Endocrinol Metab.  2012 Dec;27(4):289-294. 10.3803/EnM.2012.27.4.289.

The Association between Serum Endogenous Secretory Receptor for Advanced Glycation End Products and Vertebral Fractures in Type 2 Diabetes

Affiliations
  • 1Department of Internal Medicine, Myongji Hospital, Kwandong University College of Medicine, Goyang, Korea. bonesh@naver.com

Abstract

BACKGROUND
Patients with type 2 diabetes are known to have an increased risk for osteoporotic fractures compared with non-diabetic subjects. We investigated whether the serum endogenous secretory receptor for advanced glycation end products (esRAGE) or pentosidine was associated with prevalent vertebral fractures in patients with type 2 diabetes.
METHODS
We enrolled 140 patients with type 2 diabetes mellitus (73 men aged 50 or older and 67 postmenopausal women). Lateral X-ray films of the spine revealed prevalent vertebral fractures. The serum concentration of esRAGE and pentosidine were measured.
RESULTS
The mean age of all patients was 66.2 +/- 6.5 years and 22% of patients had prevalent vertebral fractures. Serum pentosidine levels were similar between those with and without vertebral fractures. There were no significant correlations between serum esRAGE levels and age, body mass index, duration of diabetes, and hemoglobin A1c. However, patients with moderate or severe vertebral fractures have a lower esRAGE level compared to those without after adjusting for age and gender (0.33 +/- 0.12 ng/mL vs. 0.24 +/- 0.03 ng/mL, P < 0.05). Logistic regression analysis demonstrated that patients in the lowest tertile of esRAGE had a higher risk of moderate or severe vertebral fractures (odds ratio, 16.6; 95% confidence interval, 1.4-198.5) than patients in the highest tertile.
CONCLUSION
These results revealed that a low esRAGE level was independently associated with moderate or severe vertebral fractures in type 2 diabetic patients.

Keyword

Diabetes mellitus; esRAGE; Osteoporosis; Pentosidine; Spinal fracture

MeSH Terms

Aged
Arginine
Body Mass Index
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glycosylation End Products, Advanced
Hemoglobins
Humans
Logistic Models
Lysine
Male
Osteoporosis
Osteoporotic Fractures
Spinal Fractures
Spine
X-Ray Film
Arginine
Glycosylation End Products, Advanced
Hemoglobins
Lysine

Figure

  • Fig. 1. Serum endogenous secretory receptor for advanced glycation end products (esRAGE) concentration in type 2 diabetic patients with or without vertebral fractures after adjusting for age and gender. Patients with moderate or severe vertebral fractures showed significantly lower esRAGE levels compared to those without. ∗Age, gender adjusted P < 0.05.


Reference

1. Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes: a metaanalysis. Osteoporos Int. 18:427–444. 2007.
2. Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 166:495–505. 2007.
Article
3. Yamamoto M, Yamaguchi T, Yamauchi M, Kaji H, Sugimoto T. Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. J Bone Miner Res. 24:702–709. 2009.
Article
4. Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 46:223–234. 1995.
5. Rix M, Andreassen H, Eskildsen P. Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care. 22:827–831. 1999.
Article
6. Schwartz AV, Vittinghoff E, Sellmeyer DE, Feingold KR, de Rekeneire N, Strotmeyer ES, Shorr RI, Vinik AI, Odden MC, Park SW, Faulkner KA, Harris TB; Health, Aging, and Body Composition Study. Diabetes-related complications, glycemic control, and falls in older adults. Diabetes Care. 31:391–396. 2008.
Article
7. Schwartz AV, Hillier TA, Sellmeyer DE, Resnick HE, Gregg E, Ensrud KE, Schreiner PJ, Margolis KL, Cauley JA, Nevitt MC, Black DM, Cum-mings SR. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care. 25:1749–1754. 2002.
8. McCarthy TL, Centrella M, Canalis E. Insulin-like growth factor (IGF) and bone. Connect Tissue Res. 20:277–282. 1989.
Article
9. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T. Serum insulin-like growth factor-I level is associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes mellitus. Osteoporos Int. 18:1675–1681. 2007.
Article
10. Saito M, Fujii K, Mori Y, Marumo K. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontane-ously diabetic WBN/Kob rats. Osteoporos Int. 17:1514–1523. 2006.
Article
11. Yamamoto M, Yamaguchi T, Yamauchi M, Yano S, Sugimoto T. Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab. 93:1013–1019. 2008.
Article
12. Ding KH, Wang ZZ, Hamrick MW, Deng ZB, Zhou L, Kang B, Yan SL, She JX, Stern DM, Isales CM, Mi QS. Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss. Biochem Biophys Res Commun. 340:1091–1097. 2006.
Article
13. Ogawa N, Yamaguchi T, Yano S, Yamauchi M, Yamamoto M, Sugimoto T. The combination of high glucose and advanced glycation endproducts (AGEs) inhibits the mineralization of osteoblastic MC3T3-E1 cells through glucose-induced increase in the receptor for AGEs. Horm Metab Res. 39:871–875. 2007.
Article
14. Yonekura H, Yamamoto Y, Sakurai S, Petrova RG, Abedin MJ, Li H, Yasui K, Takeuchi M, Makita Z, Takasawa S, Okamoto H, Watanabe T, Yamamoto H. Novel splice variants of the receptor for advanced glycation endproducts expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 370(Pt 3):1097–1109. 2003.
Article
15. Wautier JL, Zoukourian C, Chappey O, Wautier MP, Guillausseau PJ, Cao R, Hori O, Stern D, Schmidt AM. Receptor-mediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest. 97:238–243. 1996.
Article
16. Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM. Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med. 4:1025–1031. 1998.
Article
17. Genant HK, Wu CY, Van Kuijk C, Nevitt MC. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res. 8:1137–1148. 1993.
Article
18. Dominguez LJ, Barbagallo M, Moro L. Collagen overglycosylation: a bio-chemical feature that may contribute to bone quality. Biochem Biophys Res Commun. 330:1–4. 2005.
Article
19. Yamamoto M, Yamaguchi T, Yamauchi M, Sugimoto T. Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care. 32:2263–2268. 2009.
Article
20. Inaba M, Okuno S, Kumeda Y, Yamakawa T, Ishimura E, Nishizawa Y. Increased incidence of vertebral fracture in older female hemodialyzed patients with type 2 diabetes mellitus. Calcif Tissue Int. 76:256–260. 2005.
Article
21. Nisbeth U, Lindh E, Ljunghall S, Backman U, Fellström B. Increased fracture rate in diabetes mellitus and females after renal transplantation. Transplantation. 67:1218–1222. 1999.
22. Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res. 12:283–289. 1997.
Article
23. Hadjidakis D, Diammantopoulos E, Kokkinakis E, Sfakianakis M, Mera-kos G, Raptis SA. Bone mineral density in type II diabetics with macroan-giopathy. J Bone Miner Res. 12(Suppl 1):S516. 1997.
24. McNair P, Madsbad S, Christensen MS, Christiansen C, Faber OK, Binder C, Transbol I. Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis. Acta Endocrinol (Copenh). 90:463–472. 1979.
Article
25. McNair P, Christensen MS, Madsbad S, Christiansen C, Transb⊘l I. Hypo-parathyroidism in diabetes mellitus. Acta Endocrinol (Copenh). 96:81–86. 1981.
Article
26. Katakami N, Matsuhisa M, Kaneto H, Matsuoka TA, Sakamoto K, Yasu-da T, Umayahara Y, Kosugi K, Yamasaki Y. Serum endogenous secretory RAGE level is an independent risk factor for the progression of carotid atherosclerosis in type 1 diabetes. Atherosclerosis. 204:288–292. 2009.
Article
27. Lu L, Pu LJ, Zhang Q, Wang LJ, Kang S, Zhang RY, Chen QJ, Wang JG, De Caterina R, Shen WF. Increased glycated albumin and decreased es-RAGE levels are related to angiographic severity and extent of coronary artery disease in patients with type 2 diabetes. Atherosclerosis. 206:540–545. 2009.
Article
28. Peng WH, Lu L, Hu J, Yan XX, Zhang Q, Zhang RY, Chen QJ, Shen WF. Decreased serum esRAGE level is associated with angiographically determined coronary plaque progression in diabetic patients. Clin Biochem. 42:1252–1259. 2009.
Article
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