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The impact of diabetes on heart failure: Opportunities for intervention

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Abstract

The pathophysiologic processes of diabetes mellitus and heart failure are likely interrelated. In particular, hyperglycemia and insulin resistance can induce myocardial contractile systolic and diastolic abnormalities at the cellular level. Furthermore, patients with heart failure and concomitant diabetes mellitus are more likely to have underlying comorbid conditions resulting in greater vulnerability to adverse consequences. It is reassuring that the majority of patients with diabetes mellitus and heart failure respond to standard heart failure medical regimens comparable to their nondiabetes counterparts. However, the safety profiles of current antidiabetic medications are far from ideal when used in patients with heart failure. Emerging novel therapies that reverse the metabolic and structural changes induced by the diabetic milieu are currently under clinical development, and their potential benefits may even extend beyond the diabetic population.

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References and Recommended Reading

  1. Kannel WB, Hjortland M, Castelli WP: Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974, 34:29–34.

    Article  PubMed  CAS  Google Scholar 

  2. Nichols GA, Hillier TA, Erbey JR, Brown JB: Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001, 24:1614–1619.

    Article  PubMed  CAS  Google Scholar 

  3. Stratton IM, Adler AI, Neil HA, et al.: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000, 321:405–412.

    Article  PubMed  CAS  Google Scholar 

  4. Ingelsson E, Arnlov J, Lind L, Sundstrom J: Metabolic syndrome and risk for heart failure in middle-aged men. Heart 2006, 92:1409–1413.

    Article  PubMed  CAS  Google Scholar 

  5. Butler J, Rodondi N, Zhu Y, et al.: Metabolic syndrome and the risk of cardiovascular disease in older adults. J Am Coll Cardiol 2006, 47:1595–1602.

    Article  PubMed  Google Scholar 

  6. Horowitz JD, Kennedy JA: Time to address the cardiac metabolic “triple whammy” ischemic heart failure in diabetic patients. J Am Coll Cardiol 2006, 48:2232–2234.

    Article  PubMed  Google Scholar 

  7. Yancy CW, Lopatin M, Stevenson LW, et al.: Clinical presentation, management, and in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am Coll Cardiol 2006, 47:76–84.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  PubMed  Google Scholar 

  9. Amato L, Paolisso G, Cacciatore F, et al.: Congestive heart failure predicts the development of non-insulin-dependent diabetes mellitus in the elderly. The Osservatorio Geriatrico Regione Campania Group. Diabetes Metab 1997, 23:213–218.

    PubMed  CAS  Google Scholar 

  10. Tenenbaum A, Motro M, Fisman EZ, et al.: Functional class in patients with heart failure is associated with the development of diabetes. Am J Med 2003, 114:271–275.

    Article  PubMed  Google Scholar 

  11. Suskin N, McKelvie RS, Burns RJ, et al.: Glucose and insulin abnormalities relate to functional capacity in patients with congestive heart failure. Eur Heart J 2000, 21:1368–1375.

    Article  PubMed  CAS  Google Scholar 

  12. Poirier P, Bogaty P, Garneau C, et al.: Diastolic dysfunction in normotensive men with well-controlled type 2 diabetes: importance of maneuvers in echocardiographic screening for preclinical diabetic cardiomyopathy. Diabetes Care 2001, 24:5–10.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    PubMed  CAS  Google Scholar 

  14. Fang ZY, Prins JB, Marwick TH: Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev 2004, 25:543–567.

    Article  PubMed  CAS  Google Scholar 

  15. 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, 77:1017–1020.

    Article  PubMed  CAS  Google Scholar 

  16. 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, 38:421–428.

    Article  PubMed  CAS  Google Scholar 

  17. De Groote P, Lamblin N, Mouquet F, et al.: Impact of diabetes mellitus on long-term survival in patients with congestive heart failure. Eur Heart J 2004, 25:656–662.

    Article  PubMed  Google Scholar 

  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, 14:49–57.

    Article  PubMed  CAS  Google Scholar 

  19. Malmberg K, Norhammar A, Wedel H, Ryden L: Glyco-metabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study. Circulation 1999, 99:2626–2632.

    PubMed  CAS  Google Scholar 

  20. Stanley WC, Lopaschuk GD, McCormack JG: Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 1997, 34:25–33.

    Article  PubMed  CAS  Google Scholar 

  21. Stanley WC, Recchia FA, Lopaschuk GD: Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005, 85:1093–1129.

    Article  PubMed  CAS  Google Scholar 

  22. Butler AE, Janson J, Bonner-Weir S, et al.: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003, 52:102–110.

    Article  PubMed  CAS  Google Scholar 

  23. Carnethon MR, Golden SH, Folsom AR, et al.: Prospective investigation of autonomic nervous system function and the development of type 2 diabetes: the Atherosclerosis Risk In Communities study, 1987–1998. Circulation 2003, 107:2190–2195.

    Article  PubMed  Google Scholar 

  24. Meigs JB, Hu FB, Rifai N, Manson JE: Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004, 291:1978–1986.

    Article  PubMed  CAS  Google Scholar 

  25. Witteles RM, Tang WH, Jamali AH, et al.: Insulin resistance in idiopathic dilated cardiomyopathy: a possible etiologic link. J Am Coll Cardiol 2004, 44:78–81.

    Article  PubMed  CAS  Google Scholar 

  26. Dutka DP, Pitt M, Pagano D, et al.: Myocardial glucose transport and utilization in patients with type 2 diabetes mellitus, left ventricular dysfunction, and coronary artery disease. J Am Coll Cardiol 2006, 48:2225–2231.

    Article  PubMed  CAS  Google Scholar 

  27. Entman ML, Bornet EP, Van Winkle WB, et al.: Association of glycogenolysis with cardiac sarcoplasmic reticulum: II. Effect of glycogen depletion, deoxycholate solubilization and cardiac ischemia: evidence for a phorphorylase kinase membrane complex. J Mol Cell Cardiol 1977, 9:515–528.

    PubMed  CAS  Google Scholar 

  28. An D, Rodrigues B: Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol 2006, 291:H1489–1506.

    Article  PubMed  CAS  Google Scholar 

  29. Singal PK, Bello-Klein A, Farahmand F, Sandhawalia V: Oxidative stress and functional deficit in diabetic cardiomyopathy. Adv Exp Med Biol 2001, 498:213–220.

    PubMed  CAS  Google Scholar 

  30. Armoni M, Harel C, Bar-Yoseph F, et al.: Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem 2005, 280:34786–34795.

    Article  PubMed  CAS  Google Scholar 

  31. Mazumder PK, O’Neill BT, Roberts MW, et al.: Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts. Diabetes 2004, 53:2366–2374.

    Article  PubMed  CAS  Google Scholar 

  32. Murray AJ, Anderson RE, Watson GC, et al.: Uncoupling proteins in human heart. Lancet 2004, 364:1786–1788.

    Article  PubMed  CAS  Google Scholar 

  33. Tang WH: Glycemic control and treatment patterns in patients with heart failure. Heart Fail Monit 2006, 5:10–14.

    PubMed  CAS  Google Scholar 

  34. 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, 111:583–590.

    Article  PubMed  CAS  Google Scholar 

  35. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998, 317:703–713.

  36. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet 2000, 355:253–259.

  37. 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, 41:1529–1538.

    Article  PubMed  CAS  Google Scholar 

  38. Abuissa H, Jones PG, Marso SP, O’Keefe JH Jr: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol 2005, 46:821–826.

    Article  PubMed  CAS  Google Scholar 

  39. Bakris GL, Fonseca V, Katholi RE, et al.: Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA 2004, 292:2227–2236.

    Article  PubMed  CAS  Google Scholar 

  40. Pitt B, Zannad F, Remme WJ, et al.: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 1999, 341:709–717.

    Article  PubMed  CAS  Google Scholar 

  41. Pitt B, Remme W, Zannad F, et al.: Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003, 348:1309–1321.

    Article  PubMed  CAS  Google Scholar 

  42. Hermann HP, Pieske B, Schwarzmuller E, et al.: Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: an open study. Lancet 1999, 353:1321–1323.

    Article  PubMed  CAS  Google Scholar 

  43. Thrainsdottir I, Malmberg K, Olsson A, et al.: Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res 2004, 1:40–43.

    Article  PubMed  Google Scholar 

  44. Lee L, Campbell R, Scheuermann-Freestone M, et al.: Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 2005, 112:3280–3288.

    Article  PubMed  CAS  Google Scholar 

  45. Jeffrey FM, Alvarez L, Diczku V, et al.: Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J Cardiovasc Pharmacol 1995, 25:469–472.

    Article  PubMed  CAS  Google Scholar 

  46. Schmidt-Schweda S, Holubarsch C: First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin Sci (Lond) 2000, 99:27–35.

    Article  CAS  Google Scholar 

  47. Lionetti V, Linke A, Chandler MP, et al.: Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure. Cardiovasc Res 2005, 66:454–461.

    Article  PubMed  CAS  Google Scholar 

  48. Vitale C, Wajngaten M, Sposato B, et al.: Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease. Eur Heart J 2004, 25:1814–1821.

    Article  PubMed  CAS  Google Scholar 

  49. Di Napoli P, Taccardi AA, Barsotti A: Long term cardio-protective action of trimetazidine and potential effect on the inflammatory process in patients with ischemic dilated cardiomyopathy. Heart 2005, 91:161–165.

    Article  PubMed  CAS  Google Scholar 

  50. Fragasso G, Palloshi A, Puccetti P, et al.: A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol 2006, 48:992–998.

    Article  PubMed  CAS  Google Scholar 

  51. Thrainsdottir IS, von Bibra H, Malmberg K, Ryden L: Effects of trimetazidine on left ventricular function in patients with type 2 diabetes and heart failure. J Cardiovasc Pharmacol 2004, 44:101–108.

    Article  PubMed  CAS  Google Scholar 

  52. Chaitman BR: Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation 2006, 113:2462–2472.

    Article  PubMed  Google Scholar 

  53. Cooper GJ, Phillips AR, Choong SY, et al.: Regeneration of the heart in diabetes by selective copper chelation. Diabetes 2004, 53:2501–2508.

    Article  PubMed  CAS  Google Scholar 

  54. Liu J, Masurekar MR, Vatner DE, et al.: Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am J Physiol Heart Circ Physiol 2003, 285:H2587–2591.

    PubMed  CAS  Google Scholar 

  55. Asbun J, Villarreal FJ: The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol 2006, 47:693–700.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to W. H. Wilson Tang MD.

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Skouri, H.N., Wilson Tang, W.H. The impact of diabetes on heart failure: Opportunities for intervention. Curr Heart Fail Rep 4, 70–77 (2007). https://doi.org/10.1007/s11897-007-0003-8

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