Комплексное понимание рисков инсульта и его прогноза при сахарном диабете 2 типа. Есть ли профилактическая стратегия?

Инсульт – серьезное и инвалидизирующее заболевание с высокой смертностью, которое становится все более распространенным в мире, создавая серьезную угрозу здоровью и качеству жизни пациентов. Особую роль в увеличении риска инсульта играет сахарный диабет 2 типа, который не только увеличивает вероятность развития инсульта, но также негативно влияет на исход и возможность повторных инсультов.

С целью предотвращения инсульта необходима систематическая профилактика, включая коррекцию факторов риска и использование эффективных лекарственных средств. Одним из таких препаратов является пиоглитазон. Многие исследования подтверждают его эффективность в снижении вероятности сердечно-сосудистых событий, включая инсульт, как для вторичной, так и для первичной профилактики.

Пиоглитазон может оказаться особенно полезным для пациентов с высоким риском сердечно-сосудистых заболеваний и тем, у кого в анамнезе имеется ишемическое поражение головного мозга. Несмотря на известные побочные эффекты, его преимущества в профилактике инсульта превышают возможные недостатки.

Данный обзор предоставляет важные аспекты роли сахарного диабета 2 типа в увеличении риска инсульта и обсуждает перспективы использования пиоглитазона в качестве лекарственной терапии, влияющей на риски инсульта и его прогноз.

1. Sun H, Saeedi P, Karuranga S, et al. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:109119. doi:10.1016/j.diabres.2021.109119

2. Emerging Risk Factors Collaboration, Sarwar N, Gao P, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet. 2010;375:2215–2222

3. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:3227–3337.

4. Sun Y, Toh MP. Impact of diabetes mellitus (DM) on the health-care utilization and clinical outcomes of patients with stroke in Singapore. Value Health 2009;12 Suppl 3: S101-S105.

5. Folsom AR, Rasmussen ML, Chambless LE, et al. Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. Diabetes Care. 1999;22:1077–1083.

6. Krinock MJ, Singhal NS. Diabetes, stroke, and neuroresilience: looking beyond hyperglycemia. Ann N Y Acad Sci. 2021;1495(1):78–98. doi:10.1111/nyas.14583

7. Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008;168:2070–2080.

8. Rawshani A, Rawshani A, Franzén S, et al. Risk factors, mortality, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2018; 379: 633–644.

9. Zabala A, Darsalia V, Holzmann MJ, et al. Risk of first stroke in people with type 2 diabetes and its relation to glycaemic control: a nationwide observational study. Diabetes Obes Metab. 2020; 22: 182–190.

10. Zhao, M., Song, L., Sun, L., Wang, M., Wang, C., Yao, S., Li, Y., Yun, C., Zhang, S., Sun, Y., Hou, Z., Wu, S., & Xue, H. (2021). Associations of Type 2 Diabetes Onset Age With Cardiovascular Disease and Mortality: The Kailuan Study. Diabetes care, 44(6), 1426–1432. https://doi.org/10.2337/dc20–2375

11. Li Zhang, Xianqi Li, Charles D. A. Wolfe, Matthew D. L. O’Connell, Yanzhong Wang; Diabetes As an Independent Risk Factor for Stroke Recurrence in Ischemic Stroke Patients: An Updated Meta-Analysis. Neuroepidemiology 9 December 2021; 55 (6): 427–435.

12. Zhang, Y., Jin, A., Meng, X., Wang, M., Li, H., Pan, Y., & Wang, Y. (2022). Association between diabetes duration and 1-year prognosis of stroke: A national registry study. Brain and behavior, 12(9), e2725. https://doi.org/10.1002/brb3.2725

13. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56:1113–1132.

14. Mitsios JP, Ekinci EI, Mitsios GP, Churilov L, Thijs V. Relationship between glycated hemoglobin and stroke risk: a systematic review and meta-analysis. J Am Heart Assoc. 2018;7(11). pii): e007858. https://doi.org/10.1161/JAHA.117.007858.

15. Kosiborod M, Gomes MB, Nicolucci A, et al. Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program). Cardiovasc Diabetol. 2018;17:150.

16. Kelly, T. N. (2009). Systematic Review: Glucose Control and Cardiovascular Disease in Type 2 Diabetes. Annals of Internal Medicine, 151(6), 394. doi:10.7326/0003-4819-151-6-200909150-00137

17. Ma ZY, Wu YY, Cui HY, Yao GY, Bian H. Factors Influencing Post-Stroke Cognitive Impairment in Patients with Type 2 Diabetes Mellitus. Clin Interv Aging. 2022;17:653–664. Published 2022 Apr 29. doi:10.2147/CIA.S355242

18. Tsivgoulis G, Katsanos AH, Mavridis D, et al. Association of baseline hyperglycemia with outcomes of patients with and without diabetes with acute ischemic stroke treated with intravenous thrombolysis: a propensity score-matched analysis from the SITS-ISTR registry. Diabetes. 2019; 68: 1861–1869.

19. Johnston KC, Bruno A, Pauls Q, et al. Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke: the SHINE randomized clinical trial. JAMA. 2019; 326: 326–335.

20. Zhang C, Zhou YH, Xu CL, Chi FL, Ju HN. Efficacy of intensive control of glucose in stroke prevention: a meta-analysis of data from 59,197 participants in 9 randomized controlled trials. PLoS One. 2013; 8: e54465.

21. Bellolio MF, Gilmore RM, Ganti L. Insulin for glycaemic control in acute ischaemic stroke. Cochrane Database Syst Rev. 2014; CD005346.

22. Zheng C, Zhao X. Intensive versus standard glucose control in patients with ischemic stroke: a meta-analysis of randomized controlled trials. World Neurosurg. 2020; 136: e487-e495.

23. Dormandy JA, Charbonnel B, Eckland DJ, et al.; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366:1279–1289.

24. Lebovitz HE, Banerji MA. Insulin resistance and its treatment by thiazolidinediones. Recent Prog Horm Res. 2001;56:265–294.

25. DeFronzo RA, Inzucchi S, Abdul-Ghani M, Nissen SE. Pioglitazone: The forgotten, cost-effective cardioprotective drug for type 2 diabetes. Diabetes and Vascular Disease Research. 2019;16(2):133–143. doi:10.1177/1479164118825376

26. Liu J, Wang LN. Peroxisome proliferator-activated receptor gamma agonists for preventing recurrent stroke and other vascular events in patients with stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2015; CD010693. 29;(10).

27. Yaghi S, Furie KL, Viscoli CM, et al. Pioglitazone prevents stroke in patients with a recent transient ischemic attack or ischemic stroke: a planned secondary analysis of the IRIS trial (insulin resistance intervention after stroke). Circulation 2018; 137: 455–463.

28. Tzoulaki I, Molokhia M, Curcin V, et al. Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database. BMJ 2009; 339: b4731.

29. Morgan CL, Inzucchi SE, Puelles J, Jenkins-Jones S, Currie CJ. Impact of treatment with pioglitazone on stroke outcomes: A real-world database analysis. Diabetes Obes Metab. 2018;20(9):2140–2147. doi:10.1111/dom.13344

30. Vaccaro O, Lucisano G, Masulli M, Bonora E, Del Prato S, Rivellese AA, TOSCA. IT Investigators et al. Cardiovascular effects of pioglitazone or sulfonylureas according to pretreatment risk: moving toward personalized care. J Clin Endocrinol Metab. 2019;104:3296–3302. doi:10.1210/jc.2019-00361.

31. Strongman H, Christopher S, Majak M, et al Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study BMJ Open Diabetes Research and Care 2018;6: e000481. doi:10.1136/bmjdrc-2017-000481

32. Zhou Y, Huang Y, Ji X, Wang X, Shen L, Wang Y. Pioglitazone for the primary and secondary prevention of cardiovascular and renal outcomes in patients with or at high risk of type 2 diabetes mellitus: a meta-analysis. J Clin Endocrinol Metab. 2020 doi:10.1210/clinem/dgz252.

33. Hung YC, Chiu LT, Huang HY, Bau DT. Pioglitazone for primary stroke prevention in Asian patients with type 2 diabetes and cardiovascular risk factors: a retrospective study. Cardiovasc Diabetol. 2020;19(1):94. Published 2020 Jun 20. doi:10.1186/s12933-020-01056-x

34. Ha J, Choi DW, Kim KJ, Kim KY, Nam CM, Kim E. Pioglitazone Use and Reduced Risk of Dementia in Patients With Diabetes Mellitus With a History of Ischemic Stroke. Neurology. 2023;100(17): e1799-e1811. doi:10.1212/WNL.0000000000207069

35. Nesto RW, Bell D, Bonow RO, Fonseca V, Grundy SM, Horton ES, Winter ML, Porte D, Semenkovich CF, Smith S, Young LH, Kahn R. Thiazolidinedione use, fluid retention, and congestive heart failure. A Consensus Statement from the American Heart Association and American Diabetes Association. Circulation. 2003;108:2941–2948.