ENHANCED CIRCULATORY LEVELS OF OSTEOPROTEGERIN IN TYPE 2 DIABETES MELLITUS PATIENTS: ASSOCIATION WITH METABOLIC AND HORMONAL DYSBALANCE PARAMETERS, VASCULAR COMPLICATIONS PATTERN

Authors

DOI:

https://doi.org/10.21856/j-PEP.2012.1.01

Keywords:

osteoprotegerin, type 2 diabetes mellitus, insulin resistance, atherogenesis markers

Abstract

61 middle-age overweight or obese patients with type 2 diabetes mellitus were studied. Patients were characterized by hormonal and metabolic parameters of insulin resistance (fasting hyperinsulinemia, both enhanced HOMA-IR indices and circulating free fatty acids levels, hypoadiponectinemia, hypertriglyceridemia). It was revealed significant increase in the circulating levels of osteoprotegerin, associated with macrovascular complications (ischemic heart disease, essential hypertension). It was also shown positive correlation of osteoprotegerin with retinol-binding protein 4, fetuin-A and progranulin. Our data support the perspective of circulating osteoprotegerin as new cardiovascular risk factor.

References

Osteoprotegerin: a novel secreted protein involved in the regulation of bone density [Text] / W. S. Simonet, D. L. Lacey, C. R. Dunstan [et al.] // Cell. —1997. — Vol. 89. — P. 309–319.

Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis [Text] / E. Tsuda, M. Goto, S. Mochizuki [et al.] // Biochem. Bioph. Res. Comm. — 1997. — Vol. 234. — P. 137–142.

TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption [Text] / B. S. Kwon, S. Wang, N. Udagawa [et al.] // FASEB J. — 1998. — Vol. 12. — P. 845–854.

Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation [Text] / D. L. Lacey, E. Timms, H. L. Tan [et al.] // Cell. —1998. — Vol. 93. — P. 165–176.

Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand [Text] / H. Hsu, D. L. Lacey, C. R. Dunstan [et al.] // Proc. Natl. Acad. Sci. — 1999. — Vol. 96. — P. 3540–3545.

Hofbauer, L. C. The role of receptor activator of nuclear factor-κB ligand and osteoprogerin in pathogenesis and treatment of metabolic bone disease [Text] / L. C. Hofbauer, A. E. Heufelder // J. Clin. Endocrinol. Metabol. — 2000. — Vol. 85. — P. 2355–2363.

RANKL-RANK signaling in osteoclastogenesis and bone disease [Text] / T. Wada, T. Nakashima, N. Hiroshi [et al.] // Trends. Mol. Med. — 2006. — Vol. 12. — P. 17–25.

A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function [Text] / D. M. Anderson, E. Marakovsky, W. L. Billingsley [et al.] // Nature. — 1997. — Vol. 390. — P. 175–179.

OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis [Text] / Y. Y. Kong, H. Yoshida, I. Sarosi [et al.] // Nature. — 1999. — Vol. 397. — P. 315–323.

Kong, Y. Y. Osteoprotegerin ligand: a regulator of immune responses and bone physiology [Text] / Y. Y. Kong, W. J. Boyle, J. M. Penninger // Immunol. Today. — 2000. — Vol. 21. — P. 495–502.

Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL [Text] / J. G. Emery, P. McDonnell, M. B. Burke [et al.] // J. Biol. Chem. — 1998. — Vol. 273. — P. 14363–14367.

Osteoprotegerin is an αvβ3-induced NF-κB-dependent survival factor for endothelial cells [Text] / U. M. Malyankar, M. Scatena, K. L. Suchland [et al.] // J. Biol. Chem. — 2000. — Vol. 275. — P. 20959–20962.

Receptor activator of NF-κB and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis [Text] / P. Collin-Osdoby, L. Rothe, F. Anderson [et al.] // J. Biol. Chem. — 2001. — Vol. 276. — P. 20659–20672.

Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells [Text] / L. C. Hofbauer, C. Shui, B. L. Riggs [et al.] // Biochem. Biophys. Res. Commun. — 2001. — Vol. 280. — P. 334–339.

Olesen, P. Arterial osteoprotegerin: increased amounts in diabetes and modifiable synthesis from vascular smooth muscle cells by insulin and TNFalpha [Text] / P. Olesen, T. Ledet, L. M. Rasmussen // Diabetologia. — 2005. — Vol. 48. — P. 561–568.

Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification [Text] / N. Bucay, I. Sarosi, C. R. Dunstan [et al.] // Genes Dev. — 1998. — Vol. 12. — P. 1260–1268.

Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease [Text] / S. Jono, Y. Ikari, A. Shioi [et al.] // Circulation. — 2002. — Vol. 106. — P. 1192–1194.

Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications (Erratum) [Text] / S. T. Knudsen, C. H. Foss, P. L. Poulsen [et al.] // Europ. J. Endocrinol. — 2003. — Vol. 149. — P. 161.

Increased osteoprotegerin serum levels in men with coronary artery disease [Text] / M. Schoppet, A. M. Sattler, J. R. Schaefer [et al.] // J. Clin. Endocrinol. Metabol. — 2003. — Vol. 88. — P. 1024–1028.

Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease [Text] / S. Kiechi, G. Schett, G. Wenning [et al.] // Circulation. — 2004. — Vol. 109. — P. 2175–2180.

Browner, W. S. Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women [Text] / W. S. Browner, L. Y. Lui, S. R. Cummings // J. Clin. Endocrinol. Metabol. — 2001. —Vol. 86. — P. 631–637.

Collin-Osdoby, P. Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin [Text] / P. Collin-Osdoby // Circ. Res. — 2004. — Vol. 95. — P. 1046–1057.

Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients [Text] / A. Avignon, A. Sultan, C. Piot [et al.] // Diabetes Care. — 2005. —Vol. 28. — № 9. — P. 2176–2180.

Osteoprotegerin: a novel independent marker for silent myocardial ischemia in asymptomatic diabetic patients [Text] / A. Avignon, A. Sultan, C. Piot [et al.] // Diabetes Care. — 2007. — Vol. 30. —P. 3934–3939.

Osteoprotegerin, thiazolidinediones treatment, and silent myocardial ischemia in type 2 diabetic patients [Text] / A. Sultan, A. Avignon, F. Galtier [et al.] // Diabetes Care. — 2008. — Vol. 31. — P. 593–595.

Atherosclerosis: basic mechanisms. Oxidation, in-flammation, and genetics [Text] / J. A. Berliner, M. Navab, A. M. Fogelman [et al.] // Circulation. —1995. — Vol. 91. — P. 2488–2496.

Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus [Text] / S. Lehto, L. Niskanen, M. Suhonen [et al.] // Arterioscler. Thromb. Vasc. Biol. — 1996. — Vol. 16. — P. 978–983.

Hofbauer, L. C. Osteoprotegerin: a link between osteoporosis and arterial calcification? [Text] / L. C. Hofbauer, M. Schoppet // Lancet. — 2001. — Vol. 358. — P. 257–259.

Nybo, M. Osteoprotegerin released from the vascular wall from vascular smooth muscle cells [Text] / M. Nybo, L. M. Rasmussen // Atherosclerosis. — 2008. — Vol. 201. — P. 33–35.

Low blood osteoprotegerin levels are a predictor to poor prognosis in Japanese patients on hemodialysis due to diabetic nephropathy [Text] / K. Yokoyama, T. Shigematsu, K. Miyaki [et al.] // Therapeutic Apheresis and Dialysis. — 2008. — Vol. 12. —P. 259–260.

Jorgensen, G. M. Acute hyperinsulinemia decreases plasma osteoprotegerin with diminished effect in type 2 diabetes and obesity [Text] / G. M. Jorgensen, B. Vind, M. Nybo // Europ. J. Endocrinol. —2009. — Vol. 161. — P. 95–101.

Kannel, W. B. Diabetes and cardiovascular disease; the Framingham study [Text] / W. B. Kannel, D. L. McGee // J. Am. Med. Ass. — 1979. —Vol. 241. — P. 2035–2038.

Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2 diabetes [Text] / F. B. Hu, M. J. Stampfer, S. M. Haffner // Diabetes Care. —2002. — Vol. 25. — № 7. — P. 1129–1134.

Increased circulating levels of osteoclastogenesis-inhibitory factor (osteoprotegerin) in patients with chronic renal failure [Text] / J. J. Kazama, T. Shigematsu, K. Yano [et al.] // Am. J. Kidney. Dis. —2002. — Vol. 39. — P. 525–532.

Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status [Text] / P. Szulc, L. C. Hofbauer, A. E. Heufelder [et al.] // J. Clin. Endocrinol. Metabol. — 2001. —Vol. 86. — P. 3162–3165.

Costantini, D. On the measurement of circulating antioxidant capacity and the nightmare of uric acid [Text] / D. Costantini // Meth. Ecol. Evol. —2011. — Vol. 2. — P. 321–325.

Schell, Th. Oxidative stress, implications in equine orthopedic disease, insulin resistance and a potential target for therapy [Text] / Th. Schell, C. Neatu // JAHYMA. — 2010. — Vol. 29. — № 1. — P. 11–15.

Richter, R. Determination of paraoxonase (pon 1) status requires more than genotyping [Text] / R. Richter, C. E. Furlong // Pharmacogenetics. —1999. — Vol. 9. — P. 745–753.

Matthews, D. R. Homeostasis model assessement: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man [Text] / D. R. Matthews, J. P. Hosker, A. S. Rudenski // Diabetologia. — 1985. — Vol. 28. — P. 412–419.

Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans [Text] / A. Katz, S. S. Nambi, K. Mather [et al.] // J. Clin. Endocrinol. Metabol. — 2000. —Vol. 85. — P. 2402–2410.

Osteoprotegerin in relation to body weight, lipid parameters insulin sensitivity, adipocytokines, and C-reactive protein in obese and non-obese young individuals: results from both cross-sectional and interventional study [Text] / M. H. Gannage-Yared, C. Yaghi, B. Habre [et al.] // Europ. J. Endocrinol. — 2008. — Vol. 158. — P. 353–359.

Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population [Text] / M. H. Gannage-Yared, F. Fares, M. Semaan [et al.] // Clin. Endocrinol. — 2006. — Vol. 64. — P. 652–658.

Inflammatory mediators in morbidly obese subjects: associations with glucose abnormalities and changes after oral glucose [Text] / D. Hofso, T. Ueland, H. Hager [et al.] // Europ. J. Endocrinol. — 2009. —Vol. 161. — P. 451–458.

Effect of pioglitazone on serum concentrations of osteoprotegerin in patients with type 2 diabetes mellitus [Text] / J. S. Park, M. H. Cho, J. S. Nam [et al.] // Europ. J. Endocrinol. — 2011. — Vol. 164. —№ 1. — P. 69–74.

Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signalling pathway [Text] / X. H. Luo, L. J. Guo, H. Xie [et al.] // J. Bon. Min. Res. — 2006. –Vol. 21. — P. 1648–1658.

Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity [Text] / S. M. Kim, J. Lee, O. H. Ryu [et al.] // Clin. Endocrinol. — 2005. — Vol. 63. — P. 594–598.

The relationship between plasma osteoprotegerin and endothelium dependent arterial dilatation in type 2 diabetes [Text] / G. D. Xiang, L. Xu, L. S. Zhao [et al.] // Diabetes. — 2006. — Vol. 55. —P. 2126–2131.

Boneti, P. O. Endothelial dysfunction, a marker of atherosclerotic risk [Text] / P. O. Boneti, L. O. Lerman, A. Lerman // Arterioscl. Thromb. Vascul. Biol. — 2003. — Vol. 23. — P. 168–175.

Downloads

Published

2012-03-15

How to Cite

Gorshunska, M. (2012). ENHANCED CIRCULATORY LEVELS OF OSTEOPROTEGERIN IN TYPE 2 DIABETES MELLITUS PATIENTS: ASSOCIATION WITH METABOLIC AND HORMONAL DYSBALANCE PARAMETERS, VASCULAR COMPLICATIONS PATTERN. Problems of Endocrine Pathology, 39(1), 5-15. https://doi.org/10.21856/j-PEP.2012.1.01

Issue

Section

CLINICAL ENDOCRINOLOGY

Most read articles by the same author(s)

1 2 > >>