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Diabetic cardiomyopathy, causes and effects

Abstract

Diabetes is associated with increased incidence of heart failure even after controlling for coronary artery disease and hypertension. Thus, as diabetic cardiomyopathy has become an increasingly recognized entity among clinicians, a better understanding of its pathophysiology is necessary for early diagnosis and the development of treatment strategies for diabetes-associated cardiovascular dysfunction. We will review recent basic and clinical research into the manifestations and the pathophysiological mechanisms of diabetic cardiomyopathy. The discussion will be focused on the structural, functional and metabolic changes that occur in the myocardium in diabetes and how these changes may contribute to the development of diabetic cardiomyopathy in affected humans and relevant animal models.

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References

  1. 1.

    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(6):595–602.

  2. 2.

    Hayat SA, Patel B, Khattar RS, Malik RA. Diabetic cardiomyopathy: mechanisms, diagnosis and treatment. Clin Sci (Lond) 2004;107(6):539–57.

  3. 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(9):748–57.

  4. 4.

    Galderisi M, Anderson KM, Wilson PW, Levy D. Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol. 1991;68(1):85–9.

  5. 5.

    Devereux RB, Roman MJ, Paranicas M, O’Grady MJ, Lee ET, Welty TK, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000;101(19):2271–6.

  6. 6.

    Eguchi K, Boden-Albala B, Jin Z, Rundek T, Sacco RL, Homma S, et al. Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population. Am J Cardiol. 2008;101(12):1787–91.

  7. 7.

    Rerkpattanapipat P, D’Agostino Jr RB, Link KM, Shahar E, Lima JA, Bluemke DA, et al. Location of arterial stiffening differs in those with impaired fasting glucose versus diabetes: implications for left ventricular hypertrophy from the Multi-Ethnic Study of Atherosclerosis. Diabetes 2009;58(4):946–53.

  8. 8.

    Woodiwiss AJ, Libhaber CD, Majane OH, Libhaber E, Maseko M, Norton GR. Obesity promotes left ventricular concentric rather than eccentric geometric remodeling and hypertrophy independent of blood pressure. Am J Hypertens. 2008;21(10):1144–51.

  9. 9.

    Barouch LA, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 2003;108(6):754–9.

  10. 10.

    Xu FP, Chen MS, Wang YZ, Yi Q, Lin SB, Chen AF, et al. Leptin induces hypertrophy via endothelin-1-reactive oxygen species pathway in cultured neonatal rat cardiomyocytes. Circulation 2004;110(10):1269–75.

  11. 11.

    Kim M, Oh JK, Sakata S, Liang I, Park W, Hajjar RJ, et al. Role of resistin in cardiac contractility and hypertrophy. J Mol Cell Cardiol. 2008;45(2):270–80.

  12. 12.

    Bahrami H, Bluemke DA, Kronmal R, Bertoni AG, Lloyd-Jones DM, Shahar E, et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity: the MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol. 2008;51(18):1775–83.

  13. 13.

    Karason K, Sjostrom L, Wallentin I, Peltonen M. Impact of blood pressure and insulin on the relationship between body fat and left ventricular structure. Eur Heart J. 2003;24(16):1500–5.

  14. 14.

    Ingelsson E, Sundstrom J, Arnlov J, Zethelius B, Lind L. Insulin resistance and risk of congestive heart failure. Jama 2005;294(3):334–41.

  15. 15.

    Cook SA, Varela-Carver A, Mongillo M, Kleinert C, Khan MT, Leccisotti L, Strickland N, Matsui T, Das S, Rosenzweig A et al: Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. Eur Heart J. 2009.

  16. 16.

    Belke DD, Betuing S, Tuttle MJ, Graveleau C, Young ME, Pham M, et al. Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Invest. 2002;109(5):629–39.

  17. 17.

    Wende AR, Abel ED: Lipotoxicity in the heart. Biochim Biophys Acta 2009.

  18. 18.

    Regan TJ, Lyons MM, Ahmed SS, Levinson GE, Oldewurtel HA, Ahmad MR, et al. Evidence for cardiomyopathy in familial diabetes mellitus. J Clin Invest. 1977;60(4):884–99.

  19. 19.

    Sharma S, Adrogue JV, Golfman L, Uray I, Lemm J, Youker K, et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. Faseb J. 2004;18(14):1692–700.

  20. 20.

    McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007;116(10):1170–5.

  21. 21.

    Rijzewijk LJ, van der Meer RW, Smit JW, Diamant M, Bax JJ, Hammer S, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol. 2008;52(22):1793–9.

  22. 22.

    van der Meer RW, Rijzewijk LJ, de Jong HW, Lamb HJ, Lubberink M, Romijn JA, et al. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 2009;119(15):2069–77.

  23. 23.

    Abel ED, Litwin SE, Sweeney G. Cardiac remodeling in obesity. Physiol Rev. 2008;88(2):389–419.

  24. 24.

    Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007;115(25):3213–23.

  25. 25.

    Chiu HC, Kovacs A, Ford DA, Hsu FF, Garcia R, Herrero P, et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest. 2001;107(7):813–22.

  26. 26.

    Yagyu H, Chen G, Yokoyama M, Hirata K, Augustus A, Kako Y, et al. Lipoprotein lipase (LpL) on the surface of cardiomyocytes increases lipid uptake and produces a cardiomyopathy. J Clin Invest. 2003;111(3):419–26.

  27. 27.

    Listenberger LL, Ory DS, Schaffer JE. Palmitate-induced apoptosis can occur through a ceramide-independent pathway. J Biol Chem. 2001;276(18):14890–5.

  28. 28.

    Park TS, Hu Y, Noh HL, Drosatos K, Okajima K, Buchanan J, et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res. 2008;49(10):2101–12.

  29. 29.

    Ostrander DB, Sparagna GC, Amoscato AA, McMillin JB, Dowhan W. Decreased cardiolipin synthesis corresponds with cytochrome c release in palmitate-induced cardiomyocyte apoptosis. J Biol Chem. 2001;276(41):38061–7.

  30. 30.

    Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE. Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res. 2006;47(12):2726–37.

  31. 31.

    Brookheart RT, Michel CI, Listenberger LL, Ory DS, Schaffer JE. The non-coding RNA gadd7 is a regulator of lipid-induced oxidative and endoplasmic reticulum stress. J Biol Chem. 2009;284(12):7446–54.

  32. 32.

    Boudina S, Sena S, Theobald H, Sheng X, Wright JJ, Hu XX, et al. Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 2007;56(10):2457–66.

  33. 33.

    Bugger H, Boudina S, Hu XX, Tuinei J, Zaha VG, Theobald HA, et al. Type 1 diabetic akita mouse hearts are insulin sensitive but manifest structurally abnormal mitochondria that remain coupled despite increased uncoupling protein 3. Diabetes 2008;57(11):2924–32.

  34. 34.

    Boudina S, Bugger H, Sena S, O’Neill BT, Zaha VG, Ilkun O, et al. Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation 2009;119(9):1272–83.

  35. 35.

    Li L, Renier G. Activation of nicotinamide adenine dinucleotide phosphate (reduced form) oxidase by advanced glycation end products links oxidative stress to altered retinal vascular endothelial growth factor expression. Metabolism 2006;55(11):1516–23.

  36. 36.

    Serpillon S, Floyd BC, Gupte RS, George S, Kozicky M, Neito V, et al. Superoxide production by NAD(P)H oxidase and mitochondria is increased in genetically obese and hyperglycemic rat heart and aorta before the development of cardiac dysfunction. The role of glucose-6-phosphate dehydrogenase-derived NADPH. Am J Physiol Heart Circ Physiol. 2009;297(1):H153–62.

  37. 37.

    Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, et al. Myocardial cell death in human diabetes. Circ Res. 2000;87(12):1123–32.

  38. 38.

    Aragno M, Mastrocola R, Medana C, Catalano MG, Vercellinatto I, Danni O, et al. Oxidative stress-dependent impairment of cardiac-specific transcription factors in experimental diabetes. Endocrinology 2006;147(12):5967–74.

  39. 39.

    Chowdhry MF, Vohra HA, Galinanes M. Diabetes increases apoptosis and necrosis in both ischemic and nonischemic human myocardium: role of caspases and poly-adenosine diphosphate-ribose polymerase. J Thorac Cardiovasc Surg. 2007;134(1):124–31. 131 e121–123.

  40. 40.

    Barouch LA, Gao D, Chen L, Miller KL, Xu W, Phan AC, et al. Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesity. Circ Res. 2006;98(1):119–24.

  41. 41.

    Shen E, Li Y, Shan L, Zhu H, Feng Q, Arnold JM, et al. Rac1 is required for cardiomyocyte apoptosis during hyperglycemia. Diabetes 2009;58(10):2386–95.

  42. 42.

    Dhalla NS, Liu X, Panagia V, Takeda N. Subcellular remodeling and heart dysfunction in chronic diabetes. Cardiovasc Res. 1998;40(2):239–47.

  43. 43.

    Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.

  44. 44.

    Symeonides P, Koulouris S, Vratsista E, Triantafyllou K, Ioannidis G, Thalassinos N, et al. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. Eur J Echocardiog. 2007;8(6):480–6.

  45. 45.

    Tsutsui H, Matsushima S, Kinugawa S, Ide T, Inoue N, Ohta Y, et al. Angiotensin II type 1 receptor blocker attenuates myocardial remodeling and preserves diastolic function in diabetic heart. Hypertens Res. 2007;30(5):439–49.

  46. 46.

    Shimizu M, Umeda K, Sugihara N, Yoshio H, Ino H, Takeda R, et al. Collagen remodelling in myocardia of patients with diabetes. J Clin Pathol. 1993;46(1):32–6.

  47. 47.

    Gonzalez-Vilchez F, Ayuela J, Ares M, Pi J, Castillo L, Martin-Duran R. Oxidative stress and fibrosis in incipient myocardial dysfunction in type 2 diabetic patients. Int J Cardiol. 2005;101(1):53–8.

  48. 48.

    Ihm SH, Youn HJ, Shin DI, Jang SW, Park CS, Kim PJ, et al. Serum carboxy-terminal propeptide of type I procollagen (PIP) is a marker of diastolic dysfunction in patients with early type 2 diabetes mellitus. Int J Cardiol. 2007;122(3):e36–8.

  49. 49.

    Mizushige K, Yao L, Noma T, Kiyomoto H, Yu Y, Hosomi N, et al. Alteration in left ventricular diastolic filling and accumulation of myocardial collagen at insulin-resistant prediabetic stage of a type II diabetic rat model. Circulation 2000;101(8):899–907.

  50. 50.

    Ban CR, Twigg SM. Fibrosis in diabetes complications: pathogenic mechanisms and circulating and urinary markers. Vasc Health Risk Manag. 2008;4(3):575–96.

  51. 51.

    Way KJ, Isshiki K, Suzuma K, Yokota T, Zvagelsky D, Schoen FJ, et al. Expression of connective tissue growth factor is increased in injured myocardium associated with protein kinase C beta2 activation and diabetes. Diabetes 2002;51(9):2709–18.

  52. 52.

    McQueen AP, Zhang D, Hu P, Swenson L, Yang Y, Zaha VG, et al. Contractile dysfunction in hypertrophied hearts with deficient insulin receptor signaling: possible role of reduced capillary density. J Mol Cell Cardiol. 2005;39(6):882–92.

  53. 53.

    Van den Bergh A, Vanderper A, Vangheluwe P, Desjardins F, Nevelsteen I, Verreth W, et al. Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness. Cardiovasc Res. 2008;77(2):371–9.

  54. 54.

    Brooks BA, Franjic B, Ban CR, Swaraj K, Yue DK, Celermajer DS, et al. Diastolic dysfunction and abnormalities of the microcirculation in type 2 diabetes. Diabetes Obes Metab. 2008;10(9):739–46.

  55. 55.

    Shivalkar B, Dhondt D, Goovaerts I, Van Gaal L, Bartunek J, Van Crombrugge P, et al. Flow mediated dilatation and cardiac function in type 1 diabetes mellitus. Am J Cardiol. 2006;97(1):77–82.

  56. 56.

    Ozasa N, Furukawa Y, Morimoto T, Tadamura E, Kita T, Kimura T. Relation among left ventricular mass, insulin resistance, and hemodynamic parameters in type 2 diabetes. Hypertens Res. 2008;31(3):425–32.

  57. 57.

    Hsueh W, Abel ED, Breslow JL, Maeda N, Davis RC, Fisher EA, et al. Recipes for creating animal models of diabetic cardiovascular disease. Circ Res. 2007;100(10):1415–27.

  58. 58.

    Russell JC, Proctor SD. Small animal models of cardiovascular disease: tools for the study of the roles of metabolic syndrome, dyslipidemia, and atherosclerosis. Cardiovasc Pathol. 2006;15(6):318–30.

  59. 59.

    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(3):H976–82.

  60. 60.

    Aasum E, Belke DD, Severson DL, Riemersma RA, Cooper M, Andreassen M, et al. Cardiac function and metabolism in Type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-alpha activator. Am J Physiol Heart Circ Physiol. 2002;283(3):H949–57.

  61. 61.

    Aasum E, Hafstad AD, Severson DL, Larsen TS. Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 2003;52(2):434–41.

  62. 62.

    Christoffersen C, Bollano E, Lindegaard ML, Bartels ED, Goetze JP, Andersen CB, et al. Cardiac lipid accumulation associated with diastolic dysfunction in obese mice. Endocrinology 2003;144(8):3483–90.

  63. 63.

    Dong F, Zhang X, Yang X, Esberg LB, Yang H, Zhang Z, et al. Impaired cardiac contractile function in ventricular myocytes from leptin-deficient ob/ob obese mice. J Endocrinol. 2006;188(1):25–36.

  64. 64.

    Stolen TO, Hoydal MA, Kemi OJ, Catalucci D, Ceci M, Aasum E, et al. Interval training normalizes cardiomyocyte function, diastolic Ca2+ control, and SR Ca2+ release synchronicity in a mouse model of diabetic cardiomyopathy. Circ Res. 2009;105(6):527–36.

  65. 65.

    Fang ZY, Schull-Meade R, Leano R, Mottram PM, Prins JB, Marwick TH. Screening for heart disease in diabetic subjects. Am Heart J. 2005;149(2):349–54.

  66. 66.

    Yu CM, Chau E, Sanderson JE, Fan K, Tang MO, Fung WH, et al. Tissue Doppler echocardiographic evidence of reverse remodeling and improved synchronicity by simultaneously delaying regional contraction after biventricular pacing therapy in heart failure. Circulation 2002;105(4):438–45.

  67. 67.

    Yue P, Arai T, Terashima M, Sheikh AY, Cao F, Charo D, et al. Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse. Am J Physiol Heart Circ Physiol. 2007;292(5):H2106–18.

  68. 68.

    Van den Bergh A, Flameng W, Herijgers P. Type II diabetic mice exhibit contractile dysfunction but maintain cardiac output by favourable loading conditions. Eur J Heart Fail. 2006;8(8):777–83.

  69. 69.

    Radovits T, Korkmaz S, Loganathan S, Barnucz E, Bomicke T, Arif R, et al. Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2009;297(1):H125–33.

  70. 70.

    Scognamiglio R, Avogaro A, Casara D, Crepaldi C, Marin M, Palisi M, et al. Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol. 1998;31(2):404–12.

  71. 71.

    Ha JW, Lee HC, Kang ES, Ahn CM, Kim JM, Ahn JA, et al. Abnormal left ventricular longitudinal functional reserve in patients with diabetes mellitus: implication for detecting subclinical myocardial dysfunction using exercise tissue Doppler echocardiography. Heart 2007;93(12):1571–6.

  72. 72.

    Palmieri V, Capaldo B, Russo C, Iaccarino M, Pezzullo S, Quintavalle G, 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(2):262–8.

  73. 73.

    Abe T, Ohga Y, Tabayashi N, Kobayashi S, Sakata S, Misawa H, et al. Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats. Am J Physiol Heart Circ Physiol. 2002;282(1):H138–48.

  74. 74.

    Boudina S, Sena S, O’Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 2005;112(17):2686–95.

  75. 75.

    Bugger H, Abel ED. Rodent models of diabetic cardiomyopathy. Dis Model Mech. 2009;2(9–10):454–66.

  76. 76.

    Joshi D, Gupta R, Dubey A, Shiwalkar A, Pathak P, Gupta RC, et al. TRC4186, a novel AGE-breaker, improves diabetic cardiomyopathy and nephropathy in Ob-ZSF1 model of type 2 diabetes. J Cardiovasc Pharmacol. 2009;54(1):72–81.

  77. 77.

    Lamounier-Zepter V, Look C, Alvarez J, Christ T, Ravens U, Schunck WH, et al. Adipocyte fatty acid-binding protein suppresses cardiomyocyte contraction: a new link between obesity and heart disease. Circ Res. 2009;105(4):326–34.

  78. 78.

    Bugger H, Abel ED. Molecular mechanisms for myocardial mitochondrial dysfunction in the metabolic syndrome. Clin Sci (Lond) 2008;114(3):195–210.

  79. 79.

    Wright JJ, Kim J, Buchanan J, Boudina S, Sena S, Bakirtzi K, et al. Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding. Cardiovasc Res. 2009;82(2):351–60.

  80. 80.

    Buchanan J, Mazumder PK, Hu P, Chakrabarti G, Roberts MW, Yun UJ, et al. Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 2005;146(12):5341–9.

  81. 81.

    Thai MV, Guruswamy S, Cao KT, Pessin JE, Olson AL. Myocyte enhancer factor 2 (MEF2)-binding site is required for GLUT4 gene expression in transgenic mice. Regulation of MEF2 DNA binding activity in insulin-deficient diabetes. J Biol Chem. 1998;273(23):14285–92.

  82. 82.

    Razeghi P, Young ME, Cockrill TC, Frazier OH, Taegtmeyer H. Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure. Circulation 2002;106(4):407–11.

  83. 83.

    How OJ, Aasum E, Severson DL, Chan WY, Essop MF, Larsen TS. Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes 2006;55(2):466–73.

  84. 84.

    Mazumder PK, O’Neill BT, Roberts MW, Buchanan J, Yun UJ, Cooksey RC, et al. Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 2004;53(9):2366–74.

  85. 85.

    Peterson LR, Herrero P, McGill J, Schechtman KB, Kisrieva-Ware Z, Lesniak D, et al. Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes. Diabetes 2008;57(1):32–40.

  86. 86.

    Peterson LR, Herrero P, Schechtman KB, Racette SB, Waggoner AD, Kisrieva-Ware Z, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109(18):2191–6.

  87. 87.

    Boudina S, Abel ED. Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda) 2006;21:250–8.

  88. 88.

    Bugger H, Chen D, Riehle C, Soto J, Theobald HA, Hu XX, et al. Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita mice. Diabetes 2009;58(9):1986–97.

  89. 89.

    Diamant M, Lamb HJ, Groeneveld Y, Endert EL, Smit JW, Bax JJ, et al. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol. 2003;42(2):328–35.

  90. 90.

    Metzler B, Schocke MF, Steinboeck P, Wolf C, Judmaier W, Lechleitner M, et al. Decreased high-energy phosphate ratios in the myocardium of men with diabetes mellitus type I. J Cardiovasc Magn Reson. 2002;4(4):493–502.

  91. 91.

    Scheuermann-Freestone M, Madsen PL, Manners D, Blamire AM, Buckingham RE, Styles P, et al. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 2003;107(24):3040–6.

  92. 92.

    Rijzewijk LJ, van der Meer RW, Lamb HJ, de Jong HW, Lubberink M, Romijn JA, 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(16):1524–32.

  93. 93.

    Anderson EJ, Kypson AP, Rodriguez E, Anderson CA, Lehr EJ, Neufer PD. Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol. 2009;54(20):1891–8.

  94. 94.

    Hassouna A, Loubani M, Matata BM, Fowler A, Standen NB, Galinanes M. Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium. Cardiovasc Res. 2006;69(2):450–8.

  95. 95.

    Echtay KS, Esteves TC, Pakay JL, Jekabsons MB, Lambert AJ, Portero-Otin M, et al. A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. EMBO J. 2003;22(16):4103–10.

  96. 96.

    Herlein JA, Fink BD, O’Malley Y, Sivitz WI. Superoxide and respiratory coupling in mitochondria of insulin-deficient diabetic rats. Endocrinology 2009;150(1):46–55.

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Acknowledgments

Dr. Boudina has been supported by the JDRF, and is currently supported by NIH P30 HL101310 and a Scientist Development Award from the American Heart Association. Dr. Abel is an Established Investigator of the American Heart Association and is supported by the American Diabetes Association and UO1 HL087947 (Animal Models of Diabetes Complications Consortium).

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Correspondence to Evan Dale Abel.

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Boudina, S., Abel, E.D. Diabetic cardiomyopathy, causes and effects. Rev Endocr Metab Disord 11, 31–39 (2010) doi:10.1007/s11154-010-9131-7

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Keywords

  • Diabetic cardiomyopathy
  • Diastolic dysfunction
  • Substrate utilization
  • Mitochondrial dysfunction
  • Uncoupling