A comprehensive approach to type 2 diabetes mellitus – way to reduce mortality from atherosclerosis – associated diseases

The purpose of this review is to inform healthcare professionals that the combination of several risk factors (RF) has a serious effect on the progression of atherosclerosis, the development of cardiovascular (CV) diseases and death in people with type 2 diabetes (T2DM). Each of the factors, as a rule, enhances the effect of the other, and if the patient has several of them, then combining them with diabetes is deadly for him. Only an integrated approach to the treatment and effects on RF can improve the prognosis for patients with type 2 diabetes. It is shown that in the treatment of modern classes of hypoglycemic drugs, complex metabolic control is important. Prevention of CV disease is, therefore, a goal of treatment of T2DM as important as glycemic control. The use of drugs with proven cardiovascular benefits is recommended as part of of glucose-lowering therapy. The data of international studies of preparations of a sodium–glucose co-transporter 2 (SGLT2) inhibitor and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) various links in the pathogenesis of complications of diabetes mellitus (DM) reduce the risk of CV events. Based on the original trial results healthcare professionals should the use of antidiabetic drugs that have been proven to reduce cardiovascular events and mortality.

1. Дедов И.И., Шестакова М.В., Викулова О.К. и др. Сахарный диабет в Российской Федерации: распространенность, заболеваемость, смертность, параметры углеводного обмена и структура сахароснижающей терапии по данным Федерального регистра сахарного диабета, статус 2017 г. // Сах. диабет. 2018. Т. 21, № 3. С. 144–159. doi: 10.14341/DM9686

2. Мустафина С.В., Рымар О.Д., Малютина С.К. и др. Распространенность сахарного диабета у взрослого населения Новосибирска // Сах. диабет. 2017. Т. 20, № 5. С. 329–334. doi: 10.14341/DM8744

3. Мустафина С.В., Овсянникова А.К., Воевода М.И. и др. Распространенность компонентов метаболического синдрома при сахарном диабете 2-го типа и типа MODY у молодых жителей Новосибирска // Терапевт. арх. 2018. Т. 90, № 10. С. 55–59. doi: 10.26442/terarkh2018901055-59

4. Cavender M.A., Steg P.G., Smith S.C., Jr. et al. Impact of diabetes mellitus on hospitalization for heart failure, cardiovascular events, and death: outcomes at 4 years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry // Circulation. 2015. Vol. 132, N 10. P. 923–931. doi: 10.1161/CIRCULATIONAHA.114.014796

5. Алгоритмы специализированной медицинской помощи больным сахарным диабетом / Ред. И.И. Дедов, М.В. Шестаковой, А.Ю. Майорова. 9-й вып. М., 2019. doi: 10.14341/DM221S1

6. Rawshani A., Franzen S., Eliasson B. et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes // N. Engl. J. Med. 2017. Vol. 376, N 15. P. 1407–1418. doi: 10.1056/NEJMoa1608664.

7. Grundy S.M., Benjamin I.J., Burke G.L. et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association // Circulation. 1999. Vol. 100, N 10. P. 1134– 1146. doi: 10.1161/01.cir.100.10.1134

8. Корниенко Е.А., Ойноткинова О.Ш., Баранов А.П. и др. Современные взгляды на этиопатогенез инфаркта миокарда при сахарном диабете 2 типа и методы лечения (обзор литературы) // Вестн. нов. мед. технол. 2015. № 2. Публикация 3-8. URL: http://www.medtsu.tula.ru/VNMT/ Bulletin/E2015-2/5198.pdf. doi: 10.12737/11912

9. Basukala P., Jha B., Yadav B.K., Shrestha P.K. Determination of insulin resistance and beta-cell using homeostatic model assessment in type 2 diabetic patients at diagnosis // J. Diabet. and Metab. 2018. Vol. 9, N 3. ID 790. doi: 10.4172/2155-6156.1000790

10. Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients // BMJ. 2002. Vol. 324. P. 71–86. doi: 10.1136/bmj.324.7329.71

11. Marx N., McGuire D.K., Perkovic V. et al. Composite primary end points in cardiovascular outcomes trials involving type 2 diabetes patients: Should unstable angina be included in the primary end point? // Diabetes Care. 2017. Vol. 40, N 9. P. 1144–1151. doi: 10.2337/dc17-0068

12. Turner R.C., Millns H., Neil H.A. et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23) // BMJ. 1998. Vol. 316, N 7134. P. 823–828. doi: 10.1136/bmj.316.7134.823

13. Hicks K.A., Tcheng J.E., Bozkurt B. et al. 2014 ACC/AHA key data elements and definitions for cardiovascular endpoint events in clinical trials: A report of the American College of Cardiology / American Heart Association Task Force on Clinical Data Standards (Writing Committee to develop Cardiovascular Endpoints Data Standards) // J. Am. Coll. Cardiol. 2015. Vol. 66, N 4. P. 403–469. doi: 10.1016/j.jacc.2014.12.018

14. Peterson S., Peto V., Rayner M. et al. European cardiovascular disease statistics. 2-nd ed. London: British Heart Foundation, 2005. P. 17–24.

15. Fox C.S., Sullivan L., D'Agostino R.B., Sr., Wilson P.W. The significant effect of diabetes duration on coronary heart disease mortality: the Framingham Heart Study // Diabetes Care. 2004. Vol. 27, N 3. P. 704–708. doi: 10.2337/diacare.27.3.704

16. Levitzky Y.S., Pencina M.J., D'Agostino R.B. et al. Impact of impaired fasting glucose on cardiovascular disease: the Framingham Heart Study // J. Am. Coll. Cardiol. 2008. Vol. 51, N 3. P. 264–270. doi: 10.1016/j.jacc.2007.09.038

17. Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement // Ann. Intern. Med. 2009. Vol. 150, N 6. P. 396–404. doi: 10.7326/0003-4819-150-6-20090317000008

18. Kavaric N., Klisic A., Ninic A. Cardiovascular risk estimated by UKPDS risk engine algorithm in diabetes // Open Med. (Wars.). 2018. Vol. 13. P. 610–617. doi: 10.1515/med-2018-0086

19. Zinman B., Wanner C., Lachin J.M. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes // N. Engl. J. Med. 2015. Vol. 373, N 22. P. 2117–2128. doi: 10.1056/NEJMoa1504720

20. Sattar N., McLaren J., Kristensen S.L. et al. SGLT2 Inhibition and cardiovascular events: why did EMPAREG Outcomes surprise and what were the likely mechanisms? // Diabetologia. 2016. Vol. 59, N 7. P. 1333–1339. doi: 10.1007/s00125-016-3956-x

21. Basile J.N. The potential of sodium glucose cotransporter 2 (SGLT2) inhibitors to reduce cardiovascular risk in patients with type 2 diabetes (T2DM) // J. Diabet. Complicat. 2013. Vol. 27, N 3. P. 280–286. doi: 10.1016/j.jdiacomp.2012.12.004

22. Ferrannini E., Mark M., Mayoux E. CV Protection in the EMPA-REG OUTCOME trial: A «thrifty substrate» hypothesis // Diabetes Care. 2016. Vol. 39, N 7. P. 1108–1114. doi: 10.2337/dc16-0330

23. Mc Murray J. EMPA-REG the «diuretic hypothesis» // J. Diabet. Complicat. 2016. Vol. 30. P. 3–4. doi: 10.1016/j.jdiacomp.2015.10.012

24. De Fronzo R.A. The EMPA-REG study: what has it told us? A diabetologist’s perspective // J. Diabetes Complications. 2016. Vol. 30. P. 1–2. doi: 10.1016/j.jdiacomp.2015.10.013

25. Cherney D.Z., Perkins B.A., Soleymanlou N. et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus // Circulation. 2014. Vol. 129, N 5. P. 587– 597. doi: 10.1161/CIRCULATIONAHA.113.005081

26. Ferrannini E., Baldi S., Frascerra S. et al. Shift to fatty substrates utilization in response to sodium-glucose co-transporter-2 inhibition in nondiabetic subjects and type 2 diabetic patients // Diabetes. 2016. Vol. 65, N 5. P. 1190–1195. doi: 10.2337/db15-1356

27. Baartscheer A., Schumacher C.A., Wust R.C. et al. Empagliflozin decreases myocardial cytoplasmic Na+ through inhibition of the cardiac Na+/H+ exchanger in rats and rabbits // Diabetologia. 2017. Vol. 60, N 3. P. 568–573. doi: 10.1007/s00125-016-4134-x

28. Bode B., Stenlof K., Sullivan D. et al. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: a randomized trial // Hosp. Pract. (1995). 2013. Vol. 41, N 2. P. 72–84. doi: 10.3810/hp.2013.04.1020

29. Ashrafian H., Frenneaux M.P., Opie L.H. Metabolic mechanisms in heart failure // Circulation. 2007. Vol. 116, N 4. P. 434–448. doi: 10.1161/CIRCULATIONAHA.107.702795

30. Neal B., Perkovic V., Mahaffey K.W. et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes // N. Engl. J. Med. 2017. Vol. 377, N 7. P. 644–657. doi: 10.1056/NEJMoa1611925

31. Radholm K., Figtree G., Perkovic V. et al. Canagliflozin and heart failure in type 2 diabetes mellitus: results from the CANVAS Program (Canagliflozin Cardiovascular Assessment Study) // Circulation. 2018. Vol. 138. P. 458–468. doi: 10.1161/CIRCULATIONAHA. 118.034222

32. Wiviott S.D., Raz I., Bonaca M.P. et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes // N. Engl. J. Med. 2019. Vol. 380, N 4. P. 347–357. doi: 10.1056/NEJMoa1812389

33. Pfeffer M.A., Claggett B., Diaz R. et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome // N. Engl. J. Med. 2015. Vol. 373, N 23. P. 2247–2257. doi: 10.1056/NEJMoa1509225

34. Marso S.P., Daniels G.H., Brown-Frandsen K. et al. Liraglutide and cardiovascular outcomes in type 2 diabetes // N. Engl. J. Med. 2016. Vol. 375. P. 311–322. doi: 10.1056/NEJMoa1603827

35. Marso S.P., Bain S.C., Consoli A. et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes // N. Engl. J. Med. 2016. Vol. 375, N 19. P. 1834–1844. doi: 10.1056/NEJMoa1607141

36. Tamargo J., López-Sendón J. Novel therapeutic targets for the treatment of heart failure // Nat. Rev. Drug Discov 2011. Vol. 10, N 7. P. 536–555. doi: 10.1038/nrd3431

37. Tate M., Chong A., Robinson E. et al. Selective targeting of glucagon-like peptide1 signalling as a novel therapeutic approach for cardiovascular disease in diabetes // Br. J. Pharmacol. 2015. Vol. 172, N 3. P. 721–736. doi: 10.1111/bph.12943

38. Gerstein H.C., Colhoun H.M., Dagenais G.R. et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial // Lancet. 2019. Vol. 394. P. 121–130. doi: 10.1016/S0140-6736(19)31149-3

39. Lim S., Kim K.M., Nauck M.A. Glucagon-like peptide-1 receptor agonists and cardiovascular events: class effects versus individual patterns // Trends Endocrinol. Metab. 2018. Vol. 29. P. 238–248. doi: 10.1016/j.tem.2018.01.011