Korean Circ J.  2015 Jul;45(4):266-272. 10.4070/kcj.2015.45.4.266.

Diabetic Cardiomyopathy; Summary of 41 years

Affiliations
  • 1Turkey Yuksek Ihtisas Education and Research Hospital, Cardiology Clinic, Ankara, Turkey. sametyilmazmd@gmail.com
  • 2Division of Nephrology, University of Texas Health Science Center, San Antonio, TX, USA.

Abstract

Patients with diabetes have an increased risk for development of cardiomyopathy, even in the absence of well known risk factors like coronary artery disease and hypertension. Diabetic cardiomyopathy was first recognized approximately four decades ago. To date, several pathophysiological mechanisms thought to be responsible for this new entity have also been recognized. In the presence of hyperglycemia, non-enzymatic glycosylation of several proteins, reactive oxygen species formation, and fibrosis lead to impairment of cardiac contractile functions. Impaired calcium handling, increased fatty acid oxidation, and increased neurohormonal activation also contribute to this process. Demonstration of left ventricular hypertrophy, early diastolic and late systolic dysfunction by sensitive techniques, help us to diagnose diabetic cardiomyopathy. Traditional treatment of heart failure is beneficial in diabetic cardiomyopathy, but specific strategies for prevention or treatment of cardiac dysfunction in diabetic patients has not been clarified yet. In this review we will discuss clinical and experimental studies focused on pathophysiology of diabetic cardiomyopathy, and summarize diagnostic and therapeutic approaches developed towards this entity.

Keyword

Diabetic cardiomyopathies; Heart failure; Diabetes mellitus

MeSH Terms

Calcium
Cardiomyopathies
Coronary Artery Disease
Diabetes Mellitus
Diabetic Cardiomyopathies*
Fibrosis
Glycosylation
Heart Failure
Humans
Hyperglycemia
Hypertension
Hypertrophy, Left Ventricular
Reactive Oxygen Species
Risk Factors
Calcium
Reactive Oxygen Species

Figure

  • Fig. 1 Pathophysiologic mechanisms of diabetic cardiomyopathy. AGE: advanced glycation end products, TGF-1: transforming growth factor 1, Ca: calcium.


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Reference

1. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA. 2002; 287:2570–2581.
2. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol. 1972; 30:595–602.
3. Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med. 2008; 121:748–757.
4. Maisch B, Alter P, Pankuweit S. Diabetic cardiomyopathy--fact or fiction? Herz. 2011; 36:102–115.
5. From AM, Leibson CL, Bursi F, et al. Diabetes in heart failure: prevalence and impact on outcome in the population. Am J Med. 2006; 119:591–599.
6. Rutter MK, Parise H, Benjamin EJ, et al. Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation. 2003; 107:448–454.
7. Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation. 2000; 101:2271–2276.
8. Velagaleti RS, Gona P, Chuang ML, et al. Relations of insulin resistance and glycemic abnormalities to cardiovascular magnetic resonance measures of cardiac structure and function: the Framingham Heart Study. Circ Cardiovasc Imaging. 2010; 3:257–263.
9. Palmieri V, Capaldo B, Russo C, et al. Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: insights from echocardiography and exercise cardiac performance evaluation. Diabetes Res Clin Pract. 2008; 79:262–268.
10. Huisamen B, van Zyl M, Keyser A, Lochner A. The effects of insulin and beta-adrenergic stimulation on glucose transport, glut 4 and PKB activation in the myocardium of lean and obese non-insulin dependent diabetes mellitus rats. Mol Cell Biochem. 2001; 223:15–25.
11. Cay S, Ozturk S, Biyikoglu SF, Atak R, Balbay Y, Aydogdu S. Association of aortic pressures with fasting plasma glucose in patients with and without impaired fasting glucose. Blood Press. 2008; 17:164–169.
12. Paulus WJ, Tschöpe C, Sanderson JE, et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J. 2007; 28:2539–2550.
13. Brooks BA, Franjic B, Ban CR, et al. Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes. Diabetes Obes Metab. 2008; 10:739–746.
14. Shivalkar B, Dhondt D, Goovaerts I, et al. Flow mediated dilatation and cardiac function in type 1 diabetes mellitus. Am J Cardiol. 2006; 97:77–82.
15. Adal E, Koyuncu G, Aydin A, Celebi A, Kavunoğlu G, Cam H. Asymptomatic cardiomyopathy in children and adolescents with type 1 diabetes mellitus: association of echocardiographic indicators with duration of diabetes mellitus and metabolic parameters. J Pediatr Endocrinol Metab. 2006; 19:713–726.
16. von Bibra H, St John Sutton M. Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis. Diabetologia. 2010; 53:1033–1045.
17. Di Bonito P, Moio N, Cavuto L, et al. Early detection of diabetic cardiomyopathy: usefulness of tissue Doppler imaging. Diabet Med. 2005; 22:1720–1725.
18. Semeniuk LM, Kryski AJ, Severson DL. Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice. Am J Physiol Heart Circ Physiol. 2002; 283:H976–H982.
19. Bella JN, Devereux RB, Roman MJ, et al. Separate and joint effects of systemic hypertension and diabetes mellitus on left ventricular structure and function in American Indians (the Strong Heart Study). Am J Cardiol. 2001; 87:1260–1265.
20. Jellis CL, Stanton T, Leano R, Martin J, Marwick TH. Usefulness of at rest and exercise hemodynamics to detect subclinical myocardial disease in type 2 diabetes mellitus. Am J Cardiol. 2011; 107:615–621.
21. Christoffersen C, Bollano E, Lindegaard ML, et al. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology. 2003; 144:3483–3490.
22. Pereira L, Matthes J, Schuster I, et al. Mechanisms of [Ca2+]i transient decrease in cardiomyopathy of db/db type 2 diabetic mice. Diabetes. 2006; 55:608–615.
23. Shishehbor MH, Hoogwerf BJ, Schoenhagen P, et al. Relation of hemoglobin A1c to left ventricular relaxation in patients with type 1 diabetes mellitus and without overt heart disease. Am J Cardiol. 2003; 91:1514–1517.
24. Malhotra A, Sanghi V. Regulation of contractile proteins in diabetic heart. Cardiovasc Res. 1997; 34:34–40.
25. Jweied EE, McKinney RD, Walker LA, et al. Depressed cardiac myofilament function in human diabetes mellitus. Am J Physiol Heart Circ Physiol. 2005; 289:H2478–H2483.
26. Falcão-Pires I, Palladini G, Gonçalves N, et al. Distinct mechanisms for diastolic dysfunction in diabetes mellitus and chronic pressure-overload. Basic Res Cardiol. 2011; 106:801–814.
27. Rijzewijk LJ, van der Meer RW, Smit JW, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008; 52:1793–1799.
28. Amin AH, El-Missiry MA, Othman AI. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis. Eur J Pharmacol. 2015; 747:166–173.
29. Seddon M, Looi YH, Shah AM. Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart. 2007; 93:903–907.
30. Turko IV, Li L, Aulak KS, Stuehr DJ, Chang YJ, Murad F. Protein tyrosine nitration in the mitochondria from diabetic mouse heart. Implications to dysfunctional mitochondria in diabetes. J Biol Chem. 2003; 278:33972–33977.
31. Cai L, Wang J, Li Y, et al. Inhibition of superoxide generation and associated nitrosative damage is involved in metallothionein prevention of diabetic cardiomyopathy. Diabetes. 2005; 54:1829–1837.
32. Maalouf RM, Eid AA, Gorin YC, et al. Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes. Am J Physiol Cell Physiol. 2012; 302:C597–C604.
33. Shen X, Zheng S, Metreveli NS, Epstein PN. Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes. 2006; 55:798–805.
34. Thomas CM, Yong QC, Rosa RM, et al. Cardiac-specific suppression of NF-κB signaling prevents diabetic cardiomyopathy via inhibition of the renin-angiotensin system. Am J Physiol Heart Circ Physiol. 2014; 307:H1036–H1045.
35. Feliers D, Gorin Y, Ghosh-Choudhury G, Abboud HE, Kasinath BS. Angiotensin II stimulation of VEGF mRNA translation requires production of reactive oxygen species. Am J Physiol Renal Physiol. 2006; 290:F927–F936.
36. Rosenkranz S. TGF-beta1 and angiotensin networking in cardiac remodeling. Cardiovasc Res. 2004; 63:423–432.
37. Berg TJ, Snorgaard O, Faber J, et al. Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes. Diabetes Care. 1999; 22:1186–1190.
38. Yoshida N, Okumura K, Aso Y. High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes. Metabolism. 2005; 54:345–350.
39. Lapolla A, Piarulli F, Sartore G, et al. Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease. Diabetes Care. 2007; 30:670–676.
40. Nożyński J, Zakliczyński M, Konecka-Mrówka D, et al. Advanced glycation end-products in myocardium-supported vessels: effects of heart failure and diabetes mellitus. J Heart Lung Transplant. 2011; 30:558–564.
41. Nielsen JM, Kristiansen SB, Nørregaard R. et al. Blockage of receptor for advanced glycation end products prevents development of cardiac dysfunction in db/db type 2 diabetic mice. Eur J Heart Fail. 2009; 11:638–647.
42. Wu MS, Liang JT, Lin YD, Wu ET, Tseng YZ, Chang KC. Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes. Br J Pharmacol. 2008; 154:758–764.
43. Schalkwijk CG, Stehouwer CD. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci. 2005; 109:143–159.
44. Frank PG, Lisanti MP. ICAM-1: role in inflammation and in the regulation of vascular permeability. Am J Physiol Heart Circ Physiol. 2008; 295:H926–H927.
45. Dobrin JS, Lebeche D. Diabetic cardiomyopathy: signaling defects and therapeutic approaches. Expert Rev Cardiovasc Ther. 2010; 8:373–391.
46. Bugger H, Abel ED. Mitochondria in the diabetic heart. Cardiovasc Res. 2010; 88:229–240.
47. Kiencke S, Handschin R, von Dahlen R, et al. Pre-clinical diabetic cardiomyopathy: prevalence, screening, and outcome. Eur J Heart Fail. 2010; 12:951–957.
48. von Bibra H, Hansen A, Dounis V, Bystedt T, Malmberg K, Rydén L. Augmented metabolic control improves myocardial diastolic function and perfusion in patients with non-insulin dependent diabetes. Heart. 2004; 90:1483–1484.
49. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009; 373:1765–1772.
50. He YM, Yang XJ, Zhao X, et al. β-Blockers in heart failure: benefits of β-blockers according to varying male proportions of study patients. Clin Cardiol. 2012; 35:505–511.
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