Метаболический синдром как протромбогенноеи провоспалительное состояние: влияниетерапевтических мероприятий

В обзоре освещены основные аспекты влияния терапевтических мероприятий на провоспалительные и прокоагулянтные нарушения, сопутствующие метаболическому синдрому. Основополагающее место в коррекции указанных патологических сдвигов занимает немедикаментозное лечение (рациональное питание и физические нагрузки). Кроме того, в ряде случаев целесообразной является медикаментозная терапия, направленная на снижение инсулинорезистентности, учитывая, что препараты, улучшающие чувствительность к инсулину, - метформин и тиазолидиндионы - обладают целым рядом других
положительных свойств, в том числе способствуют снижению воспалительных и коагуляционных сдвигов.

метаболический синдром, провоспалительные цитокины, прокоагулянтное состояние, метформин, тиазолидиндионы

1. Kopelman P.G. Obesity as a medical problem // Nature. 2000 Apr. 6; 404(6778): 635-43.

2. Lau D.C., Schillabeer G., Li Z.H., Wong K.L., Varzaneh F.E., Tough S.C. Paracrine interactions in adipose tissue development and growth // Int. J. Obes. Relat. Metab. Disord. 1996 Mar.; 20 Suppl. 3: S. 16-25.

3. Mohamed-Ali V., Pinkney J.H., Coppack S.W. Adipose tissue as an endocrine and paracrine organ // Int. J. Obes. Relat. Metab. Disord. 1998 Dec.; 22(12): 1145-58.

4. Barinas-Mitchell E., Kuller L.H., Sutton-Tyrrell K., Hegazi R., Harper P., Mancino J., Kelley D.E. Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes // Diabetes Care. 2006 Oct.; 29(10): 2218-22.

5. Esposito K., Pontillo A., Di Palo C., Giugliano G., Masella M., Marfella R., and Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial // JAMA 2003; 289: 1799-804.

6. Heilbronn L.K., Noakes M., and Clifton P.M. Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women // Arterioscler. Thromb. Vasc. Biol. 2001; 21: 968-70.

7. Kopp H.P., Kopp C.W., Festa A., Krzyzanowska K., Kriwanek S., Minar E., Roka R., and Schernthaner G. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients // Arterioscler. Thromb. Vasc. Biol. 2003; 23: 1042-7.

8. Tchernof A., Nolan A., Sites C.K., Ades P.A., and Poehlman E.T. Weight loss reduces C-reactive protein levels in obese postmenopausal women // Circulation 2002; 105: 564-9.

9. Mertens I., Van Gaal L.F. Obesity, haemostasis and the fibrinolytic system // Obes. Rev. 2002 May; 3(2): 85-101.

10. Sola E., Vaya A., Espaсa F., Castellу R., Ramуn L.A., Hernбndez-Mijares A., Vicente V., Estellйs A. Plasminogen activator inhibitor-1 levels in severe and morbid obesity. Effect of weight loss and influence of 4G/5G polymorphism // Thromb. Res. 2008; 122(3): 320-7.

11. Hankey C.R., Lean M.E., Lowe G.D., Rumley A., Woodward M. Effects of moderate weight loss on anginal symptoms and indices of coagulation and fibrinolysis in overweight patients with angina pectoris // Eur. J. Clin. Nutr. 2002 Oct.; 56(10): 1039-45.

12. Rissanen P., Vahtera E., Krusius T., Uusitupa M., Rissanen A. Weight change and blood coagulability and fibrinolysis in healthy obese women // Int. J. Obes. Relat. Metab. Disord. 2001 Feb.; 25(2): 212-8.

13. McCarty M.F. De novo synthesis of diacylglycerol in endothelium may mediate the association between PAI-1 and the insulin resistance syndrome // Med. Hypotheses. 2005; 64(2): 388-93.

14. Grant P.J. Beneficial effects of metformin on haemostasis and vascular function in man // Diabetes. Metab. 2003 Sep.; 29(4 Pt 2): 6 S. 44-52.

15. Kopp C.W., Kopp H.P., Steiner S., Kriwanek S., Krzyzanowska K., Bartok A., Roka R., Minar E., Schernthaner G. Weight loss reduces tissue factor in morbidly obese patients // Obes. Res. 2003 Aug.; 11(8): 950-6.

16. Folsom A.R., Qamhieh H.T., Wing R.R., Jeffery R.W., Stinson V.L., Kuller L.H., Wu K.K. Impact of weight loss on plasminogen activator inhibitor (PAI-1), factor VII, and other hemostatic factors in moderately overweight adults // Arterioscler. Thromb. 1993 Feb.; 13(2): 162-9.

17. Madsen E.L., Rissanen A., Bruun J.M., Skogstrand K., Tonstad S., Hougaard D.M., Richelsen B. Weight loss larger than 10% is needed for general improvement of levels of circulating adiponectin and markers of inflammation in obese subjects: a 3-year weight loss study // Eur. J. Endocrinol. 2008 Feb.; 158(2): 179-87.

18. Raz O., Rogowski O., Shapira I., Maharshak N., Karni Y., Berliner S. Dissociated effects of physical activity and weight loss on fibrinogen concentrations and markers of red blood cell aggregation. Relevance for life style modification in atherothrombosis // Clin. Hemorheol. Microcirc. 2007; 37(3): 253-62.

19. Hittel D.S., Kraus W.E., Hoffman E.P. Skeletal muscle dictates the fibrinolytic state after exercise training in overweight men with characteristics of metabolic syndrome // J. Physiol. 2003 Apr. 15; 548(Pt. 2): 401-10. 20.

20. Trost S., Pratley R., Sobel B. Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes // Curr. Diab. Rep. 2006 Feb.; 6(1): 47-54.

21. Skurk T., Hauner H. Obesity and impaired fibrinolysis: role of adipose production of plasminogen activator inhibitor-1 // Int. J. Obes. Relat. Metab. Disord. 2004 Nov.; 28(11): 1357-64.

22. Skrha J., Prazny M., Hilgertova J., Kvasnicka J., Kalousova M., Zima T. Oxidative stress and endothelium influenced by metformin in type 2 diabetes mellitus // Eur. J. Clin. Pharmacol. 2007 Dec.; 63(12): 1107-14.

23. Landin K., Tengborn L., Smith U. Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors // J. Intern. Med. 1991 Feb.; 229(2): 181-7.

24. Standeven K.F., Ariлns R.A., Whitaker P., Ashcroft A.E., Weisel J.W., Grant P.J. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation // Diabetes. 2002 Jan.; 51(1): 189-97.

25. Charles M.A., Morange P., Eschwиge E., Andrй P., Vague P., Juhan-Vague I. Effect of weight change and metformin on fibrinolysis and the von Willebrand factor in obese nondiabetic subjects: the BIGPRO1 Study. Biguanides and the Prevention of the Risk of Obesity // Diabetes Care. 1998 Nov.; 21(11): 1967-72.

26. Marfella R., Acampora R., Verrazzo G., Ziccardi P., De Rosa N., Giunta R., Giugliano D. Metformin improves hemodynamic and rheological responses to L-arginine in NIDDM patients // Diabetes Care. 1996 Sep.;19(9): 934-9.

27. Kirpichnikov D., McFarlane S.I., Sowers J.R. Metformin: an update // Ann. Intern. Med. 2002 Jul 2; 137(1): 25-33.

28. Бирюкова Е.В., Гарбузова М.А., Маркина Н.В., Мкртумян А.В. Уникальные эффекты метформина в лечении метаболического синдрома // РМЖ, 07 мая 2009, том 17, №10, С. 692-7.

29. Meaney E., Vela A., Samaniego V., Meaney A., Asbъn J., Zempoalteca J.C., Elisa Z.N., Emma M.N., Guzman M., Hicks J., Ceballos G. Metformin, arterial function, intima-media thickness and nitroxidation in metabolic syndrome: the mefisto study // Clin. Exp. Pharmacol. Physiol. 2008 Aug.; 35(8): 895-903.

30. Bulcao C., Ribeiro-Filho F.F., Saсudo A., Roberta Ferreira S.G. Effects of simvastatin and metformin on inflammation and insulin resistance in individuals with mild metabolic syndrome // Am. J. Cardiovasc. Drugs. 2007; 7(3): 219-24.

31. Isoda K., Young J.L., Zirlik A., MacFarlane L.A., Tsuboi N., Gerdes N., Schцnbeck U., Libby P. Metformin inhibits proinflammatory responses and nuclear factor-kappaB in human vascular wall cells // Arterioscler. Thromb. Vasc. Biol. 2006 Mar.; 26(3): 611-7.

32. Petrazzi L., Grassi D., Polidoro L., D'Aurelio A., Croce G., Properzi G., Tiberti S., Desideri G., Ferri C. Cardiovascular risk and cardiometabolic protection: role of glitazones // J. Nephrol. 2008 Nov.-Dec.; 21(6): 826-35.

33. Yki-Jarvinen H. Thiazolidinediones // N. Engl. J. Med. 2004 Sep. 9; 351(11): 1106-18.

34. Unger R.H. Lipid overload and overflow: metabolic trauma and the metabolic syndrome // Trends. Endocrinol. Metab. 2003 Nov.; 14(9): 398-403.

35. Diamant M., Heine R.J. Thiazolidinediones in type 2 diabetes mellitus: current clinical evidence // Drugs. 2003; 63(13): 1373-405.

36. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifesyill intervention or metformin // N. Engl. J. Med. - 2002; 346, 393-403.

37. Martens F.M., Visseren F.L., Lemay J., de Koning E.J., Rabelink T.J. Metabolic and additional vascular effects of thiazolidinediones // Drugs. 2002; 62(10): 1463-80.

38. Rasouli N., Raue U., Miles L.M., Lu T., Di Gregorio G.B., Elbein S.C., Kern P.A. Pioglitazone improves insulin sensitivity through reduction in muscle lipid and redistribution of lipid into adipose tissue // Am. J. Physiol. Endocrinol. Metab. 2005 May; 288(5): E930-4.

39. Barnett A.H. Redefining the role of thiazolidinediones in the management of type 2 diabetes. //Vasc. Health. Risk. Manag. 2009; 5(1): 141-51. 40. Di Gregorio G.B., Yao-Borengasser A., Rasouli N., Varma V., Lu T., Miles L.M.,

40. Ranganathan G., Peterson C.A., McGehee R.E., Kern P.A. Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone // Diabetes. 2005 Aug.; 54(8): 2305-13.

41. Bodles A.M., Varma V., Yao-Borengasser A., Phanavanh B., Peterson C.A., McGehee R.E. Jr., Rasouli N., Wabitsch M., Kern P.A. Pioglitazone induces apoptosis of macrophages in human adipose tissue // J. Lipid. Res. 2006 Sep.; 47(9): 2080-8.

42. Pasceri V., Wu H.D., Willerson J.T., and Yeh E.T. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators // Circulation 2000; 101: 235-8.

43. Verma S., Wang C.H., Weisel R.D., Badiwala M.V., Li S.H., Fedak P.W., Li R.K., and Mickle D.A. Hyperglycemia potentiates the proatherogenic effects of C-reactive portein: reversal with rosiglitazone // J. Mol. Cell. Cardiol. 2003; 35: 417-9.

44. Nakamura T., Ushiyama C., Shimada N., Hayashi K., Ebihara I., Koide H. Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin- 1 and albumin excretion in diabetes patients // J. Diabetes. Complications. 2000 Sep.-Oct.; 14(5): 250-4.

45. Smith S.A. Central role of the adipocyte in the insulin-sensitising and cardiovascular risk modifying actions of the thiazolidinediones // Biochimie. 2003 Dec.; 85(12): 1219-30.

46. Greenberg A.S. The expanding scope of the metabolic syndrome and implications for the management of cardiovascular risk in type 2 diabetes with particular focus on the emerging role of the thiazolidinediones // J. Diabetes. Complications. 2003 Jul.-Aug.; 17(4): 218-28.

47. Marx N., Sukhova G., Murphy C., Libby P., Plutzky J. Macrophages in human atheroma contain PPARgamma: differentiation-dependent peroxisomal proliferator- activated receptor gamma(PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro // Am. J. Pathol. 1998 Jul; 153(1): 17-23.

48. Maeda N., Takahashi M., Funahashi T., Kihara S., Nishizawa H., Kishida K., Nagaretani H., Matsuda M., Komuro R., Ouchi N., Kuriyama H., Hotta K., Nakamura T., Shimomura I., and Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein // Diabetes. 2001; 50: 2094-9.

49. Yu J.G., Javorschi S., Hevener A.L., Kruszynska Y.T., Norman R.A., Sinha M., and Olefsky J.M. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects // Diabetes. 2002; 51: 2968-74.

50. Derosa G., Gaddi A.V., Piccinni M.N., Ciccarelli L., Salvadeo S., Peros E., Ghelfi M., Ferrari I., Cicero A.F. Antithrombotic effects of rosiglitazone-metformin versus glimepiride-metformin combination therapy in patients with type 2 diabetes mellitus and metabolic syndrome // Pharmacotherapy. 2005 May; 25(5): 637-45.

51. Derosa G., Dangelo A., Ragonesi P.D., Ciccarelli L., Piccinni M.N., Pricolo F., Salvadeo S., Montagna L., Gravina A., Ferrari I., Galli S., Paniga S., Cicero A.F. Effects of rosiglitazone and pioglitazone combined with metformin on the prothrombotic state of patients with type 2 diabetes mellitus and metabolic syndrome // J. Int. Med. Res. 2006 Sep.-Oct.; 34(5): 545-55.

52. Goldstein B.J., Weissman P.N., Wooddell M.J., Waterhouse B.R., Cobitz A.R. Reductions in biomarkers of cardiovascular risk in type 2 diabetes with rosiglitazone added to metformin compared with dose escalation of metformin: an EMPIRE trial sub-study // Curr. Med. Res. Opin. 2006 Sep.;22(9): 1715-23.