/978-1-4939-2895-8_3

Mizokami, A., Yasutake, Y., Higashi, S., Kawakubo-Yasukochi, T., Chishaki, S., Takahashi, I., Takeuchi, H., & Hirata, M. (2014). Oral administration of osteocalcin improves glucose utilization by stimulating glucagon-like peptide-1 secretion. Bone, 69, 68–79. https://doi.org/10.1016/j.bone.2014.09.006

Moseley K. F. (2012). Type 2 diabetes and bone fractures. Current opinion in endocrinology, diabetes, and obesity, 19(2), 128–135. https://doi.org/10.1097/MED.0b013e328350a6e1

Motyl, K. J., McCabe, L. R., & Schwartz, A. V. (2010). Bone and glucose metabolism: a two-way street. Archives of biochemistry and biophysics, 503(1), 2–10. https://doi.org/10.1016/j.abb.2010.07.030

Movahed, A., Larijani, B., Nabipour, I., Kalantarhormozi, M., Asadipooya, K., Vahdat, K., Akbarzadeh, S., Farrokhnia, M., Assadi, M., Amirinejad, R., Bargahi, A., & Sanjdideh, Z. (2012). Reduced serum osteocalcin concentrations are associated with type 2 diabetes mellitus and the metabolic syndrome components in postmenopausal women: the crosstalk between bone and energy metabolism. Journal of bone and mineral metabolism, 30(6), 683–691. https://doi.org/10.1007/s00774-012-0367-z

Napoli, N., Chandran, M., Pierroz, D. D., Abrahamsen, B., Schwartz, A. V., Ferrari, S. L., & IOF Bone and Diabetes Working Group (2017). Mechanisms of diabetes mellitus-induced bone fragility. Nature reviews. Endocrinology, 13(4), 208–219. https://doi.org/10.1038/nrendo.2016.153

Neve, A., Corrado, A., & Cantatore, F. P. (2013). Osteocalcin: skeletal and extra-skeletal effects. Journal of cellular physiology, 228(6), 1149–1153. https://doi.org/10.1002/jcp.24278

O'Brien, C. A., Jia, D., Plotkin, L. I., Bellido, T., Powers, C. C., Stewart, S. A., Manolagas, S. C., & Weinstein, R. S. (2004). Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology, 145(4), 1835–1841. https://doi.org/10.1210/en.2003-0990

Oldknow, K. J., MacRae, V. E., & Farquharson, C. (2015). Endocrine role of bone: recent and emerging perspectives beyond osteocalcin. The Journal of endocrinology, 225(1), R1–R19. https://doi.org/10.1530/JOE-14-0584

Otte, C., Hart, S., Neylan, T. C., Marmar, C. R., Yaffe, K., & Mohr, D. C. (2005). A meta-analysis of cortisol response to challenge in human aging: importance of gender. Psychoneuroendocrinology, 30(1), 80–91. https://doi.org/10.1016/j.psyneuen.2004.06.002

Patterson-Buckendahl P. (2011). Osteocalcin is a stress-responsive neuropeptide. Endocrine regulations, 45(2), 99–110. https://doi.org/10.4149/endo_2011_02_99

Petta, S., Amato, M., Cabibi, D., Cammà, C., Di Marco, V., Giordano, C., Galluzzo, A., & Craxì, A. (2010). Visceral adiposity index is associated with histological findings and high viral load in patients with chronic hepatitis C due to genotype 1. Hepatology (Baltimore, Md.), 52(5), 1543–1552. https://doi.org/10.1002/hep.23859

Pluijm, S. M., Visser, M., Smit, J. H., Popp-Snijders, C., Roos, J. C., & Lips, P. (2001). Determinants of bone mineral density in older men and women: body composition as mediator. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research, 16(11), 2142–2151. https://doi.org/10.1359/jbmr.2001.16.11.2142

Purnamasari, D., Puspitasari, M. D., Setiyohadi, B., Nugroho, P., & Isbagio, H. (2017). Low bone turnover in premenopausal women with type 2 diabetes mellitus as an early process of diabetes-associated bone alterations: a cross-sectional study. BMC endocrine disorders, 17(1), 72. https://doi.org/10.1186/s12902-017-0224-0

Reagan, M., Fairfield, H., Falank, C., Rosen, C. (2016). Bone Marrow Adiposity is Induced by the Osteocyte Derived Factor Sclerostin. ASBMR Annual Meeting 2016, Atlanta, Georgia, USA. OP N 1045.

Rui, X., Xu, B., Su, J., Pan, C., Zhan, C., Su, B., Li, H., Wang, J., Sheng, H., & Qu, S. (2014). Differential pattern for regulating insulin secretion, insulin resistance, and lipid metabolism by osteocalcin in male and female T2DM patients. Medical science monitor: international medical journal of experimental and clinical research, 20, 711–719. https://doi.org/10.12659/MSM.890130

Starup-Linde, J., Lykkeboe, S., Gregersen, S., Hauge, E. M., Langdahl, B. L., Handberg, A., & Vestergaard, P. (2016). Differences in biochemical bone markers by diabetes type and the impact of glucose. Bone, 83, 149–155. https://doi.org/10.1016/j.bone.2015.11.004

Starup-Linde, J., & Vestergaard, P. (2016). Biochemical bone turnover markers in diabetes mellitus - A systematic review. Bone, 82, 69–78. https://doi.org/10.1016/j.bone.2015.02.019

Sullivan, T. R., Duque, G., Keech, A. C., & Herrmann, M. (2013). An old friend in a new light: the role of osteocalcin in energy metabolism. Cardiovascular therapeutics, 31(2), 65–75. https://doi.org/10.1111/j.1755-5922.2011.00300.x

Terzi, R., Dindar, S., Terzi, H., & Demirtaş, Ö. (2015). Relationships among the metabolic syndrome, bone mineral density, bone turnover markers, and hyperglycemia. Metabolic syndrome and related disorders, 13(2), 78–83. https://doi.org/10.1089/met.2014.0074

Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2009). Diabetes and its complications and their relationship with risk of fractures in type 1 and 2 diabetes. Calcified tissue international, 84(1), 45–55. https://doi.org/10.1007/s00223-008-9195-5

Villafán-Bernal, J. R., Sánchez-Enríquez, S., & Muñoz-Valle, J. F. (2011). Molecular modulation of osteocalcin and its relevance in diabetes (Review). International journal of molecular medicine, 28(3), 283–293. https://doi.org/10.3892/ijmm.2011.706

Wallace, T. M., & Matthews, D. R. (2002). The assessment of insulin resistance in man. Diabetic medicine: a journal of the British Diabetic Association, 19(7), 527–534. https://doi.org/10.1046/j.1464-5491.2002.00745.x

Wei, J., Ferron, M., Clarke, C. J., Hannun, Y. A., Jiang, H., Blaner, W. S., & Karsenty, G. (2014). Bonespecific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. The Journal of clinical investigation, 124(4), 1–13. https://doi.org/10.1172/JCI72323

Wei, J., & Karsenty, G. (2015). An overview of the metabolic functions of osteocalcin. Reviews in endocrine & metabolic disorders, 16(2), 93–98. https://doi.org/10.1007/s11154-014-9307-7

Weinstein, R. S., Wan, C., Liu, Q., Wang, Y., Almeida, M., O'Brien, C. A., Thostenson, J., Roberson, P. K., Boskey, A. L., Clemens, T. L., & Manolagas, S. C. (2010). Endogenous glucocorticoids decrease skeletal angiogenesis, vascularity, hydration, and strength in aged mice. Aging cell, 9(2), 147–161. https://doi.org/10.1111/j.1474-9726.2009.00545.x

Yadav, V. K., Oury, F., Suda, N., Liu, Z. W., Gao, X. B., Confavreux, C., Klemenhagen, K. C., Tanaka, K. F., Gingrich, J. A., Guo, X. E., Tecott, L. H., Mann, J. J., Hen, R., Horvath, T. L., & Karsenty, G. (2009). A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell, 138(5), 976–989. https://doi.org/10.1016/j.cell.2009.06.051

Yan, W., & Li, X. (2013). Impact of diabetes and its treatments on skeletal diseases. Frontiers of medicine, 7(1), 81–90. https://doi.org/10.1007/s11684-013-0243-9

Yoshizawa T. (2011). [Bone remodeling and glucose/lipid metabolism] [Article in Japanese]. Clinical calcium, 21(5), 709–714.

Zanatta, L. C., Boguszewski, C. L., Borba, V. Z., & Kulak, C. A. (2014). Osteocalcin, energy and glucose metabolism. Arquivos brasileiros de endocrinologia e metabologia, 58(5), 444–451. https://doi.org/10.1590/0004-2730000003333

Zhou, H., Cooper, M. S., & Seibel, M. J. (2013). Endogenous Glucocorticoids and Bone. Bone research, 1(2), 107–119. https://doi.org/10.4248/BR201302001

Views:

368

Downloads:

252

Published
2020-05-31
Citations
How to Cite
Ковальчук А. В., Зиныч О. В., Корпачев В. В., Кушнарева Н. Н., & Прибила О. В. (2020). РОЛЬ МАРКЕРА КОСТНОГО РЕМОДЕЛИРОВАНИЯ ОСТЕОКАЛЬЦИНА В РЕГУЛЯЦИИ ЭНЕРГЕТИЧЕСКОГО ГОМЕОСТАЗА ПРИ САХАРНОМ ДИАБЕТЕ 2 ТИПА. World Science, 2(5(57), 20-29. https://doi.org/10.31435/rsglobal_ws/31052020/7077