Роль конечных продуктов гликирования в развитии и прогрессировании диабетической нейроостеоартропатии

Диабетическая нейроостеоартропатия (ДНОАП, стопа Шарко) является серьезным осложнением сахарного диабета, генез которого не окончательно изучен. Данная патология в большинстве случаев поздно диагностируется, что приводит к развитию тяжелых деформаций стопы вплоть до потери опороспособности конечности. Не существует единственной гипотезы формирования стопы Шарко, но есть факторы, предрасполагающие к ее развитию, а также ряд вероятных провоцирующих событий. Избыточное образование и накопление конечных продуктов гликирования (КПГ) может играть важную роль в патогенезе этого осложнения СД. КПГ — различные соединения, образующиеся в результате реакции между углеводами и свободными аминогруппами белков, липидов и нуклеиновых кислот без участия ферментов. Существуют различные факторы, которые приводят к накоплению КПГ в организме человека. Выделяют эндогенные и экзогенные факторы. К первым относятся определенные заболевания, такие как сахарный диабет, почечная недостаточность, ускоряющие процессы гликирования. К экзогенным факторам, приводящим к образованию продуктов липоокисления и гликоокисления, относятся табачный дым и длительная термическая обработка пищи.

В данном обзоре представлена информация о роли КПГ в развитии и прогрессировании осложнений у пациентов с сахарным диабетом.

1. Cho NH, Shaw JE, Karuranga S, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271-281. doi: https://doi.org/10.1016/j.diabres.2018.02.023

2. Токмакова А.Ю., Доронина Л.П., Галстян Г.Р., Сенюшкина Е.С., Митиш В.А. Отдаленные результаты комплексной терапии больной сахарным диабетом 2 типа и двусторонней нейроостеоартропатией. Раны и раневые инфекции // Журнал им. проф. Б.М. Костюченка. — 2018. — Т. 5. — №1. С. 39-49. doi: https://doi.org/10.25199/2408-9613-2018-5-1-39–49

3. Tesfaye S, Selvarajah D, Gandhi R, et al. Diabetic peripheral neuropathy may not be as its name suggests: Evidence from magnetic resonance imaging. Pain. 2016;157:S72-S80. doi: https://doi.org/10.1097/j.pain.0000000000000465

4. Ziegler D, Rathmann W, Dickhaus T, et al. Prevalence of polyneuropathy in prediabetes and diabetes is associated with abdominal obesity and macroangiopathy: The Monica/Kora Augsburg surveys S2 and S3. Diabetes Care. 2008;31(3):464-469. doi: https://doi.org/10.2337/dc07-1796

5. Callaghan BC, Xia R, Banerjee M, et al. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care. 2016;39(5):801-807. doi: https://doi.org/10.2337/dc16-0081

6. Lin YC, Lin CSY, Chang TS, et al. Early sensory neurophysiological changes in prediabetes. J Diabetes Investig. 2020;11(2):458-465. doi: https://doi.org/10.1111/jdi.13151

7. Bongaerts BWC, Rathmann W, Heier M, et al. Older subjects with diabetes and prediabetes are frequently unaware of having distal sensorimotor polyneuropathy: the KORA F4 study. Diabetes Care. 2013;36(5):1141-6. doi: https://doi.org/10.2337/dc12-0744

8. Kurisu S, Sasaki H, Kishimoto S, et al. Clinical polyneuropathy does not increase with prediabetes or metabolic syndrome in the Japanese general population. J Diabetes Investig. 2019;10(6):1565-1575. doi: https://doi.org/10.1111/jdi.13058

9. Kloska A, Korzon-Burakowska A, Malinowska M, et al. The role of genetic factors and monocyte-to-osteoclast differentiation in the pathogenesis of Charcot neuroarthropathy. Diabetes Res Clin Pract. 2020;166. doi: https://doi.org/10.1016/j.diabres.2020.108337

10. Rogers LC, Frykberg RG, Armstrong DG, et al. The Charcot foot in diabetes. Diabetes Care. 2011;34(9):2123-2129. doi: https://doi.org/10.2337/dc11-0844

11. Armstrong DG, Peters EJG. Charcot’s arthropathy of the foot. J Am Podiatr Med Assoc. 2002;92(7):390-394. doi: https://doi.org/10.7547/87507315-92-7-390

12. Frykberg RG, Belczyk R. Epidemiology of the Charcot Foot. Clin Podiatr Med Surg. 2008;25(1):17-28. doi: https://doi.org/10.1016/j.cpm.2007.10.001

13. Salini D, Harish K, Minnie P, et al. Prevalence of Charcot arthropathy in Type 2 diabetes patients aged over 50 years with severe peripheral neuropathy: A retrospective study in a Tertiary Care South Indian Hospital. Indian J Endocrinol Metab. 2018;22(1):107-111. doi: https://doi.org/10.4103/ijem.IJEM_257_17

14. Miller DS, William Miller WF. Lichtman,Diabetic neuropathic arthropathy of feet. Published online 1965: 530.

15. McEwen LN, Ylitalo KR, Herman WH, Wrobel JS. Prevalence and risk factors for diabetes-related foot complications in Translating Research into Action for Diabetes (TRIAD).J.Diabetes.Complications.2013;27(6):588-592. doi: https://doi.org/10.1016/j.jdiacomp.2013.08.003

16. Younis B Bin, Shahid A, Arshad R, et al. Charcot osteoarthropathy in type 2 diabetes persons presenting to specialist diabetes clinic at a tertiary care hospital. BMC Endocr Disord. 2015;15(1):1-5. doi: https://doi.org/10.1186/s12902-015-0023-4

17. Jeffcoate WJ, Game F, Cavanagh PR. The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet. 2005;366(9502):2058-2061. doi: https://doi.org/10.1016/S0140-6736(05)67029-8

18. Baker N, Green A, Krishnan S, et al. Microvascular and C-fiber function in diabetic charcot neuroarthropathy and diabetic peripheral neuropathy. Diabetes Care. 2007;30(12):3077-3079. doi: https://doi.org/10.2337/dc07-1063

19. Trieb K. The Charcot foot: Pathophysiology, diagnosis and classification. Bone Jt J. 2016;98-B(9):1155-1159. doi: https://doi.org/10.1302/0301-620X.98B9.37038

20. Jansen RB, Christensen TM, Bülow J, et al. Markers of Local Inflammation and Bone Resorption in the Acute Diabetic Charcot Foot. J Diabetes Res. 2018;2018. doi: https://doi.org/10.1155/2018/5647981

21. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118(2):503-508. doi: https://doi.org/10.1378/chest.118.2.503

22. GROSE SWAR. Regulation of wound healing by growth factors and cytokines. Wound Heal Process Phases Promot. Published online 2003:73-93.

23. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008;473(2):139-146. doi: https://doi.org/10.1016/j.abb.2008.03.018

24. Mountzios G, Dimopoulos MA, Bamias A, et al. Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton. Acta Oncol (Madr). 2007;46(2):221-229. doi: https://doi.org/10.1080/02841860600635870

25. Silva I, Branco JC. Rank/RANKL/OPG: Literature review. Acta Reumatol Port. 2011;36(3):209-218.

26. Mascarenhas JV, Jude EB. The Charcot Foot as a Complication of Diabetic Neuropathy. Curr Diab Rep. 2014;14(12):1-9. doi: https://doi.org/10.1007/s11892-014-0561-6

27. Wautier JL, Schmidt AM. Protein glycation: A firm link to endothelial cell dysfunction. Circ Res. 2004;95(3):233-238. doi: https://doi.org/10.1161/01.RES.0000137876.28454.64

28. Zieman SJ, Kass DA. Advanced glycation endproduct crosslinking in the cardiovascular system: Potential therapeutic target for cardiovascular disease. Drugs. 2004;64(5):459-470. doi: https://doi.org/10.2165/00003495-200464050-00001

29. Bastien P. Aged Human Skin is More Susceptible than Young Skin to Accumulate Advanced Glycoxidation Products Induced by Sun Exposure. J Aging Sci. 2013;01(03):1-5. doi: https://doi.org/10.4172/2329-8847.1000112

30. Fishman SL, Sonmez H, Basman C, et al. The role of advanced glycation end-products in the development of coronary artery disease in patients with and without diabetes mellitus: A review. Mol Med. 2018;24(1):1-12. doi: https://doi.org/10.1186/s10020-018-0060-3

31. Koyama Y, Takeishi Y, Arimoto T, et al. High Serum Level of Pentosidine, an Advanced Glycation End Product (AGE), is a Risk Factor of Patients with Heart Failure. J Card Fail. 2007;13(3):199-206. doi: https://doi.org/10.1016/j.cardfail.2006.11.009

32. Bidasee KR, Zhang Y, Shao CH, et al. Diabetes Increases Formation of Advanced Glycation End Products on Sarco(endo)plasmic Reticulum Ca2+-ATPase. Diabetes. 2004;53(2):463-473. doi: https://doi.org/10.2337/diabetes.53.2.463

33. Yan SF, Ramasamy R, Schmidt AM. The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease. Expert Rev Mol Med. 2009;11(March):1-13. doi: https://doi.org/10.1017/S146239940900101X

34. Potekhina Y. Collagen Structure and Function. Russ Osteopath J. 2016;(1-2):87-99. doi: https://doi.org/10.32885/2220-0975-2016-1-2-87-99

35. Bishop JE, Rhodes S, Laurent GJ, Low RB. Increased collagen synthesis and decreased collagen degradation in right ventricular hypertrophy induced by pressure overload. Published online 1994:1581-1585.

36. Saito M, Soshi S, Fujii K. Effect of hyper- and microgravity on collagen post-translational controls of MC3T3-E1 osteoblasts. J Bone Miner Res. 2003;18(9):1695-1705. doi: https://doi.org/10.1359/jbmr.2003.18.9.1695

37. Shiraki M, Urano T, Kuroda T, et al. The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures. J Bone Miner Metab. 2008;26(6):595-602. doi: https://doi.org/10.1007/s00774-008-0878-9

38. Kanazawa I. Interaction between bone and glucose metabolism. Endocr J. 2017;64(11):1043-1053. doi: https://doi.org/10.1507/endocrj.EJ17-0323

39. Portero-otín M, Pamplona R, Ruiz MC, Cabiscol E, Prat J, Bellmunt MJ. Diabetes Induces an Impairment in the Proteolytic Activity Against Oxidized Proteins and a Heterogeneous Effect in Nonenzymatic Protein Modifications in the Cytosol of Rat Liver and Kidney. :2215-2220.

40. Karim L, Tang SY, Sroga GE, et al. Differences in non-enzymatic glycation and collagen cross-links between human cortical and cancellous bone. Osteoporos Int. 2013;24(9):2441-2447. doi: https://doi.org/10.1007/s00198-013-2319-4

41. Saito M, Fujii K, Mori Y, et al. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int. 2006;17(10):1514-1523. doi: https://doi.org/10.1007/s00198-006-0155-5

42. Schwartz A V., Garnero P, Hillier TA, et al. Pentosidine and increased fracture risk in older adults with type 2 diabetes. J Clin Endocrinol Metab. 2009;94(7):2380-2386. doi: https://doi.org/10.1210/jc.2008-2498

43. Shiraki M, Kuroda T, Tanaka S, et al. Nonenzymatic collagen cross-links induced by glycoxidation (pentosidine) predicts vertebral fractures. J Bone Miner Metab. 2008;26(1):93-100. doi: https://doi.org/10.1007/s00774-007-0784-6

44. Yamamoto M, Yamaguchi T, Yamauchi M, et al. Serum pentosidine levels are positively associated with the presence of vertebral fractures in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab. 2008;93(3):1013-1019. doi: https://doi.org/10.1210/jc.2007-1270

45. Farlay D, Armas LAG, Gineyts E, et al. Nonenzymatic Glycation and Degree of Mineralization Are Higher in Bone from Fractured Patients with Type 1 Diabetes Mellitus. J Bone Miner Res. 2016;31(1):190-195. doi: https://doi.org/10.1002/jbmr.2607

46. Schmidt AM, Yan S Du, Yan SF, et al. The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta - Mol Cell Res. 2000;1498(2-3):99-111. doi: https://doi.org/10.1016/S0167-4889(00)00087-2

47. Lee EJ, Park JH. Receptor for Advanced Glycation Endproducts (RAGE), Its Ligands, and Soluble RAGE: Potential Biomarkers for Diagnosis and Therapeutic Targets for Human Renal Diseases. Genomics Inform. 2013;11(4):224. doi: https://doi.org/10.5808/gi.2013.11.4.224

48. Ott C, Jacobs K, Haucke E, et al. Role of advanced glycation end products in cellular signaling. Redox Biol. 2014;2(1):411-429. doi: https://doi.org/10.1016/j.redox.2013.12.016

49. Xue J, Manigrasso M, Scalabrin M, et al. Change in the Molecular Dimension of a RAGE-Ligand Complex Triggers RAGE Signaling. Structure. 2016;24(9):1509-1522. doi: https://doi.org/10.1016/j.str.2016.06.021

50. Goldin A, Beckman JA, Schmidt AM, et al. Advanced glycation end products: Sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597-605. doi: https://doi.org/10.1161/CIRCULATIONAHA.106.621854

51. Wautier JL, Wautier MP, Schmidt AM, et al. Advanced glycation end products (AGEs) on the surface of diabetic erythrocytes bind to the vessel wall via a specific receptor inducing oxidant stress in the vasculature: A link between surface-associated AGEs and diabetic complications. Proc Natl Acad Sci U S A. 1994;91(16):7742-7746. doi: https://doi.org/10.1073/pnas.91.16.7742

52. Nilforoushan D, Gramoun A, Glogauer M, et al. Nitric oxide enhances osteoclastogenesis possibly by mediating cell fusion. Nitric Oxide - Biol Chem. 2009;21(1):27-36. doi: https://doi.org/10.1016/j.niox.2009.04.002

53. Nowak WN, Borys S, Kusińska K, et al. Number of circulating pro-angiogenic cells, growth factor and anti-oxidative gene profiles might be altered in type 2 diabetes with and without diabetic foot syndrome. J Diabetes Investig. 2014;5(1):99-107. doi: https://doi.org/10.1111/jdi.12131

54. Hegab Z. Role of advanced glycation end products in cardiovascular disease. World J Cardiol. 2012;4(4):90. doi: https://doi.org/10.4330/wjc.v4.i4.90

55. Stirban A, Gawlowski T, Roden M. Vascular effects of advanced glycation endproducts: Clinical effects and molecular mechanisms. Mol Metab. 2014;3(2):94-108. doi: https://doi.org/10.1016/j.molmet.2013.11.006

56. Saremi A, Howell S, Schwenke DC, et al. Advanced glycation end products, oxidation products, and the extent of atherosclerosis during the VA diabetes trial and follow-up study. Diabetes Care. 2017;40(4):591-598. doi: https://doi.org/10.2337/dc16-1875

57. Oldfield MD, Bach LA, Forbes JM, et al. Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest. 2001;108(12):1853-1863. doi: https://doi.org/10.1172/JCI11951

58. Rabbani N, Thornalley PJ. Glyoxalase 1 modulation in obesity and diabetes. Antioxidants Redox Signal. 2019;30(3):354-374. doi: https://doi.org/10.1089/ars.2017.7424

59. Giacco F, Du X, D’Agati VD, et al. Knockdown of glyoxalase 1 mimics diabetic nephropathy in nondiabetic mice. Diabetes. 2014;63(1):291-299. doi: https://doi.org/10.2337/db13-0316