Diabetic Cardiovascular Disease: Getting to the Heart of the Matter

  • Linda R. Peterson
  • Clark R. McKenzie
  • Jean E. Schaffer


Diabetes is a major risk factor for heart disease, and heart disease is responsible for substantial morbidity and mortality among people living with diabetes. The diabetic metabolic milieu predisposes to aggressive obstructive coronary artery disease that causes heart attacks, heart failure, and death. Furthermore, diabetes can be associated with heart failure, independent of underlying coronary artery disease, hypertension, or valve abnormalities. The pathogenesis of the vascular and myocardial complications of diabetes is, as yet, incompletely understood. Although a number of medical and surgical approaches can improve outcomes in diabetic patients with cardiovascular disease, much remains to be learned in order to optimize approaches to these critical complications.


Diabetes Coronary artery disease Heart failure 


  1. 1.
    Centers for Disease Control (2011). National Diabetes Fact Sheet. Available from: http://www.cdc.gov/diabetes/pubs/factsheet11.htm.
  2. 2.
    Kannel, W. B., & McGee, D. L. (1979). Diabetes and cardiovascular disease. The Framingham study. JAMA: The Journal of the American Medical Association, 241(19), 2035–2038.CrossRefGoogle Scholar
  3. 3.
    Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). (2001). JAMA, 285(19), 2486–2497.Google Scholar
  4. 4.
    Abbott, R. D., Donahue, R. P., Kannel, W. B., & Wilson, P. W. (1988). The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham study. JAMA: The Journal of the American Medical Association, 260(23), 3456–3460.CrossRefGoogle Scholar
  5. 5.
    Miettinen, H., Lehto, S., Salomaa, V., Mahonen, M., Niemela, M., Haffner, S. M., Pyorala, K., & Tuomilehto, J. (1998). Impact of diabetes on mortality after the first myocardial infarction. The Finmonica Myocardial Infarction Register Study Group. Diabetes Care, 21(1), 69–75.PubMedCrossRefGoogle Scholar
  6. 6.
    Grundy, S. M., Pasternak, R., Greenland, P., Smith, S., Jr., & Fuster, V. (1999). Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the american heart association and the american college of cardiology. Circulation, 100(13), 1481–1492.PubMedCrossRefGoogle Scholar
  7. 7.
    Malmberg, K., Yusuf, S., Gerstein, H. C., Brown, J., Zhao, F., Hunt, D., Piegas, L., Calvin, J., Keltai, M., & Budaj, A. (2000). Impact of diabetes on long-term prognosis in patients with unstable angina and non-q-wave myocardial infarction: results of the oasis (organization to assess strategies for ischemic syndromes) registry. Circulation, 102(9), 1014–1019.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith, J. W., Marcus, F. I., & Serokman, R. (1984). Prognosis of patients with diabetes mellitus after acute myocardial infarction. The American Journal of Cardiology, 54(7), 718–721.PubMedCrossRefGoogle Scholar
  9. 9.
    Stone, P. H., Muller, J. E., Hartwell, T., York, B. J., Rutherford, J. D., Parker, C. B., Turi, Z. G., Strauss, H. W., Willerson, J. T., Robertson, T., et al. (1989). The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The Milis Study Group. Journal of the American College of Cardiology, 14(1), 49–57.PubMedCrossRefGoogle Scholar
  10. 10.
    Mak, K. H., Moliterno, D. J., Granger, C. B., Miller, D. P., White, H. D., Wilcox, R. G., Califf, R. M., & Topol, E. J. (1997). Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries. Journal of the American College of Cardiology, 30(1), 171–179.PubMedCrossRefGoogle Scholar
  11. 11.
    The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. (1996). Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med, 335(4), 217-225.Google Scholar
  12. 12.
    Wingard, D. L., Barrett-Connor, E. L., Scheidt-Nave, C., & McPhillips, J. B. (1993). Prevalence of cardiovascular and renal complications in older adults with normal or impaired glucose tolerance or niddm. A population-based study. Diabetes Care, 16(7), 1022–1025.PubMedCrossRefGoogle Scholar
  13. 13.
    Goldberg, I. J. (2001). Clinical review 124: Diabetic dyslipidemia: causes and consequences. Journal of Clinical Endocrinology and Metabolism, 86(3), 965–971.PubMedCrossRefGoogle Scholar
  14. 14.
    Ginsberg, H. N. (1996). Diabetic dyslipidemia: basic mechanisms underlying the common hypertriglyceridemia and low hdl cholesterol levels. Diabetes, 45(Suppl 3), S27–S30.PubMedGoogle Scholar
  15. 15.
    Haffner, S. M., Mykkanen, L., Festa, A., Burke, J. P., & Stern, M. P. (2000). Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin-sensitive prediabetic subjects: implications for preventing coronary heart disease during the prediabetic state. Circulation, 101(9), 975–980.PubMedCrossRefGoogle Scholar
  16. 16.
    Gordon, D. J., & Rifkind, B. M. (1989). High-density lipoprotein—the clinical implications of recent studies. The New England Journal of Medicine, 321(19), 1311–1316.PubMedCrossRefGoogle Scholar
  17. 17.
    Austin, M. A., Breslow, J. L., Hennekens, C. H., Buring, J. E., Willett, W. C., & Krauss, R. M. (1988). Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA: The Journal of the American Medical Association, 260(13), 1917–1921.CrossRefGoogle Scholar
  18. 18.
    Watts, G. F., & Karpe, F. (2011). Triglycerides and atherogenic dyslipidaemia: extending treatment beyond statins in the high-risk cardiovascular patient. Heart, 97(5), 350–356.PubMedCrossRefGoogle Scholar
  19. 19.
    Jaleel, A., Henderson, G. C., Madden, B. J., Klaus, K. A., Morse, D. M., Gopala, S., & Nair, K. S. (2010). Identification of de novo synthesized and relatively older proteins: accelerated oxidative damage to de novo synthesized apolipoprotein a-1 in type 1 diabetes. Diabetes, 59(10), 2366–2374.PubMedCrossRefGoogle Scholar
  20. 20.
    Boemi, M., Leviev, I., Sirolla, C., Pieri, C., Marra, M., & James, R. W. (2001). Serum paraoxonase is reduced in type 1 diabetic patients compared to non-diabetic, first degree relatives; influence on the ability of hdl to protect ldl from oxidation. Atherosclerosis, 155(1), 229–235.PubMedCrossRefGoogle Scholar
  21. 21.
    Mastorikou, M., Mackness, M., & Mackness, B. (2006). Defective metabolism of oxidized phospholipid by HDL from people with type 2 diabetes. Diabetes, 55(11), 3099–3103.PubMedCrossRefGoogle Scholar
  22. 22.
    Ceriello, A., Taboga, C., Tonutti, L., Quagliaro, L., Piconi, L., Bais, B., Da Ros, R., & Motz, E. (2002). Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation, 106(10), 1211–1218.PubMedCrossRefGoogle Scholar
  23. 23.
    Morishita, R., Nakamura, S., Nakamura, Y., Aoki, M., Moriguchi, A., Kida, I., Yo, Y., Matsumoto, K., Nakamura, T., Higaki, J., & Ogihara, T. (1997). Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes. Diabetes, 46(1), 138–142.PubMedCrossRefGoogle Scholar
  24. 24.
    Lehto, S., Niskanen, L., Suhonen, M., Ronnemaa, T., & Laakso, M. (1996). Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology, 16(8), 978–983.PubMedCrossRefGoogle Scholar
  25. 25.
    Mazurek, T., Zhang, L., Zalewski, A., Mannion, J. D., Diehl, J. T., Arafat, H., Sarov-Blat, L., O'Brien, S., Keiper, E. A., Johnson, A. G., Martin, J., Goldstein, B. J., & Shi, Y. (2003). Human epicardial adipose tissue is a source of inflammatory mediators. Circulation, 108(20), 2460–2466.PubMedCrossRefGoogle Scholar
  26. 26.
    Wang, C. P., Hsu, H. L., Hung, W. C., Yu, T. H., Chen, Y. H., Chiu, C. A., Lu, L. F., Chung, F. M., Shin, S. J., & Lee, Y. J. (2009). Increased epicardial adipose tissue (EAT) volume in type 2 diabetes mellitus and association with metabolic syndrome and severity of coronary atherosclerosis. Clinical Endocrinology, 70(6), 876–882.PubMedCrossRefGoogle Scholar
  27. 27.
    Baker, A. R., Silva, N. F., Quinn, D. W., Harte, A. L., Pagano, D., Bonser, R. S., Kumar, S., & McTernan, P. G. (2006). Human epicardial adipose tissue expresses a pathogenic profile of adipocytokines in patients with cardiovascular disease. Cardiovascular Diabetology, 5, 1.PubMedCrossRefGoogle Scholar
  28. 28.
    Marchant, B., Umachandran, V., Stevenson, R., Kopelman, P. G., & Timmis, A. D. (1993). Silent myocardial ischemia: role of subclinical neuropathy in patients with and without diabetes. Journal of the American College of Cardiology, 22(5), 1433–1437.PubMedCrossRefGoogle Scholar
  29. 29.
    Kronmal, R. A., Barzilay, J. I., Tracy, R. P., Savage, P. J., Orchard, T. J., & Burke, G. L. (2004). The relationship of fasting serum radioimmune insulin levels to incident coronary heart disease in an insulin-treated diabetic cohort. Journal of Clinical Endocrinology and Metabolism, 89(6), 2852–2858.PubMedCrossRefGoogle Scholar
  30. 30.
    Gerstein, H. C., Miller, M. E., Byington, R. P., Goff, D. C., Jr., Bigger, J. T., Buse, J. B., Cushman, W. C., Genuth, S., Ismail-Beigi, F., Grimm, R. H., Jr., Probstfield, J. L., Simons-Morton, D. G., & Friedewald, W. T. (2008). Effects of intensive glucose lowering in type 2 diabetes. The New England Journal of Medicine, 358(24), 2545–2559.PubMedCrossRefGoogle Scholar
  31. 31.
    Patel, A., MacMahon, S., Chalmers, J., Neal, B., Billot, L., Woodward, M., Marre, M., Cooper, M., Glasziou, P., Grobbee, D., Hamet, P., Harrap, S., Heller, S., Liu, L., Mancia, G., Mogensen, C. E., Pan, C., Poulter, N., Rodgers, A., Williams, B., Bompoint, S., de Galan, B. E., Joshi, R., & Travert, F. (2008). Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The New England Journal of Medicine, 358(24), 2560–2572.PubMedCrossRefGoogle Scholar
  32. 32.
    Skyler, J. S., Bergenstal, R., Bonow, R. O., Buse, J., Deedwania, P., Gale, E. A., Howard, B. V., Kirkman, M. S., Kosiborod, M., Reaven, P., & Sherwin, R. S. (2009). Intensive glycemic control and the prevention of cardiovascular events: implications of the accord, advance, and va diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation, 119(2), 351–357.PubMedCrossRefGoogle Scholar
  33. 33.
    Gaede, P., Vedel, P., Larsen, N., Jensen, G. V., Parving, H. H., & Pedersen, O. (2003). Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. The New England Journal of Medicine, 348(5), 383–393.PubMedCrossRefGoogle Scholar
  34. 34.
    Goldberg, R. B., Mellies, M. J., Sacks, F. M., Moye, L. A., Howard, B. V., Howard, W. J., Davis, B. R., Cole, T. G., Pfeffer, M. A., & Braunwald, E. (1998). Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. The Care Investigators. Circulation, 98(23), 2513–2519.PubMedCrossRefGoogle Scholar
  35. 35.
    The Scandinavian Simvastatin Survival Study (4s) (1994). Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease. Lancet, 344(8934), 1383–1389.Google Scholar
  36. 36.
    Pyorala, K., Pedersen, T. R., Kjekshus, J., Faergeman, O., Olsson, A. G., & Thorgeirsson, G. (1997). Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4s). Diabetes Care, 20(4), 614–620.PubMedCrossRefGoogle Scholar
  37. 37.
    The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. (1998). Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med, 339(19), 1349–1357.Google Scholar
  38. 38.
    Heart Outcomes Prevention Evaluation Study Investigators. (2000). Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE Study and Micro-HOPE Substudy. Lancet 355(9200), 253–259.Google Scholar
  39. 39.
    Lindholm, L. H., Ibsen, H., Dahlof, B., Devereux, R. B., Beevers, G., de Faire, U., Fyhrquist, F., Julius, S., Kjeldsen, S. E., Kristiansson, K., Lederballe-Pedersen, O., Nieminen, M. S., Omvik, P., Oparil, S., Wedel, H., Aurup, P., Edelman, J., & Snapinn, S. (2002). Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a randomised trial against atenolol. Lancet, 359(9311), 1004–1010.PubMedCrossRefGoogle Scholar
  40. 40.
    Investigators, B. A. R. I. (2007). The final 10-year follow-up results from the BARI randomized trial. Journal of the American College of Cardiology, 49(15), 1600–1606.CrossRefGoogle Scholar
  41. 41.
    Banning, A. P., Westaby, S., Morice, M. C., Kappetein, A. P., Mohr, F. W., Berti, S., Glauber, M., Kellett, M. A., Kramer, R. S., Leadley, K., Dawkins, K. D., & Serruys, P. W. (2010). Diabetic and nondiabetic patients with left main and/or 3-vessel coronary artery disease: comparison of outcomes with cardiac surgery and paclitaxel-eluting stents. Journal of the American College of Cardiology, 55(11), 1067–1075.PubMedCrossRefGoogle Scholar
  42. 42.
    Chaitman, B. R., Hardison, R. M., Adler, D., Gebhart, S., Grogan, M., Ocampo, S., Sopko, G., Ramires, J. A., Schneider, D., & Frye, R. L. (2009). The bypass angioplasty revascularization investigation 2 diabetes randomized trial of different treatment strategies in type 2 diabetes mellitus with stable ischemic heart disease: impact of treatment strategy on cardiac mortality and myocardial infarction. Circulation, 120(25), 2529–2540.PubMedCrossRefGoogle Scholar
  43. 43.
    Levy, D., Larson, M. G., Vasan, R. S., Kannel, W. B., & Ho, K. K. (1996). The progression from hypertension to congestive heart failure. JAMA: The Journal of the American Medical Association, 275(20), 1557–1562.CrossRefGoogle Scholar
  44. 44.
    Owan, T. E., Hodge, D. O., Herges, R. M., Jacobsen, S. J., Roger, V. L., & Redfield, M. M. (2006). Trends in prevalence and outcome of heart failure with preserved ejection fraction. The New England Journal of Medicine, 355(3), 251–259.PubMedCrossRefGoogle Scholar
  45. 45.
    Havranek, E. P., Masoudi, F. A., Westfall, K. A., Wolfe, P., Ordin, D. L., & Krumholz, H. M. (2002). Spectrum of heart failure in older patients: results from the national heart failure project. American Heart Journal, 143(3), 412–417.PubMedCrossRefGoogle Scholar
  46. 46.
    Nichols, G. A., Hillier, T. A., Erbey, J. R., & Brown, J. B. (2001). Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care, 24(9), 1614–1619.PubMedCrossRefGoogle Scholar
  47. 47.
    Kannel, W. B., Hjortland, M., & Castelli, W. P. (1974). Role of diabetes in congestive heart failure: the Framingham Study. The American Journal of Cardiology, 34, 29–34.PubMedCrossRefGoogle Scholar
  48. 48.
    Hamby, R. I., Zoneraich, S., & Sherman, S. (1974). Diabetic cardiomyopathy. JAMA: The Journal of the American Medical Association, 229, 1749–1754.CrossRefGoogle Scholar
  49. 49.
    Griffin, J. A., Osborn, B. W., & Smithline, H. A. (2005). The impact of diabetes on hospital admissions, length of stay and mortality in emergency department patients with acute decompensated heart failure without ischemia. Academic Emergency Medicine, 12, s97.CrossRefGoogle Scholar
  50. 50.
    Das, S. R., Drazner, M. H., Yancy, C. W., Stevenson, L. W., Gersh, B. J., & Dries, D. L. (2004). Effects of diabetes mellitus and ischemic heart disease on the progression from asymptomatic left ventricular dysfunction to symptomatic heart failure: a retrospective analysis from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention trial. American Heart Journal, 148(5), 883–888.PubMedCrossRefGoogle Scholar
  51. 51.
    Fein, F. S., & Sonnenblick, E. H. (1985). Diabetic cardiomyopathy. Progress in Cardiovascular Diseases, 27(4), 255–270.PubMedCrossRefGoogle Scholar
  52. 52.
    Fein, F. S. (1990). Diabetic cardiomyopathy. Diabetes Care, 13(11), 1169–1179.PubMedCrossRefGoogle Scholar
  53. 53.
    Fischer, M., Baessler, A., Hense, H. W., Hengstenberg, C., Muscholl, M., Holmer, S., Doring, A., Broeckel, U., Riegger, G., & Schunkert, H. (2003). Prevalence of left ventricular diastolic dysfunction in the community. Results from a doppler echocardiographic-based survey of a population sample. European Heart Journal, 24, 320–328.PubMedCrossRefGoogle Scholar
  54. 54.
    Boyer, J. K., Thanigaraj, H., Schectman, K. B., & Perez, J. E. (2004). Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus. The American Journal of Cardiology, 93, 870–875.PubMedCrossRefGoogle Scholar
  55. 55.
    Di Bonito, P., Cuomo, S., Moio, N., Sibilio, G., Sabatini, D., Quattrin, S., & Capaldo, B. (1996). Diastolic dysfunction in patients with non-insulin-dependent diabetes mellitus of short duration. Diabetic Medicine, 13(4), 321–324.PubMedCrossRefGoogle Scholar
  56. 56.
    Schannwell, C. M., Schneppenheim, M., Perings, S., Plehn, G., & Strauer, B. E. (2002). Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy. Cardiology, 98, 33–39.PubMedCrossRefGoogle Scholar
  57. 57.
    Peterson, L. R., Waggoner, A. D., De las Fuentes, L., Schechtman, K. B., McGill, J. B., Gropler, R. J., & Davila-Roman, V. G. (2006). Alterations in left ventricular structure and function in type-1 diabetics: a focus on left atrial contribution to function. Journal of the American Society of Echocardiography, 19(6), 749–755.PubMedCrossRefGoogle Scholar
  58. 58.
    Andersen, N. H., Poulsen, S. H., Eiskjaer, H., Poulsen, P. L., & Mogensen, C. E. (2003). Decreased left ventricular longitudinal contraction in normotensive and normoalbuminuric patients with type ii diabetes mellitus: a Doppler tissue tracking and strain rate echocardiography study. Clinical Science (London, England), 105(1), 59–66.CrossRefGoogle Scholar
  59. 59.
    Ernande, L., Rietzschel, E. R., Bergerot, C., De Buyzere, M. L., Schnell, F., Groisne, L., Ovize, M., Croisille, P., Moulin, P., Gillebert, T. C., & Derumeaux, G. (2010). Impaired myocardial radial function in asymptomatic patients with type 2 diabetes mellitus: a speckle-tracking imaging study. Journal of the American Society of Echocardiography, 23(12), 1266–1272.PubMedCrossRefGoogle Scholar
  60. 60.
    Ng, A. C., Delgado, V., Bertini, M., van der Meer, R. W., Rijzewijk, L. J., Shanks, M., Nucifora, G., Smit, J. W., Diamant, M., Romijn, J. A., de Roos, A., Leung, D. Y., Lamb, H. J., & Bax, J. J. (2009). Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus. The American Journal of Cardiology, 104(10), 1398–1401.PubMedCrossRefGoogle Scholar
  61. 61.
    Fang, Z. Y., Schull-Meade, R., Downey, M., Prins, J., & Marwick, T. H. (2005). Determinants of subclinical diabetic heart disease. Diabetologia, 48(2), 394–402.PubMedCrossRefGoogle Scholar
  62. 62.
    Carugo, S., Giannattasio, C., Calchera, I., Paleari, F., Gorgoglione, M. G., Grappiolo, A., Gamba, P., Rovaris, G., Failla, M., & Mancia, G. (2001). Progression of functional and structural cardiac alterations in young normotensive uncomplicated patients with type 1 diabetes mellitus. Journal of Hypertension, 19(9), 1675–1680.PubMedCrossRefGoogle Scholar
  63. 63.
    Galderisi, M., Anderson, K. M., Wilson, P. W., & Levy, D. (1991). Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). The American Journal of Cardiology, 68(1), 85–89.PubMedCrossRefGoogle Scholar
  64. 64.
    Tenenbaum, A., Fisman, E. Z., Schwammenthal, E., Adler, Y., Benderly, M., Motro, M., & Shemesh, J. (2003). Increased prevalence of left ventricular hypertrophy in hypertensive women with type 2 diabetes mellitus. Cardiovascular Diabetology, 2, 4.PubMedCrossRefGoogle Scholar
  65. 65.
    Lee, M., Gardin, J. M., Lynch, J. C., Smith, V. E., Tracy, R. P., Savage, P. J., Szklo, M., & Ward, B. J. (1997). Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: the Cardiovascular Health Study. American Heart Journal, 133, 36–43.PubMedCrossRefGoogle Scholar
  66. 66.
    Devereux, R. B., Roman, M. J., Paranicas, M., O'Grady, M. J., Lee, E. T., Welty, T. K., Fabsitz, R. R., Robbins, D., Rhoades, E. R., & Howard, B. V. (2000). Impact of diabetes on cardiac structure and function: the Strong Heart Study. Circulation, 101(19), 2271–2276.PubMedCrossRefGoogle Scholar
  67. 67.
    Zarich, S. W., Arbuckle, B. E., Cohen, L. R., Roberts, M., & Nesto, R. W. (1988). Diastolic abnormalities in young asymptomatic diabetic patients assessed by pulsed doppler echocardiography. Journal of the American College of Cardiology, 12, 114–120.PubMedCrossRefGoogle Scholar
  68. 68.
    Zarich, S. W., & Nesto, R. W. (1989). Diabetic cardiomyopathy. American Heart Journal, 118, 1000–1012.PubMedCrossRefGoogle Scholar
  69. 69.
    Celentano, A., Vaccaro, O., Tammaro, P., Galderisi, M., Crivaro, M., Oliviero, M., Imperatore, G., Palmieri, V., Iovino, B., & Riccardi, G. (1995). Early abnormalities of cardiac function in non-insulin-dependent diabetes mellitus and impaired glucose tolerance. The American Journal of Cardiology, 76, 1173–1176.PubMedCrossRefGoogle Scholar
  70. 70.
    Mustonen, J. N., Uusitupa, M. I., Laakso, M., Vanninen, E., Lansimies, E., Kuikka, J. T., & Pyorala, K. (1994). Left ventricular systolic function in middle-aged patients with diabetes mellitus. The American Journal of Cardiology, 73, 1202–1208.PubMedCrossRefGoogle Scholar
  71. 71.
    From, A. M., Scott, C. G., & Chen, H. H. (2010). The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction: a population-based study. Journal of the American College of Cardiology, 55(4), 300–305.PubMedCrossRefGoogle Scholar
  72. 72.
    Takeda, Y., Sakata, Y., Mano, T., Ohtani, T., Kamimura, D., Tamaki, S., Omori, Y., Tsukamoto, Y., Aizawa, Y., Komuro, I., & Yamamoto, K. (2011). Competing risks of heart failure with preserved ejection fraction in diabetic patients. European Journal of Heart Failure, 13(6), 664–669.PubMedCrossRefGoogle Scholar
  73. 73.
    Parissis, J. T., Rafouli-Stergiou, P., Mebazaa, A., Ikonomidis, I., Bistola, V., Nikolaou, M., Meas, T., Delgado, J., Vilas-Boas, F., Paraskevaidis, I., Anastasiou-Nana, M., & Follath, F. (2012). Acute heart failure in patients with diabetes mellitus: clinical characteristics and predictors of in-hospital mortality. Int J Cardiol, 157, 108–113.Google Scholar
  74. 74.
    Masoudi, F. A., & Inzucchi, S. E. (2007). Diabetes mellitus and heart failure: epidemiology, mechanisms, and pharmacotherapy. The American Journal of Cardiology, 99(4A), 113B–132B.PubMedCrossRefGoogle Scholar
  75. 75.
    Komajda, M., Carson, P. E., Hetzel, S., McKelvie, R., McMurray, J., Ptaszynska, A., Zile, M. R., Demets, D., & Massie, B. M. (2011). Factors associated with outcome in heart failure with preserved ejection fraction: findings from the Irbesartan in Heart Failure with Preserved Ejection Fraction Study (I-Preserve). Circulation. Heart Failure, 4(1), 27–35.PubMedCrossRefGoogle Scholar
  76. 76.
    Davis, B. R., Piller, L. B., Cutler, J. A., Furberg, C., Dunn, K., Franklin, S., Goff, D., Leenen, F., Mohiuddin, S., Papademetriou, V., Proschan, M., Ellsworth, A., Golden, J., Colon, P., & Crow, R. (2006). Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation, 113(18), 2201–2210.PubMedCrossRefGoogle Scholar
  77. 77.
    Domanski, M., Krause-Steinrauf, H., Deedwania, P., Follmann, D., Ghali, J. K., Gilbert, E., Haffner, S., Katz, R., Lindenfeld, J., Lowes, B. D., Martin, W., McGrew, F., & Bristow, M. R. (2003). The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. Journal of the American College of Cardiology, 42(5), 914–922.PubMedCrossRefGoogle Scholar
  78. 78.
    Giacco, F., & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation Research, 107(9), 1058–1070.PubMedCrossRefGoogle Scholar
  79. 79.
    Perez, J. E., McGill, J. B., Santiago, J. V., Schechtman, K. B., Waggoner, A. D., Miller, J. G., & Sobel, B. E. (1992). Abnormal myocardial acoustic properties in diabetic patients and their correlation with the severity of disease. Journal of the American College of Cardiology, 19, 1154–1162.PubMedCrossRefGoogle Scholar
  80. 80.
    Barzilay, J. I., Kronmal, R. A., Gottdiener, J. S., Smith, N. L., Burke, G. L., Tracy, R., Savage, P. J., & Carlson, M. (2004). The association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study. Journal of the American College of Cardiology, 43(12), 2236–2241.PubMedCrossRefGoogle Scholar
  81. 81.
    Iribarren, C., Karter, A. J., Go, A. S., Ferrara, A., Liu, J. Y., Sidney, S., & Selby, J. V. (2001). Glycemic control and heart failure among adult patients with diabetes. Circulation, 103(22), 2668–2673.PubMedCrossRefGoogle Scholar
  82. 82.
    Frustaci, A., Kajstura, J., Chimenti, C., Jakoniuk, I., Leri, A., Maseri, A., Nadal-Ginard, B., & Anversa, P. (2000). Myocardial cell death in human diabetes. Circulation Research, 87, 1123–1132.PubMedCrossRefGoogle Scholar
  83. 83.
    Anderson, E. J., Kypson, A. P., Rodriguez, E., Anderson, C. A., Lehr, E. J., & Neufer, P. D. (2009). Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. Journal of the American College of Cardiology, 54(20), 1891–1898.PubMedCrossRefGoogle Scholar
  84. 84.
    Young, M., McNulty, P., & Taegtmeyer, H. (2002). Adaptation and maladaptation of the heart in diabetes: part II: potential mechanisms. Circulation, 105, 1861–1870.PubMedCrossRefGoogle Scholar
  85. 85.
    Horowitz, J., & Klein, S. (2000). Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper body obese women. American Journal of Physiology, 278, E1144–E1152.PubMedGoogle Scholar
  86. 86.
    Groop, L. C., Bonadonna, R. C., Del Prato, S., Ratheiser, K., Zyck, K., Ferrannini, E., & DeFronzo, R. A. (1989). Glucose and free fatty acid metabolism in non-insulin dependent diabetes mellitus: evidence for multiple sites of insulin resistance. The Journal of Clinical Investigation, 84, 205–213.PubMedCrossRefGoogle Scholar
  87. 87.
    Miles, J. M., Wooldridge, D., Grellner, W. J., Windsor, S., Isley, W. L., Klein, S., & Harris, W. S. (2003). Nocturnal and postprandial free fatty acid kinetics in normal and type 2 diabetic subjects. Diabetes, 52, 675–681.PubMedCrossRefGoogle Scholar
  88. 88.
    Peterson, L. R., Herrero, P., Schechtman, K. B., Racette, S. B., Waggoner, A. D., Kisrieva-Ware, Z., Dence, C., Klein, S., Marsala, J., Meyer, T., & Gropler, R. J. (2004). Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation, 109, 2191–2196.PubMedCrossRefGoogle Scholar
  89. 89.
    Herrero, P., Peterson, L. R., McGill, J. B., Matthew, S., Lesniak, D., Dence, C., & Gropler, R. J. (2006). Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. Journal of the American College of Cardiology, 47(3), 598–604.PubMedCrossRefGoogle Scholar
  90. 90.
    Diamant, M., Lamb, H., Groeneveld, Y., Endert, E., Smit, J., Bax, J., Romijn, J., de Roos, A., & Radder, J. (2003). Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. Journal of the American College of Cardiology, 42, 328–335.PubMedCrossRefGoogle Scholar
  91. 91.
    Scheuermann-Freestone, M., Madsen, P. L., Manners, D., Blamire, A. M., Buckingham, R. E., Styles, P., Radda, G. K., Neubauer, S., & Clarke, K. (2003). Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation, 107, 3040–3046.PubMedCrossRefGoogle Scholar
  92. 92.
    Szczepaniak, L. S., Dibbins, R. L., Metzger, G. J., Sartoni-D'Ambrosia, G., Arbique, D., Vongpatanasin, W., Unger, R., & Victor, R. G. (2003). Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging. Magnetic Resonance in Medicine, 49, 417–423.PubMedCrossRefGoogle Scholar
  93. 93.
    Alavaikko, M., Elfving, R., Hirvonen, E. J., & Jarvi, J. (1973). Triglycerides, cholesterol, and phospholipids in normal heart papillary muscle and inpatients suffering from diabetes, cholelithiasis, hypertension, and coronary atheroma. Journal of Clinical Pathology, 26, 285–293.PubMedCrossRefGoogle Scholar
  94. 94.
    Sharma, S., Adrogue, J. V., Golfman, L., Uray, I., Lemm, J., Youker, K., Noon, G. P., Frazier, O. H., & Taegtmeyer, H. (2004). Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. The FASEB Journal, 18, 1692–1700.CrossRefGoogle Scholar
  95. 95.
    Leinonen, J., Lehtimaki, T., Toyokuni, S., Okada, K., Tanaka, T., Hiai, H., Ochi, H., Laippala, P., Rantalaiho, V., Wirta, O., Pasternack, A., & Alho, H. (1997). New biomarker evidence of oxidative DNA damage in patients with non-insulin-dependent diabetes mellitus. FEBS Letters, 417(1), 150–152.PubMedCrossRefGoogle Scholar
  96. 96.
    Murakami, K., Kondo, T., Ohtsuka, Y., Fujiwara, Y., Shimada, M., & Kawakami, Y. (1989). Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism, 38(8), 753–758.PubMedCrossRefGoogle Scholar
  97. 97.
    Nourooz-Zadeh, J., Tajaddini-Sarmadi, J., McCarthy, S., Betteridge, D. J., & Wolff, S. P. (1995). Elevated levels of authentic plasma hydroperoxides in NIDDM. Diabetes, 44(9), 1054–1058.PubMedCrossRefGoogle Scholar
  98. 98.
    El-Mesallamy, H., Hamdy, N., Suwailem, S., & Mostafa, S. (2010). Oxidative stress and platelet activation: markers of myocardial infarction in type 2 diabetes mellitus. Angiology, 61(1), 14–18.PubMedCrossRefGoogle Scholar
  99. 99.
    Iacobellis, G., Ribaudo, M. C., Zappaterreno, A., Vecci, E., Tiberti, C., Di Mario, U., & Leonetti, F. (2003). Relationship of insulin sensitivity and left ventricular mass in uncomplicated obesity. Obesity Research, 11(4), 518–524.PubMedCrossRefGoogle Scholar
  100. 100.
    Rutter, M. K., Parise, H., Benjamin, E. J., Levy, D., Larson, M. G., Meigs, J. B., Nesto, R. W., Wilson, P. W., & Vasan, R. S. (2003). Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation, 107(3), 448–454.PubMedCrossRefGoogle Scholar
  101. 101.
    Abel, E. D. (2004). Insulin signaling in heart muscle: lessons from genetically engineered mouse models. Current Hypertension Reports, 6(6), 416–423.PubMedCrossRefGoogle Scholar
  102. 102.
    Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, et al. (2002). Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA: The Journal of the American Medical Association, 287(19), 2563–2569.CrossRefGoogle Scholar
  103. 103.
    UK Prospective Diabetes Study (UKPDS) Group, et al. (1998). Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet, 352(9131), 837–853.CrossRefGoogle Scholar
  104. 104.
    Holman, R. R., Paul, S. K., Bethel, M. A., Matthews, D. R., & Neil, H. A. (2008). 10-year follow-up of intensive glucose control in type 2 diabetes. The New England Journal of Medicine, 359(15), 1577–1589.PubMedCrossRefGoogle Scholar
  105. 105.
    Stratton, I. M., Adler, A. I., Neil, H. A., Matthews, D. R., Manley, S. E., Cull, C. A., Hadden, D., Turner, R. C., & Holman, R. R. (2000). Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ, 321(7258), 405–412.PubMedCrossRefGoogle Scholar
  106. 106.
    Shekelle, P. G., Rich, M. W., Morton, S. C., Atkinson, C. S., Tu, W., Maglione, M., Rhodes, S., Barrett, M., Fonarow, G. C., Greenberg, B., Heidenreich, P. A., Knabel, T., Konstam, M. A., Steimle, A., & Warner Stevenson, L. (2003). Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status: a meta-analysis of major clinical trials. Journal of the American College of Cardiology, 41(9), 1529–1538.PubMedCrossRefGoogle Scholar
  107. 107.
    Hunt, S. A., Baker, D. W., Chin, M. H., Cinquegrani, M. P., Feldman, A. M., Francis, G. S., Ganiats, T. G., Goldstein, S., Gregoratos, G., Jessup, M. L., Noble, R. J., Packer, M., Silver, M. A., Stevenson, L. W., Gibbons, R. J., Antman, E. M., Alpert, J. S., Faxon, D. P., Fuster, V., Jacobs, A. K., Hiratzka, L. F., Russell, R. O., & Smith, S. C., Jr. (2001). Acc/aha guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). Journal of the American College of Cardiology, 38(7), 2101–2113.PubMedCrossRefGoogle Scholar
  108. 108.
    Hou, F. F., Zhang, X., Zhang, G. H., Xie, D., Chen, P. Y., Zhang, W. R., Jiang, J. P., Liang, M., Wang, G. B., Liu, Z. R., & Geng, R. W. (2006). Efficacy and safety of benazepril for advanced chronic renal insufficiency. The New England Journal of Medicine, 354(2), 131–140.PubMedCrossRefGoogle Scholar
  109. 109.
    Masoudi, F. A., & Havranek, E. P. (2001). Race and responsiveness to drugs for heart failure. The New England Journal of Medicine, 345(10), 767. author reply 767-8.PubMedGoogle Scholar
  110. 110.
    Lindholm, L. H., Ibsen, H., Borch-Johnsen, K., Olsen, M. H., Wachtell, K., Dahlof, B., Devereux, R. B., Beevers, G., de Faire, U., Fyhrquist, F., Julius, S., Kjeldsen, S. E., Kristianson, K., Lederballe-Pedersen, O., Nieminen, M. S., Omvik, P., Oparil, S., Wedel, H., Aurup, P., Edelman, J. M., & Snapinn, S. (2002). Risk of new-onset diabetes in the losartan intervention for endpoint reduction in hypertension study. Journal of Hypertension, 20(9), 1879–1886.PubMedCrossRefGoogle Scholar
  111. 111.
    Pitt, B., Zannad, F., Remme, W. J., Cody, R., Castaigne, A., Perez, A., Palensky, J., & Wittes, J. (1999). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. The New England Journal of Medicine, 341(10), 709–717.PubMedCrossRefGoogle Scholar
  112. 112.
    Pitt, B., Remme, W., Zannad, F., Neaton, J., Martinez, F., Roniker, B., Bittman, R., Hurley, S., Kleiman, J., & Gatlin, M. (2003). Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. The New England Journal of Medicine, 348(14), 1309–1321.PubMedCrossRefGoogle Scholar
  113. 113.
    Packer, M., Coats, A. J., Fowler, M. B., Katus, H. A., Krum, H., Mohacsi, P., Rouleau, J. L., Tendera, M., Castaigne, A., Roecker, E. B., Schultz, M. K., & DeMets, D. L. (2001). Effect of carvedilol on survival in severe chronic heart failure. The New England Journal of Medicine, 344(22), 1651–1658.PubMedCrossRefGoogle Scholar
  114. 114.
    Kirpichnikov, D., McFarlane, S. I., & Sowers, J. R. (2003). Heart failure in diabetic patients: utility of beta-blockade. Journal of Cardiac Failure, 9(4), 333–344.PubMedCrossRefGoogle Scholar
  115. 115.
    Rhenman, M. J., Rhenman, B., Icenogle, T., Christensen, R., & Copeland, J. (1988). Diabetes and heart transplantation. The Journal of Heart Transplantation, 7(5), 356–358.PubMedGoogle Scholar
  116. 116.
    Marelli, D., Laks, H., Patel, B., Kermani, R., Marmureanu, A., Patel, J., & Kobashigawa, J. (2003). Heart transplantation in patients with diabetes mellitus in the current era. The Journal of Heart and Lung Transplantation, 22(10), 1091–1097.PubMedCrossRefGoogle Scholar
  117. 117.
    Higgins, J., Pflugfelder, P. W., & Kostuk, W. J. (2009). Increased morbidity in diabetic cardiac transplant recipients. Canadian Journal of Cardiology, 25(4), e125–e129.PubMedCrossRefGoogle Scholar
  118. 118.
    Hunt, S. A. (2005). ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to update the 2001 guidelines for the evaluation and management of heart failure). Journal of the American College of Cardiology, 46(6), e1–e82.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Linda R. Peterson
    • 1
  • Clark R. McKenzie
    • 2
  • Jean E. Schaffer
    • 1
  1. 1.Diabetic Cardiovascular Disease Center, Department of MedicineWashington UniversitySt. LouisUSA
  2. 2.Mercy Clinic Heart and VascularSt. LouisUSA

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