Bulletin of the Russian Military Medical AcademyBulletin of the Russian Military Medical AcademyВестник Российской военно-медицинской академии1682-73922687-1424Eco-Vector6499510.17816/brmma64995ReviewsОбзорыReview ArticleThe main pathogenetic mechanisms of hypercoagulation in diabetes and the possibility of its drug correctionОсновные патогенетические механизмы гиперкоагуляции при сахарном диабете и возможности ее медикаментозной коррекцииhttps://orcid.org/0000-0002-8396-193657208311867KryukovEvgeny V.КрюковЕвгений Владимирович
Russian Federation

doctor of medical sciences, professor

доктор медицинских наук, профессор

evgeniy.md@mail.ru7787-1364KuchminAlexey N.КучминАлексей Николаевич
Russian Federation

doctor of medical science, professor

доктор медицинских наук, профессор

kuchmin.63@mail.ru2690-3373UmanskayaElena P.УманскаяЕлена Павловна
Russian Federation

candidate of medical sciences

кандидат медицинских наук

elenaumansk@mail.ru1861-8100NagornyMikhail B.НагорныйМихаил Борисович
Russian Federation

candidate of medical sciences

кандидат медицинских наук

ilikedm@mail.ru5766-8003ShevelevAndrey A.ШевелёвАндрей Александрович
Russian Federation

candidate of medical sciences

кандидат медицинских наук

tuostax@mail.ruMilitary Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russian FederationВоенно-медицинская академия имени С.М. Кирова МО РФ150620212321651740904202112042021Copyright ©; 2021, Kryukov E.V., Kuchmin A.N., Umanskaya E.P., Nagorny M.B., Shevelev A.A.Copyright ©; 2021, Крюков Е.В., Кучмин А.Н., Уманская Е.П., Нагорный М.Б., Шевелёв А.А.2021Kryukov E.V., Kuchmin A.N., Umanskaya E.P., Nagorny M.B., Shevelev A.A.Крюков Е.В., Кучмин А.Н., Уманская Е.П., Нагорный М.Б., Шевелёв А.А.http://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/1682-7392/article/view/64995

Disorders in the blood coagulation system play an important role in the development of cardiovascular pathology in diabetes. Factors that cause them are hyperglycemia, insulin deficiency, insulin resistance, dyslipidemia, oxidative stress. The most significant changes are observed in the vascular-platelet link of hemostasis. Diabetes is characterized by morphological and functional changes in the endothelium of blood vessels. The activity of platelets increases, which is manifested by their high level of spontaneous aggregation and increased sensitivity to the action of activating factors. The role in the disturbance of hemostasis is played by increasing the activity of the von Willebrand factor, reflecting damage to endothelial cells. Diabetes is characterized by an increase in the activity of plasma clotting factors (I, II, III, VII, VIII, IX, XI, XII and XIII), activation of the callicrein-kinin system. In some cases, this correlates with the development of complications of diabetes. Characteristic disorders in the coagulation inhibition system are a decrease in the activity of antithrombin III, reduced formation of thrombin-antithrombin complexes, reduction of thrombomodulin and protein C. In diabetes, there is a decrease in fibrinolysis, due to a decrease in the expression of tissue activator plasminogen and an increase in the level of the inhibitor of the activator plasminogen. The possibilities of drug correction of hypercoagulation factors in diabetes are to achieve glycemic control with sugar-reducing drugs and elimination of dyslipidemia through hypolipidemic therapy. The most well-studied sugar-lowering drug that improves the state of the blood clotting system is metformin. The system of hemostasis in diabetic patients is positively affected by statins both due to the direct hypolipidemic effect, and by improving endothelial function and increasing fibrinolysis.

Нарушения в системе коагуляции крови занимают важное место в континууме формирования патологических изменений системы кровообращения при сахарном диабете. Факторы, их обусловливающие, это гипергликемия, дефицит инсулина, инсулинорезистентность, дислипидемия, оксидативный стресс. Наиболее значимые изменения наблюдаются в сосудисто-тромбоцитарном звене гемостаза. Для сахарного диабета характерны морфологические и функциональные изменения в эндотелии сосудов. Увеличивается активность тромбоцитов, что проявляется высоким уровнем их спонтанной агрегации и повышенной чувствительностью к действию активирующих факторов. Роль в нарушении гемостаза играет повышение активности фактора фон Виллебранда, отражающее повреждение эндотелиальных клеток. Для сахарного диабета характерно увеличение активности плазменных факторов свертывания (I, II, III, VII, VIII, IX, XI, XII и XIII), активация калликреин-кининовой системы. В ряде случаев это коррелирует с развитием осложнений сахарного диабета. Наиболее значимыми нарушениями в системе подавления коагуляционных свойств являются уменьшение активности антитромбина III, снижение интенсивности формирования тромбин-антитромбиновых комплексов наряду с уменьшением содержания тромбомодулина и протеина С. При сахарном диабете происходит снижение фибринолиза, обусловленное уменьшением действия тканевого активатора плазминогена наряду с увеличением содержания ингибитора активатора плазминогена. Возможности медикаментозной коррекции гиперкоагуляции при сахарном диабете заключаются в том числе и в достижении гликемического контроля с помощью сахароснижающих средств и устранении дислипидемии путем гиполипидемической терапии. Наиболее хорошо изученным сахароснижающим препаратом, улучшающим состояние свертывающей системы крови, является метформин. На систему гемостаза у больных сахарным диабетом положительно влияют статины как за счет прямого гиполипидемического эффекта, так и за счет улучшения эндотелиальной функции и повышения фибринолиза.

diabetes mellitusplateletsplasma clotting factorsinhibition of coagulationfibrinolysisglycemic controldyslipidemiametforminstatinsсахарный диабеттромбоцитыплазменные факторы свертыванияингибирование коагуляциифибринолизгликемический контрольдислипидемияметформинстатиныDedov II, Shestakova MV, Majorov AJu, editors. Standards of specialized diabetes care. 9th ed. Moscow; 2019. (In Russ.). DOI: 10.14341/DM22151Алгоритмы специализированной медицинской помощи больным сахарным диабетом / под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. Вып. 9. М., 2019. DOI: 10.14341/DM22151Cosentino F, Grant PJ, Aboyans V. 2019 Rekomendacii ESC/EASD po saharnomu diabetu, prediabetu i serdechno-sosudistym zabolevanijam Rabochaja gruppa po saharnomu diabetu, prediabetu i serdechno-sosudistym zabolevanijam Evropejskogo obshhestva kar-diologov (ESC, EOK) i Evropejskoj associacii po izucheniju saharnogo diabeta (EASD, EASD). Rossijskij kardiologicheskij zhurnal. 2020;25(4):101–160. (In Russ.). DOI: 10.15829/1560-4071-2020-3839Cosentino F., Grant P.J., Aboyans V. 2019 Рекомендации ЕSC/EASD по сахарному диабету, предиабету и сердечно-сосудистым заболеваниям Рабочая группа по сахарному диабету, предиабету и сердечно-сосудистым заболеваниям Европейского общества кардиологов (ESC, ЕОК) и Европейской ассоциации по изучению сахарного диабета (EASD, ЕАСД) // Российский кардиологический журнал. 2020. Т. 25, № 4. С. 101–160. DOI: 10.15829/1560-4071-2020-3839Bloomgarden ZT. Cardiovascular disease in diabetes. Diabetes Care. 2010;33(4):e49–54. DOI: 10.2337/dc10-zb04Bloomgarden Z.T. Cardiovascular disease in diabetes // Diabetes Care. 2010. Vol. 33. No. 4. P. e49–54. DOI: 10.2337/dc10-zb04Banga JD, Sixma JJ. Diabetes mellitus, vascular disease and thrombosis. Clin Haematol. 1986;15(2):465–492.Banga J.D., Sixma J.J. Diabetes mellitus, vascular disease and thrombosis // Clin. Haematol. 1986. Vol. 15. No. 2. P. 465–492.Kryukov EV, Panevin TS, Popova LV. Age-related changes in the hemostasis system. Klinicheskaja medicina. 2020;98(1):9–12. (In Russ.).Крюков Е.В., Паневин Т.С., Попова Л.В. Возрастные изменения систем гемостаза // Клиническая медицина. 2020. Т. 98, № 1. С. 9–12.Standeven KF, Ariëns RAS, Whitaker P, et al. The effect of dimethyl biguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002;51(1):189–197. DOI: 10.2337/diabetes.51.1.189Standeven K.F., Ariëns R.A.S., Whitaker P., et al. The effect of dimethyl biguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation // Diabetes. 2002. Vol. 51. No. 1. P. 189–197. DOI: 10.2337/diabetes.51.1.189Tabit CE, Chung WB, Hamburg NM, Vita JA. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev Endocr Metab Disord. 2010;11(1):61–74. DOI: 10.1007/s11154-010-9134-4Tabit C.E., Chung W.B., Hamburg N.M., Vita J.A. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications // Rev. Endocr. Metab. Disord. 2010. Vol. 11. No. 1. P. 61–74. DOI: 10.1007/s11154-010-9134-4Sudic D, Razmara M, Forslund M, et al. High glucose levels enhance platelet activation: involvement of multiple mechanisms. Br J Haematol. 2006;133(3):315–322. DOI: 10.1111/j.1365-2141.2006.06012.xSudic D., Razmara M., Forslund M., et al. High glucose levels enhance platelet activation: involvement of multiple mechanisms // Br. J. Haematol. 2006. Vol. 133. No. 3. P. 315–322. DOI: 10.1111/j.1365-2141.2006.06012.xAmetov AS, Solov’eva OL. Saharnyj diabet 2 tipa. Problemy i reshenija. Moscow: GJeOTAR-Media; 2011. P. 183–210. (In Russ.).Аметов А.С., Соловьева О.Л. Эндотелиальная дисфункция и пути ее коррекции // Сахарный диабет 2 типа. Проблемы и решения. М.: ГЭОТАР-Медиа, 2011. C. 183–210.Barillari G, Fabbro E, Pasca S, Bigotto E. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population. Blood Coagul Fibrinolysis. 2009;20(4):290–296. DOI: 10.1097/MBC.0b013e328329e49bBarillari G., Fabbro E., Pasca S., Bigotto E. Coagulation and oxidative stress plasmatic levels in a type 2 diabetes population // Blood Coagul. Fibrinolysis. 2009. Vol. 20. No. 4. P. 290–296. DOI: 10.1097/MBC.0b013e328329e49bSchneider DJ. Factors contributing to increased platelet reactivity in people with diabetes. Diabetes Care. 2009;32(4):525–527. DOI: 10.2337/dc08-1865Schneider D.J. Factors contributing to increased platelet reactivity in people with diabetes // Diabetes Care. 2009. Vol. 32. No. 4. P. 525–527. DOI: 10.2337/dc08-1865Petrik GG, Pavlishchuk SA, Kosmacheva ED. Diabetes mellitus and cardiovascular complications: focus on hemostasis. Rossijskij kardiologicheskij zhurnal. 2014;(3):114–118. (In Russ.). DOI: 10.15829/1560-4071-2014-3-114-118Петрик Г.Г., Павлищук С.А., Космачева Е.Д. Сахарный диабет и кардиоваскулярные нарушения: фокус на гемостаз // Российский кардиологический журнал. 2014. № 3. С. 114–118. DOI: 10.15829/1560-4071-2014-3-114-118Kearney K, Tomlinson D, Smith K, Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk. Cardiovasc Diabetol. 2017;16(1):34. DOI: 10.1186/s12933-017-0515-9Kearney K., Tomlinson D., Smith K., Ajjan R. Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk // Cardiovasc. Diabetol. 2017. Vol. 16. No. 1. P. 34. DOI: 10.1186/s12933-017-0515-9Sirotkina OV, Zabotina AM, Taraskina AE, et al. Participation of IIb-IIIa glycoprotein in spontaneous platelet aggregation. Bjulleten’ jeksperimental’noj biologii i mediciny. 2007;143(4):398–401. (In Russ.).Сироткина О.В., Заботина А.М., Тараскина А.Е., и др. Участие гликопротеина IIb-IIIa в спонтанной агрегации тромбоцитов // Бюллетень экспериментальной биологии и медицины. 2007. Т. 143, № 4. С. 398–401.Breddin HK, Lippold R, Bittner M, et al. Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG study. Haemostatic parameters as risk factors in healthy volunteers. Atherosclerosis. 1999;144(1):211–219. DOI: 10.1016/s0021-9150(99)00056-8Breddin H.K., Lippold R., Bittner M., et al. Spontaneous platelet aggregation as a predictive risk factor for vascular occlusions in healthy volunteers? Results of the HAPARG study. Haemostatic parameters as risk factors in healthy volunteers // Atherosclerosis. 1999. Vol. 144. No. 1. P. 211–219. DOI: 10.1016/s0021-9150(99)00056-8Shitikova AS. Trombocitarnyj gemostaz. Saint-Peterburg: SPb GMU; 2000. (In Russ.).Шитикова А.С. Тромбоцитарный гемостаз. СПб.: Изд-во СПб ГМУ, 2000.Moroz EV, Artemkin EN, Kryukov EV, Chernetsov VA. Gastro-intestinal tract complications during antithrombotic therapy. Obshhaja reanimatologija. 2018;14(3):15–26. (In Russ.).Мороз Е.В., Артемкин Э.Н., Крюков Е.В., Чернецов В.А. Осложнения со стороны желудочно-кишечного тракта при антитромбической терапии // Общая реаниматология. 2018. Т. 14, № 3. С. 15–26.Sokolov EI, Metelskaya VA, Perova NV. Platelet aggregation, dyslipoproteinemia and polyunsaturated fatty acids. Kardiovaskuljarnaja terapija i profilaktika. 2006;5(5):87–93. (In Russ.).Соколов Е.И., Метельская В.А., Перова Н.В., и др. Взаимосвязь агрегации тромбоцитов с дислипопротеидемиями и полиненасыщенными жирными кислотами // Кардиоваскулярная терапия и профилактика. 2006. Т. 5, № 5. С. 87–93.Frankel DS, Meigs JB, Massaro JM, et al. Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease: the Framingham offspring study. Circulation. 2008;118(24): 2533–2539. DOI: 10.1161/CIRCULATIONAHA.108.792986Frankel D.S., Meigs J.B., Massaro J.M., et al. Von Willebrand factor, type 2 diabetes mellitus, and risk of cardiovascular disease: the Framingham offspring study // Circulation. 2008. Vol. 118. No. 24. P. 2533–2539. DOI: 10.1161/CIRCULATIONAHA.108.792986Novikov VI, Novikov KYu. Antiplatelet therapy use in diabetes mellitus patients: modern approaches and ischemic heart disease prevention perspectives. Consilium Medicum. 2018;20(4):16–23. (In Russ.).Новиков В.И., Новиков К.Ю. Антиагреганты при сахарном диабете: современные подходы и перспективы профилактики ишемической болезни сердца // Consilium Medicum. 2018. Т. 20, № 4. С. 16–23.Folsom AR, Wu KK, Rasmussen M, et al. Determinants of population changes in fibrinogen and factor VII over 6 year: the atherosclerosis risk in communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2000;20(2):601–606. DOI: 10.1161/01.atv.20.2.601Folsom A.R., Wu K.K., Rasmussen M., et al. Determinants of population changes in fibrinogen and factor VII over 6 year: the atherosclerosis risk in communities (ARIC) study // Arterioscler. Thromb. Vasc. Biol. 2000. Vol. 20. No. 2. P. 601–606. DOI: 10.1161/01.atv.20.2.601Corrado E, Rizzo M, Muratori I. Assotiation of elevated fibrinogen and CRP levels with carotid lesions in patients with newly diagnosed hypertension or type 2 diabetes. Arch Med Res. 2006;37(8): 1004–1009. DOI: 10.1016/j.arcmed.2006.06.005Corrado E., Rizzo M., Muratori I. Assotiation of elevated fibrinogen and CRP levels with carotid lesions in patients with newly diagnosed hypertension or type 2 diabetes // Arch. Med. Res. 2006. Vol. 37. No. 8. P. 1004–1009. DOI: 10.1016/j.arcmed.2006.06.005Erem C, Hacihasanoğlu A, Celik S, et al. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications. Med Princ Pract. 2005;14(1):22–30. DOI: 10.1159/000081919Erem C., Hacihasanoğlu A., Celik S., et al. Coagulation and fibrinolysis parameters in type 2 diabetic patients with and without diabetic vascular complications // Med. Princ. Pract. 2005. Vol. 14. No. 1. P. 22–30. DOI: 10.1159/000081919Essing M, Nguyen G, Prié D, et al. 3-hydroxy-3-methylglutaryl coenzyme. A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho proteins. Circ Res. 1998;83(7):683–690. DOI: 10.1161/01.res.83.7.683Essing M., Nguyen G., Prié D., et al. 3-hydroxy-3-methylglutaryl coenzyme. A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells. Role of geranylgeranylation and Rho proteins // Circ. Res. 1998. Vol. 83. No. 7. P. 683–690. DOI: 10.1161/01.res.83.7.683Umpaichitra V, Hussain MM, Castells S. Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolesсents with type 2 diabetes and obesity. Pediatr Res. 2005;58(3):483–487. DOI: 10.1203/01.PDR.0000164307.92308.09Umpaichitra V., Hussain M.M., Castells S. Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolesсents with type 2 diabetes and obesity // Pediatr Res. 2005. Vol. 58. No. 3. P. 483–487. DOI: 10.1203/01.PDR.0000164307.92308.09Gray RP, Panahloo A, Mohamed-Ali V, et al. Proinsulin-like molecules and plasminogen activator inhibitor type 1 (PAI-1) activity in diabetic and non-diabetic subjects with and without myocardial infarction. Atherosclerosis. 1997;130(1–2):171–178. DOI: 10.1016/s0021-9150(96)06070-4Gray R.P., Panahloo A., Mohamed-Ali V., et al. Proinsulin-like molecules and plasminogen activator inhibitor type 1 (PAI-1) activity in diabetic and non-diabetic subjects with and without myocardial infarction // Atherosclerosis. 1997. Vol. 130. No. 1–2. P. 171–178. DOI: 10.1016/s0021-9150(96)06070-4Grant PJ. Beneficial effects of metformin on haemostasis and vascular function in man. Diabetes Metab. 2003;29(4 pt 2): 6S44–6S52. DOI: 10.1016/s1262-3636(03)72787-6Grant P.J. Beneficial effects of metformin on haemostasis and vascular function in man // Diabetes Metab. 2003. Vol. 29. No. 4. Pt. 2. P. 6S44–6S52. DOI: 10.1016/s1262-3636(03)72787-6Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation. 1998;97(12):1129–1135. DOI: 10.1161/01.cir.97.12.1129Laufs U., La Fata V., Plutzky J., Liao J.K. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors // Circulation. 1998. Vol. 97. No. 12. P. 1129–1135. DOI: 10.1161/01.cir.97.12.1129Formoso G, De Filippis EA, Michetti N, et al. Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects. Diabetes Metab Res Rev. 2008;24(3):231–237. DOI: 10.1002/dmrr.794Formoso G., De Filippis E.A., Michetti N., et al. Decreased in vivo oxidative stress and decreased platelet activation following metformin treatment in newly diagnosed type 2 diabetic subjects // Diabetes Metab. Res. Rev. 2008. Vol. 24. No. 3. P. 231–237. DOI: 10.1002/dmrr.794Fanghänel G, Silva U, Sanchez-Reyes L. Effects of metformin on fibrinogen levels in obese patients with type 2 diabetes. Rev Invest Clin. 1998;50(5):389–394.Fanghänel G., Silva U., Sanchez-Reyes L. Effects of metformin on fibrinogen levels in obese patients with type 2 diabetes // Rev. Invest. Clin. 1998. Vol. 50. No. 5. P. 389–394.Anfossi G, Russo I, Bonomo K, Trovati M. The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy. Curr Vasc Pharmacol. 2010;8(3):327–337. DOI: 10.2174/157016110791112359Anfossi G., Russo I., Bonomo K., Trovati M. The cardiovascular effects of metformin: further reasons to consider an old drug as a cornerstone in the therapy // Curr. Vasc. Pharmacol. 2010. Vol. 8. No. 3. P. 327–337. DOI: 10.2174/157016110791112359Gin H, Roudaut MF, Vergnot V, et al. Effect of metformin on fibrinolytic parameters in insulintreated, type 2 diabetic patients. Diabetes Metab. 2003;29(5):505–508. DOI: 10.1016/s1262-3636(07)70064-2Gin H., Roudaut M.F., Vergnot V., et al. Effect of metformin on fibrinolytic parameters in insulintreated, type 2 diabetic patients // Diabetes Metab. 2003. Vol. 29. No. 5. P. 505–508. DOI: 10.1016/s1262-3636(07)70064-2Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups. Diabetes Care. 1993;16(4):621–629. DOI: 10.2337/diacare.16.4.621Nagi D.K., Yudkin J.S. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects. A study of two ethnic groups // Diabetes Care. 1993. Vol. 16. No. 4. P. 621–629. DOI: 10.2337/diacare.16.4.621Janka HU. Platelet and endothelial function tests during metformin treatment in diabetes mellitus (short communication). Horm Metab Res. 1985;15:120–122.Janka H.U. Platelet and endothelial function tests during metformin treatment in diabetes mellitus (short communication) // Horm. Metab. Res. 1985. Vol. 15. P. 120–122.Zadionchenko VS, Shehjan GG, Jalymov AA. Mesto statinov v terapii bol’nyh ishemicheskoj bolezn’ju serdca. Russkij medicinskij zhurnal. 2004;12(9):513. (In Russ.).Задионченко В.С., Шехян Г.Г., Ялымов А.А. Место статинов в терапии больных ишемической болезнью сердца // Русский медицинский журнал. 2004. Т. 12, № 9. C. 513.Oynotkinova OSh, Nikonov EL, Kryukov EV, Baranov AP. Therapeutic aspects of the choice of antithrombotic therapy in patients with multifocal lesions of peripheral arteries. Terapevticheskij arhiv. 2019;91(9):158–164. (In Russ.).Ойноткинова О.Ш., Никонов Е.Л., Крюков Е.В., Баранов А.П. Терапевтические аспекты выбора антитромбической терапии у пациентов с мультифокальным поражением периферических артерий // Терапевтический архив. 2019. Т. 91, № 9. С. 158–164.Severina AS, Shestakova MV. Narushenie sistemy gemostaza u bol’nyh saharnym diabetom. Saharnyj diabet. 2004;(1):62–67. (In Russ.).Северина А.С., Шестакова М.В. Нарушение системы гемостаза у больных сахарным диабетом // Сахарный диабет. 2004. № 1. С. 62–67.Alessi MC, Irène JV. PAI-1 and the metabolic syndrome: the links, causes and consequences. Arterioscler Thromb Vasc Biol. 2006;26(10):2200–2207. DOI: 10.1161/01.ATV.0000242905.41404.68Alessi M.C., Irène J.V. PAI-1 and the metabolic syndrome: the links, causes and consequences // Arterioscler. Thromb. Vasc. Biol. 2006. Vol. 26. No. 10. P. 2200–2207. DOI: 10.1161/01.ATV.0000242905.41404.68Festa A, Williams K, Tracy RP, et al. Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes. Circulation. 2006;113(14):1753–1759. DOI: 10.1161/CIRCULATIONAHA.106.616177Festa A., Williams K., Tracy R.P., et al. Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes // Circulation. 2006;113(14):1753–1759. DOI: 10.1161/CIRCULATIONAHA.106.616177Grant PJ. Metformin reduces circulating factor VII concentrations in patients with type 2 diabetes mellitus. Thromb Hamost. 1998;80(1):209–210.Grant P.J. Metformin reduces circulating factor VII concentrations in patients with type 2 diabetes mellitus // Thromb. Hamost. 1998. Vol. 80. No. 1. P. 209–210.McBane RD, Hardison RM, Sobel BE; Bari 2D Study Group. Comparison of plasminogen activator inhibitor-1, tissue type plasminogen activator antigen, fibrinogen, and D-dimer levels in various age decades in patients with type 2 diabetes mellitus and stable coronary artery disease (from the BARI 2D trial). Am J Cardiol. 2010;105(1):17–24. DOI: 10.1016/j.amjcard.2009.08.643McBane R.D., Hardison R.M., Sobel B.E.; Bari 2D Study Group. Comparison of plasminogen activator inhibitor-1, tissue type plasminogen activator antigen, fibrinogen, and D-dimer levels in various age decades in patients with type 2 diabetes mellitus and stable coronary artery disease (from the BARI 2D trial) // Am. J. Cardiol. 2010. Vol. 105. No. 1. P. 17–24. DOI: 10.1016/j.amjcard.2009.08.643Michelson A. Platelets. Amsterdam, Boston: Academic Press, Elserver Inc; 2007.Michelson A. Platelets. Amsterdam, Boston: Academic Press, Elserver Inc, 2007.Pacher P, Szabó C. Role of poly (ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme. Antioxid Redox Signal. 2005;7(11–12):1568–1580. DOI: 10.1089/ars.2005.7.1568Pacher P., Szabó C. Role of poly (ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: endothelial dysfunction, as a common underlying theme // Antioxid. Redox. Signal. 2005. Vol. 7. No. 11–12. P. 1568–1580. DOI: 10.1089/ars.2005.7.1568Patel A, MacMahon S, Chalmers J, et al; Advance Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358(24):2560-2572. DOI: 10.1056/NEJMoa080298Patel A., MacMahon S., Chalmers J., et al; Advance Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes // N. Engl. J. Med. 2008. Vol. 358. No. 24. P. 2560-2572. DOI: 10.1056/NEJMoa080298Potter van Loon BJ, Kluft C, Radder JK, et al. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin-resistance. Metabolism. 1993;42(8):945–949. DOI: 10.1016/0026-0495(93)90005-9Potter van Loon B.J., Kluft C., Radder J.K., et al. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin-resistance // Metabolism. 1993. Vol. 42. No. 8. P. 945–949. DOI: 10.1016/0026-0495(93)90005-9