Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Heart failure in diabetes mellitus

Richard W Nesto, MD
Section Editors
Wilson S Colucci, MD
David M Nathan, MD
Deputy Editors
Susan B Yeon, MD, JD, FACC
Jean E Mulder, MD


Diabetes mellitus (DM) increases the risk of heart failure (HF) independent of coronary heart disease and hypertension and may cause a cardiomyopathy. The term “diabetic cardiomyopathy” was initially introduced based upon postmortem findings in four diabetic adults who had HF in the absence of coronary heart disease [1].

Diabetic cardiomyopathy has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause (eg, coronary heart disease, hypertension) [2,3]. However, the frequency with which this occurs is not well defined and there is some evidence that diabetic cardiomyopathy is uncommon in patients with type 1 diabetes in the era of intensive insulin therapy [4].

Issues related to HF in diabetic patients will be reviewed here. The prevalence of and risk factors for coronary heart disease among patients with DM and the evaluation and treatment of HF are discussed separately. (See "Prevalence of and risk factors for coronary heart disease in diabetes mellitus" and "Evaluation of the patient with suspected heart failure" and "Overview of the therapy of heart failure with reduced ejection fraction" and "Treatment and prognosis of heart failure with preserved ejection fraction".)


There is a well-established association between diabetes mellitus (DM) and heart failure (HF) that is partly but not entirely linked to coronary heart disease and hypertension. Associations have also been reported between absolute blood glucose levels, glycemic control, and HF.

Diabetes and HF — The Framingham Study firmly established the epidemiologic link between diabetes and HF [5]. The risk of HF was increased 2.4-fold in men and fivefold in women. Diabetes predicted HF independent of coexisting hypertension or coronary disease. When patients with prior coronary or rheumatic heart disease were excluded, the relative risk of HF remained elevated at 3.8 in diabetic men and 5.5 in diabetic women.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Nov 02, 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Rubler S, Dlugash J, Yuceoglu YZ, et al. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30:595.
  2. Zarich SW, Nesto RW. Diabetic cardiomyopathy. Am Heart J 1989; 118:1000.
  3. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007; 115:3213.
  4. Konduracka E, Gackowski A, Rostoff P, et al. Diabetes-specific cardiomyopathy in type 1 diabetes mellitus: no evidence for its occurrence in the era of intensive insulin therapy. Eur Heart J 2007; 28:2465.
  5. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974; 34:29.
  6. Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001; 24:1614.
  7. Bertoni AG, Hundley WG, Massing MW, et al. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care 2004; 27:699.
  8. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001; 103:2668.
  9. Bertoni AG, Tsai A, Kasper EK, Brancati FL. Diabetes and idiopathic cardiomyopathy: a nationwide case-control study. Diabetes Care 2003; 26:2791.
  10. Nichols GA, Gullion CM, Koro CE, et al. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care 2004; 27:1879.
  11. Barzilay JI, Kronmal RA, Gottdiener JS, et al. The association of fasting glucose levels with congestive heart failure in diabetic adults > or =65 years: the Cardiovascular Health Study. J Am Coll Cardiol 2004; 43:2236.
  12. Carr AA, Kowey PR, Devereux RB, et al. Hospitalizations for new heart failure among subjects with diabetes mellitus in the RENAAL and LIFE studies. Am J Cardiol 2005; 96:1530.
  13. Halon DA, Merdler A, Flugelman MY, et al. Late-onset heart failure as a mechanism for adverse long-term outcome in diabetic patients undergoing revascularization (a 13-year report from the Lady Davis Carmel Medical Center registry). Am J Cardiol 2000; 85:1420.
  14. Greenberg BH, Abraham WT, Albert NM, et al. Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). Am Heart J 2007; 154:277.e1.
  15. Held C, Gerstein HC, Yusuf S, et al. Glucose levels predict hospitalization for congestive heart failure in patients at high cardiovascular risk. Circulation 2007; 115:1371.
  16. Lind M, Bounias I, Olsson M, et al. Glycaemic control and incidence of heart failure in 20,985 patients with type 1 diabetes: an observational study. Lancet 2011; 378:140.
  17. Control Group, Turnbull FM, Abraira C, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia 2009; 52:2288.
  18. Stone PH, Muller JE, Hartwell T, et al. 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. J Am Coll Cardiol 1989; 14:49.
  19. Vered A, Battler A, Segal P, et al. Exercise-induced left ventricular dysfunction in young men with asymptomatic diabetes mellitus (diabetic cardiomyopathy). Am J Cardiol 1984; 54:633.
  20. Arvan S, Singal K, Knapp R, Vagnucci A. Subclinical left ventricular abnormalities in young diabetics. Chest 1988; 93:1031.
  21. Galderisi M. Diastolic dysfunction and diabetic cardiomyopathy: evaluation by Doppler echocardiography. J Am Coll Cardiol 2006; 48:1548.
  22. Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000; 101:2271.
  23. Mildenberger RR, Bar-Shlomo B, Druck MN, et al. Clinically unrecognized ventricular dysfunction in young diabetic patients. J Am Coll Cardiol 1984; 4:234.
  24. Mustonen JN, Uusitupa MI, Laakso M, et al. Left ventricular systolic function in middle-aged patients with diabetes mellitus. Am J Cardiol 1994; 73:1202.
  25. Stahrenberg R, Edelmann F, Mende M, et al. Association of glucose metabolism with diastolic function along the diabetic continuum. Diabetologia 2010; 53:1331.
  26. From AM, Scott CG, Chen HH. The development of heart failure in patients with diabetes mellitus and pre-clinical diastolic dysfunction a population-based study. J Am Coll Cardiol 2010; 55:300.
  27. 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; 68:85.
  28. Liu JE, Palmieri V, Roman MJ, et al. The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study. J Am Coll Cardiol 2001; 37:1943.
  29. Fischer VW, Barner HB, Leskiw ML. Capillary basal laminar thichness in diabetic human myocardium. Diabetes 1979; 28:713.
  30. Factor SM, Okun EM, Minase T. Capillary microaneurysms in the human diabetic heart. N Engl J Med 1980; 302:384.
  31. van Hoeven KH, Factor SM. A comparison of the pathological spectrum of hypertensive, diabetic, and hypertensive-diabetic heart disease. Circulation 1990; 82:848.
  32. van Heerebeek L, Hamdani N, Handoko ML, et al. Diastolic stiffness of the failing diabetic heart: importance of fibrosis, advanced glycation end products, and myocyte resting tension. Circulation 2008; 117:43.
  33. An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 2006; 291:H1489.
  34. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation 2007; 116:434.
  35. Neubauer B, Christensen NJ. Norepinephrine, epinephrine, and dopamine contents of the cardiovascular system in long-term diabetics. Diabetes 1976; 25:6.
  36. Scognamiglio R, Avogaro A, Casara D, et al. Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 1998; 31:404.
  37. Rossen JD. Abnormal microvascular function in diabetes: relationship to diabetic cardiomyopathy. Coron Artery Dis 1996; 7:133.
  38. Johnstone MT, Creager SJ, Scales KM, et al. Impaired endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 1993; 88:2510.
  39. Bucala R, Tracey KJ, Cerami A. Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Invest 1991; 87:432.
  40. Sebbag L, Forrat R, Canet E, et al. Effect of experimental non-insulin requiring diabetes on myocardial microcirculation during ischaemia in dogs. Eur J Clin Invest 1994; 24:686.
  41. Yoon YS, Uchida S, Masuo O, et al. Progressive attenuation of myocardial vascular endothelial growth factor expression is a seminal event in diabetic cardiomyopathy: restoration of microvascular homeostasis and recovery of cardiac function in diabetic cardiomyopathy after replenishment of local vascular endothelial growth factor. Circulation 2005; 111:2073.
  42. Heymes C, Vanderheyden M, Bronzwaer JG, et al. Endomyocardial nitric oxide synthase and left ventricular preload reserve in dilated cardiomyopathy. Circulation 1999; 99:3009.
  43. Asbun J, Villarreal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol 2006; 47:693.
  44. Wheeler TJ. Translocation of glucose transporters in response to anoxia in heart. J Biol Chem 1988; 263:19447.
  45. Sun D, Nguyen N, DeGrado TR, et al. Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes. Circulation 1994; 89:793.
  46. Rodrigues B, Cam MC, McNeill JH. Myocardial substrate metabolism: implications for diabetic cardiomyopathy. J Mol Cell Cardiol 1995; 27:169.
  47. McGavock JM, Lingvay I, Zib I, et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007; 116:1170.
  48. Ruberg FL. Myocardial lipid accumulation in the diabetic heart. Circulation 2007; 116:1110.
  49. 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.
  50. Cesario DA, Brar R, Shivkumar K. Alterations in ion channel physiology in diabetic cardiomyopathy. Endocrinol Metab Clin North Am 2006; 35:601.
  51. 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.
  52. Frustaci A, Kajstura J, Chimenti C, et al. Myocardial cell death in human diabetes. Circ Res 2000; 87:1123.
  53. Cai L, Wang Y, Zhou G, et al. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J Am Coll Cardiol 2006; 48:1688.
  54. Shindler DM, Kostis JB, Yusuf S, et al. Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry. Am J Cardiol 1996; 77:1017.
  55. Dries DL, Sweitzer NK, Drazner MH, et al. Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol 2001; 38:421.
  56. Gustafsson I, Brendorp B, Seibaek M, et al. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol 2004; 43:771.
  57. Yki-Järvinen H. Thiazolidinediones. N Engl J Med 2004; 351:1106.
  58. Masoudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: an observational study. Circulation 2005; 111:583.
  59. Dargie HJ, Hildebrandt PR, Riegger GA, et al. A randomized, placebo-controlled trial assessing the effects of rosiglitazone on echocardiographic function and cardiac status in type 2 diabetic patients with New York Heart Association Functional Class I or II Heart Failure. J Am Coll Cardiol 2007; 49:1696.
  60. www.fda.gov/medwatch/SAFETY/2002/summary-actos-avandia.PDF (Accessed on March 07, 2005).
  61. Delea TE, Edelsberg JS, Hagiwara M, et al. Use of thiazolidinediones and risk of heart failure in people with type 2 diabetes: a retrospective cohort study. Diabetes Care 2003; 26:2983.
  62. Singh S, Loke YK, Furberg CD. Thiazolidinediones and heart failure: a teleo-analysis. Diabetes Care 2007; 30:2148.
  63. Lago RM, Singh PP, Nesto RW. Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials. Lancet 2007; 370:1129.
  64. Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet 2009; 373:2125.
  65. Dormandy JA, Charbonnel B, Eckland DJ, et al. 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.
  66. Wang CH, Weisel RD, Liu PP, et al. Glitazones and heart failure: critical appraisal for the clinician. Circulation 2003; 107:1350.
  67. Thomas ML, Lloyd SJ. Pulmonary edema associated with rosiglitazone and troglitazone. Ann Pharmacother 2001; 35:123.
  68. Hirsch IB, Kelly J, Cooper S. Pulmonary edema associated with troglitazone therapy. Arch Intern Med 1999; 159:1811.
  69. Karalliedde J, Buckingham R, Starkie M, et al. Effect of various diuretic treatments on rosiglitazone-induced fluid retention. J Am Soc Nephrol 2006; 17:3482.
  70. Guan Y, Hao C, Cha DR, et al. Thiazolidinediones expand body fluid volume through PPARgamma stimulation of ENaC-mediated renal salt absorption. Nat Med 2005; 11:861.
  71. Song J, Knepper MA, Hu X, et al. Rosiglitazone activates renal sodium- and water-reabsorptive pathways and lowers blood pressure in normal rats. J Pharmacol Exp Ther 2004; 308:426.
  72. Nesto RW, Bell D, Bonow RO, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 2003; 108:2941.
  73. www.fda.gov/bbs/topics/NEWS/2007/NEW01683.html (Accessed on August 15, 2007).
  74. http://www.hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2007/avandia_hpc-cps_5-eng.php. (Accessed on January 20, 2014).
  75. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008; 29:2388.
  76. Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009; 119:e391.
  77. Product information Glucophage (metformin hydrochloride) Bristol-Myers Squibb http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=8463 (Accessed on March 25, 2009).
  78. Eurich DT, Weir DL, Majumdar SR, et al. Comparative safety and effectiveness of metformin in patients with diabetes mellitus and heart failure: systematic review of observational studies involving 34,000 patients. Circ Heart Fail 2013; 6:395.
  79. Shekelle PG, Rich MW, Morton SC, et al. 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. J Am Coll Cardiol 2003; 41:1529.
  80. Moyé LA, Pfeffer MA, Wun CC, et al. Uniformity of captopril benefit in the SAVE Study: subgroup analysis. Survival and Ventricular Enlargement Study. Eur Heart J 1994; 15 Suppl B:2.
  81. van der Meer RW, Rijzewijk LJ, de Jong HW, 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; 119:2069.
  82. Horio T, Suzuki M, Suzuki K, et al. Pioglitazone improves left ventricular diastolic function in patients with essential hypertension. Am J Hypertens 2005; 18:949.
  83. Lautamäki R, Airaksinen KE, Seppänen M, et al. Rosiglitazone improves myocardial glucose uptake in patients with type 2 diabetes and coronary artery disease: a 16-week randomized, double-blind, placebo-controlled study. Diabetes 2005; 54:2787.
  84. Marelli D, Laks H, Patel B, et al. Heart transplantation in patients with diabetes mellitus in the current era. J Heart Lung Transplant 2003; 22:1091.
  85. Rhenman MJ, Rhenman B, Icenogle T, et al. Diabetes and heart transplantation. J Heart Transplant 1988; 7:356.
  86. Ladowski JS, Kormos RL, Uretsky BF, et al. Heart transplantation in diabetic recipients. Transplantation 1990; 49:303.