Инсулинорезистентность: фокус на патогенез кардиомиопатии

Шишкова В.Н., Мартынов А.И. Инсулинорезистентность: фокус на патогенез кардиомиопатии. Consilium Medicum. 2020; 22 (10): 52–54. DOI: 10.26442/20751753.2020.10.200341

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Shishkova V.N., Martynov A.I. Insulin resistance: focus on the pathogenesis of cardiomyopathy. Consilium Medicum. 2020; 22 (10): 52–54. DOI: 10.26442/20751753.2020.10.200341

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Аннотация

Состояние инсулинорезистентности (ИР) является ключевым звеном патогенеза большого числа болезней, в том числе и сердечно-сосудистых, занимающих лидирующие позиции по показателям заболеваемости и смертности в современном мире. Состояния, объединенные ИР, такие как ожирение, сахарный диабет 2-го типа, артериальная гипертензия и гипертриглицеридемия, составляют патологическую композицию метаболического синдрома. Рост числа пациентов, имеющих метаболический синдром, обусловлен преобладающими в современном мире нездоровым образом жизни и нерациональным питанием, а также частично ассоциирован с тенденцией глобального старения населения большинства развитых стран. В этой связи необходимо подчеркнуть актуальность связи ИР с развитием специфического осложнения – метаболической кардиомиопатии. Учитывая, что в патогенезе данной кардиомиопатии триггерным событием являются нарушение субстратного равновесия и дальнейшее накопление токсических метаболитов липидов в кардиомиоцитах, предложен термин «липотоксическая кардиомиопатия». Развитие данной кардиомиодистрофии связано с появлением гипертрофии и диастолической дисфункции миокарда, в дальнейшем трансформирующихся в хроническую сердечную недостаточность с сохраненной фракцией выброса. Несмотря на то, что связь между развитием липотоксической кардиомиодистрофии и состояниями, ассоциированными с ИР достаточно тесная, до настоящего времени все терапевтические стратегии, основанные только на комплексной терапии с применением антидиабетических и гиполипидемических препаратов, не привели к уменьшению риска развития кардиомиопатии. Существует потребность в поиске эффективных терапевтических стратегий для снижения частоты развития как липотоксической кардиомиодистрофии, так и сопряженной с ней хронической сердечной недостаточности.

Ключевые слова: инсулинорезистентность, кардиомиопатия, хроническая сердечная недостаточность.

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Insulin resistance is the main link of pathogenesis of a lot of diseases, including cardiovascular diseases which are the leading cause of morbidity and mortality worldwide. The combination of insulin resistance – associated disorders, such as obesity, type 2 diabetes mellitus, arterial hypertension and hypertriglyceridemia, refers to metabolic syndrome. The increase in the number of patients with metabolic syndrome is due to a prevalence of unhealthy lifestyle and inappropriate dietary pattern in the modern world, and is also partially associated with the trend of population aging in most developed countries. In this regard, it is necessary to emphasize the relevance of the link between insulin resistance and the development of a specific complication – metabolic cardiomyopathy. Given that the triggering event in pathogenesis of this cardiomyopathy is alterations in substrate balance with following accumulation of lipotoxic metabolites in cardiomyocytes, the term “lipotoxic cardiomyopathy” has been proposed. This cardiomyodystrophy is associated with myocardial hypertrophy and diastolic dysfunction, which thereafter result into chronic heart failure with a preserved ejection fraction. Although the link between the lipotoxic cardiomyodystrophy and insulin resistance–associated disorders is quite close, till now all therapeutic strategies involving only complex therapy with antidiabetic and lipid-lowering drugs have not led to a decrease in the risk for cardiomyopathy. There is a need in searching for effective therapeutic strategies to reduce the incidence of both lipotoxic cardiomyodystrophy and associated chronic heart failure.

Key words: insulin resistance, cardiomyopathy, chronic heart failure.

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17. Ahmad T, Kelly JP, McGarrah RW et al. Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J Am Coll Cardiol 2016; 67: 291–9.
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19. Udell JA, Cavender MA, Bhatt DL et al. Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a metaanalysis of randomised controlled trials. Lancet Diabet Endocrin 2015; 3: 356–66.

________________________________________________

1. Feigin VL, Roth M, Naghavi GA et al. Global burden of stroke and risk factors in 188 countries, during 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet Neurol 2016; 15 (9): 913–24.
2. Chazova I.E., Mychka V.B. Metabolic syndrome. Moscow: Media Medica, 2004 (in Russian).
3. Bozkurt B, Aguilar D, Deswal A, Dunbar SB et al. Contributory risk and management of comorbiditiesof hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure: A scientific statement from the American Heart Association. Circulation 2016; 134 (23): e535–e578.
4. Devereux RB, Roman MJ, Paranicas M. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000; 101: 2271–6.
5. Rubler S. Dlugash J, Yuceoglu YZ et al. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30 (6): 595–602.
6. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of CardiologyFoundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013; 62: e147–e239.
7. Nakamura M, Sadoshima J. Mechanisms of physiological and pathological cardiac hypertrophy. Nat Rev Cardiol 2018; 15: 387–407.
8. Lopaschuk GD, Ussher JR, Folmes CD et al. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010; 90: 207–58.
9. Rijzewijk LJ, van der Meer RW, Diamant M et al. Myoca rdial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008; 52: 1793–9.
10. Rijzewijk LJ, van der Meer RW, Lamb HJ et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 2009; 54: 1524–32.
11. Haemmerle G, Moustafa T, Woelkart G et al. ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-a and PGC-1. Nat Med 2011; 17: 1076–85.
12. Bikman BT, Summers SA. Ceramides as modulators of cellular and whole-body metabolism. J Clin Invest 2011; 121: 4222–30.
13. Jornayvaz FR, Shulman GI. Diacylglycerol activation of protein kinase Ce and hepatic insulin resistance. Cell Metab 2012; 15: 574–84.
14. McCoin CS, Knotss TA, Adams SH. Acylcarnitines – old actors auditioning for new roles in metabolic physiology. Nat Rev Endocrinol 2015; 11: 617–25.
15. Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance. Diabetes 2013; 62: 1–8.
16. Makrecka M, Kuka J, Volska K et al. Long-chain acylcarnitine content determines the pattern of energymetabolism in cardiac mitochondria. Mol Cell Biochem 2014; 395: 1–10.
17. Ahmad T, Kelly JP, McGarrah RW et al. Prognostic implications of long-chain acylcarnitines in heart failure and reversibility with mechanical circulatory support. J Am Coll Cardiol 2016; 67: 291–9.
18. Bray GA, Frunbeck G, Ryan DH et al. Management of obesity. Lancet 2016; 387: 1947–56.
19. Udell JA, Cavender MA, Bhatt DL et al. Glucose-lowering drugs or strategies and cardiovascular outcomes in patients with or at risk for type 2 diabetes: a metaanalysis of randomised controlled trials. Lancet Diabet Endocrin 2015; 3: 356–66.

Авторы

В.Н. Шишкова*1,2, А.И. Мартынов2

1 ГБУЗ «Центр патологии речи и нейрореабилитации» Департамента здравоохранения г. Москвы, Москва, Россия;
2 ФГБОУ ВО «Московский государственный медико-стоматологический университет им. А.И. Евдокимова» Минздрава России, Москва, Россия
*veronika-1306@mail.ru

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Veronika N. Shishkova*1,2, Anatolii I. Martynov2

1 Center for Speech Pathology and Neurorehabilitation, Moscow, Russia;
2 Yevdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
*veronika-1306@mail.ru

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