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Impaired Glucose Metabolism in Patients with Heart Failure

Pathophysiology and Possible Treatment Strategies

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Abstract

The firm association of diabetes mellitus with congestive heart failure (CHF) has been undoubtedly established. Recent reports support the presence of the reciprocal interrelationships between CHF and glucose abnormalities. The present review provides an overview of some aspects of the multifactorial interrelationships between heart failure and diabetes mellitus. Patients with heart failure are generally at higher risk of developing type 2 diabetes mellitus. Several factors may be involved, such as a lack of physical activity, hypermetabolic state, intracellular metabolic defects, poor muscle perfusion, and poor nutrition. Serum levels of inflammatory cytokines and leptin are elevated in patients with heart failure. Activation of the sympathetic system in CHF not only increases insulin resistance but also decreases the release of insulin from the pancreatic β cells, increases hepatic glucose production by stimulating both gluconeogenesis and glycogenolysis, and increases glucagon production and lipolysis. People who develop type 2 diabetes mellitus usually pass through the phases of nuclear peroxisome proliferator-activated receptor modulation, insulin resistance, hyperinsulinemia, pancreatic β-cell stress and damage leading to progressively decreasing insulin secretion, and impaired fasting and postprandial blood glucose levels. Once hyperglycemia ensues, the risk of metabolic and cardiovascular complications also increases. It is possible that the cornerstone of diabetes mellitus prevention in patients with CHF could be controlled by increased physical activity in a cardiac rehabilitation framework. Pharmacologic interventions by some medications (metformin, orlistat, ramipril and acarbose) can also effectively delay progression to type 2 diabetes mellitus in general high risk populations, but the magnitude of the benefit in patients with CHF is unknown. In patients with CHF and overt diabetes mellitus, ACE inhibitors may provide a special advantage and should be the first-line agent. Recent reports have suggested that angiotensin receptor antagonists (angiotensin receptor blockers), similar to ACE inhibitors, provide beneficial effects in patients with diabetes mellitus and should be the second-line agent if ACE inhibitors are contraindicated. Treatment with HMG-CoA reductase inhibitors should probably now be considered routinely for all diabetic patients with CHF, irrespective of their initial serum cholesterol levels, unless there is a contraindication.

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References

  1. Fox KF, Cowie MR, Wood DA, et al. Coronary artery disease as the cause of incident heart failure in the population. Eur Heart J 2001; 22: 228–36

    Article  PubMed  CAS  Google Scholar 

  2. Berry C, Murdoch DR, McMurray JJ. Economics of chronic heart failure. Eur J Heart Fail 2001; 3: 283–91

    Article  PubMed  CAS  Google Scholar 

  3. Stewart S, MacIntyre K, MacLeod MM, et al. Trends in hospitalization for heart failure in Scotland, 1990–1996: an epidemic that has reached its peak? Eur Heart J 2001; 22: 209–17

    Article  PubMed  CAS  Google Scholar 

  4. Zannad F. Have we jugulated the epidemic of heart failure? One swallow does not make a summer. Eur Heart J 2001; 22: 188–90

    Article  PubMed  CAS  Google Scholar 

  5. Cleland JG, Khand A, Clark A. The heart failure epidemic: exactly how big is it? Eur Heart J 2001; 22: 623–6

    Article  PubMed  CAS  Google Scholar 

  6. Hedberg P, Lonnberg I, Jonason T, et al. Left ventricular systolic dysfunction in 75-year-old men and women: a population-based study. Eur Heart J 2001; 22: 676–83

    Article  PubMed  CAS  Google Scholar 

  7. Diabetes Statistics. National Diabetes Information Clearinghouse. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 1999: NIH publication 99-3926

  8. Burke JP, Williams K, Gaskill SP, et al. Rapid rise in the incidence of type 2 diabetes from 1987 to 1996: results from the San Antonio Heart Study. Arch Intern Med 1999; 159: 1450–6

    Article  PubMed  CAS  Google Scholar 

  9. Grundy SM, Benjamin IJ, Burke GL, et al. Diabetes and cardiovascular disease: a statement for healthcare professionals from the American Heart Association. Circulation 1999; 100: 1134–46

    Article  PubMed  CAS  Google Scholar 

  10. Mokdad AH, Ford ES, Bowman BA, et al. The continuing increase of diabetes in the US. Diabetes Care 2001; 24: 412

    Article  PubMed  CAS  Google Scholar 

  11. Drivsholm T, Ibsen H, Schroll M, et al. Increasing prevalence of diabetes mellitus and impaired glucose tolerance among 60-year-old Danes. Diabet Med 2000; 18: 126–32

    Article  Google Scholar 

  12. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999; 281: 1291–7

    Article  PubMed  CAS  Google Scholar 

  13. 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 

  14. He J, Ogden LG, Bazzano LA, et al. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001; 161: 996–1002

    Article  PubMed  CAS  Google Scholar 

  15. Shehadeh A, Regan TJ. Cardiac consequences of diabetes mellitus. Clin Cardiol 1995; 18: 301–5

    Article  PubMed  CAS  Google Scholar 

  16. Nichols GA, Hillier TA, Erbey JR, et al. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001; 24: 1614–19

    Article  PubMed  CAS  Google Scholar 

  17. Gottdiener JS, Arnold AM, Aurigemma GP, et al. Predictors of congestive heart failure in the elderly: the Cardiovascular Health Study. J Am Coll Cardiol 2000; 35: 1628–37

    Article  PubMed  CAS  Google Scholar 

  18. Fisman EZ, Motro M, Tenenbaum A, et al. Impaired fasting glucose concentrations in nondiabetic patients with ischemic heart disease: a marker for a worse prognosis. Am Heart J 2001; 141: 485–90

    Article  PubMed  CAS  Google Scholar 

  19. Jarrett RJ, Shipley MJ. Type 2 (non-insulin-dependent diabetes) and cardiovascular disease: putative association via common antecedents. Further evidence from the Whitehall study. Diabetologia 1988; 31: 737–40

    Article  PubMed  CAS  Google Scholar 

  20. Swan JW, Walton C, Godsland IF, et al. Insulin resistance in chronic heart failure. Eur Heart J 1994; 15: 1528–32

    PubMed  CAS  Google Scholar 

  21. Swan JW, Anker SD, Walton C, et al. Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. J Am Coll Cardiol 1997; 30: 527–32

    Article  PubMed  CAS  Google Scholar 

  22. American Diabetes Association. Report of the expert committees on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183–97

    Google Scholar 

  23. Tenenbaum A, Motro M, Fisman EZ, et al. Status of glucose metabolism in patients with heart failure secondary to coronary artery disease. Am J Cardiol 2002 Sep; 90(5): 529–32

    Article  PubMed  CAS  Google Scholar 

  24. The DECODE study group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999; 354: 617–21

    Article  Google Scholar 

  25. Lillioja S, Mott DM, Spraul M, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus: prospective studies of Pima Indians. N Engl J Med 1993; 329: 1988–92

    Article  PubMed  CAS  Google Scholar 

  26. Laws A, Reaven GM. Insulin resistance and risk factors for coronary heart disease. Baillieres Clin Endocrinol Metab 1993; 7: 1063–78

    Article  PubMed  CAS  Google Scholar 

  27. Solang L, Malmberg K, Ryden L. Diabetes mellitus and congestive heart failure: further knowledge needed. Eur Heart J 1999; 20: 789–95

    Article  PubMed  CAS  Google Scholar 

  28. 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: 1368–75

    Article  PubMed  CAS  Google Scholar 

  29. Reis SE, Holubkov R, Edmundowicz D, et al. Treatment of patients admitted to the hospital with congestive heart failure: specialty-related disparities in practice patterns and outcomes. J Am Coll Cardiol 1997; 30: 733–8

    Article  PubMed  CAS  Google Scholar 

  30. Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham study. JAMA 1979; 241: 2035–8

    Article  PubMed  CAS  Google Scholar 

  31. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients with diabetes. Circulation 2001; 103: 2668–73

    Article  PubMed  CAS  Google Scholar 

  32. 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: 1017–20

    Article  PubMed  CAS  Google Scholar 

  33. 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: 421–8

    Article  PubMed  CAS  Google Scholar 

  34. 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 

  35. Malmberg K, Yusuf S, Gerstein HC, et al. 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 2000; 102: 1014–9

    Article  PubMed  CAS  Google Scholar 

  36. Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes. Part I: general concepts. Circulation 2002; 105: 1727–33

    Article  PubMed  CAS  Google Scholar 

  37. Dei Cas L, Buia E, Manca C, et al. Il cuore nel diabetico. Recenti Prog Med 1983; 74: 53–64

    PubMed  CAS  Google Scholar 

  38. Devereux RB, Roman MJ, Paranicas M, et al. Impact of diabetes on cardiac structure and function: the Strong Heart Study. Circulation 2000; 101: 2271–6

    Article  PubMed  CAS  Google Scholar 

  39. Mizushige K, Yao L, Noma T, 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: 899–907

    Article  PubMed  CAS  Google Scholar 

  40. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 1998; 317: 703–13

    Article  Google Scholar 

  41. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000; 342: 145–53

    Article  PubMed  CAS  Google Scholar 

  42. Dagenais GR, Yusuf S, Bourassa MG, et al. Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study. Circulation 2001; 104: 522–6

    Article  PubMed  CAS  Google Scholar 

  43. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. Circulation 2001; 104: 2996–3007

    Article  PubMed  CAS  Google Scholar 

  44. Burchfiel CM, Curb JD, Rodriguez BL, et al. Incidence and predictors of diabetes in Japanese-American men: the Honolulu Heart Program. Ann Epidemiol 1995; 5: 33–43

    Article  PubMed  CAS  Google Scholar 

  45. von Eckardstein A, Schulte H, Assmann G. Risk for diabetes mellitus in middle-aged Caucasian male participants of the PROCAM study: implications for the definition of impaired fasting glucose by the American Diabetes Association. Prospective Cardiovascular Munster. J Clin Endocrinol Metab 2000; 85: 3101–8

    Article  Google Scholar 

  46. Mykkanen L, Kuusisto J, Pyorala K, et al. Disease risk factors as predictors of type 2 (non-insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 1993; 36: 553–9

    Article  PubMed  CAS  Google Scholar 

  47. Moore LL, Visioni AJ, Wilson PW, et al. Can sustained weight loss in overweight individuals reduce the risk of diabetes mellitus? Epidemiology 2000; 11: 269–73

    Article  PubMed  CAS  Google Scholar 

  48. Vanderpump MP, Tunbridge WM, French JM, et al. The incidence of diabetes mellitus in an English community: a 20-year follow-up of the Whickham Survey. Diabet Med 1996; 13: 741–7

    Article  PubMed  CAS  Google Scholar 

  49. Perry IJ, Wannamethee SG, Walker MK, et al. Prospective study of risk factors for development of non-insulin dependent diabetes in middle aged British men. BMJ 1995; 310: 560–4

    Article  PubMed  CAS  Google Scholar 

  50. Fonseca VA. Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease. Am J Cardiol 2003; 92(4A): 50J–60J

    Article  PubMed  Google Scholar 

  51. Parsonage W, Hetmanski D, Cowley A. Differentiation of the metabolic and vascular effects of insulin in insulin resistance in patients with chronic heart failure. Am J Cardiol 2002; 89: 696–703

    Article  PubMed  CAS  Google Scholar 

  52. Coats AJ, Anker SD, Anker S. Insulin resistance in chronic heart failure. J Cardiovasc Pharmacol 2000; 35 (7 Suppl. 4): S9–14

    Article  PubMed  CAS  Google Scholar 

  53. Helmrich SP, Ragland DR, Leung RW, et al. Physical activity and reduced occurrence of non-insulin dependent diabetes mellitus. N Engl J Med 1991; 325: 147–52

    Article  PubMed  CAS  Google Scholar 

  54. Manson JE, Rimm EB, Stampfer MJ, et al. Physical activity and incidence of non-insulin dependent diabetes in women. Lancet 1991; 338: 774–8

    Article  PubMed  CAS  Google Scholar 

  55. Candido R, Srivastava P, Cooper ME, et al. Diabetes mellitus: a cardiovascular disease. Curr Opin Investig Drugs 2003; 4: 1088–94

    PubMed  Google Scholar 

  56. Grundy SM. Higher incidence of new-onset diabetes in patients with heart failure. Am J Med 2003; 114: 331–2

    Article  PubMed  Google Scholar 

  57. Omran AR. The epidemiologic transition: a theory of the epidemiology of population change. Milbank Mem Fund Q 1971; 49: 509–38

    Article  PubMed  CAS  Google Scholar 

  58. LaPorte RE. How to improve monitoring and forecasting of disease patterns. BMJ 1993; 307: 1573–4

    Article  PubMed  CAS  Google Scholar 

  59. 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: 213–8

    PubMed  CAS  Google Scholar 

  60. 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: 271–5

    Article  PubMed  Google Scholar 

  61. Auwerx J. PPAR gamma, the ultimate thrifty gene. Diabetologia 1999; 42: 1033–49

    Article  PubMed  CAS  Google Scholar 

  62. Vamecq J, Latruffe N. Medical significance of peroxisome proliferator-activated receptors. Lancet 1999; 354: 141–8

    Article  PubMed  CAS  Google Scholar 

  63. Hayden MR, Tyagi SC. Intimai redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy. Cardiovasc Diabetol 2002; 1(1): 3

    Article  PubMed  Google Scholar 

  64. Porte Jr D, Kahn SE. Beta-cell dysfunction and failure in type 2 diabetes: potential mechanisms. Diabetes 2001; 50 Suppl. 1: S160–3

    Article  PubMed  CAS  Google Scholar 

  65. Tenenbaum A, Fisman EZ, Motro M. Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). Cardiovasc Diabetol 2003; 2(1): 4

    Article  PubMed  Google Scholar 

  66. Anker SD, Sharma R. The syndrome of cardiac cachexia. Int J Cardiol 2002; 85: 51–66

    Article  PubMed  Google Scholar 

  67. Toth MJ, Gottlieb SS, Fisher ML, et al. Plasma leptin concentrations and energy expenditure in heart failure patients. Metabolism 1997; 46: 450–3

    Article  PubMed  CAS  Google Scholar 

  68. Toth MJ, Gottlieb SS, Fisher ML, et al. Skeletal muscle atrophy and peak oxygen consumption in heart failure. Am J Cardiol 1997; 79: 1267–9

    Article  PubMed  CAS  Google Scholar 

  69. Conraads VM, Bosnians JM, Vrints CJ. Chronic heart failure: an example of a systemic chronic inflammatory disease resulting in cachexia. Int J Cardiol 2002; 85: 33–49

    Article  PubMed  Google Scholar 

  70. Tracey KJ, Cerami A. Metabolic responses to cachectin/TNF. A brief review. Ann N Y Acad Sci 1990; 597: 325–31

    Google Scholar 

  71. Eichhorn EJ, Bristow MR. Medical therapy can improve the biological properties of the chronically failing heart: a new era in the treatment of heart failure. Circulation 1996; 94: 2285–96

    Article  PubMed  CAS  Google Scholar 

  72. Diebert DC, DeFronzo RA. Epinephrine-induced insulin resistance in man. J Clin Invest 1980; 65: 717–21

    Article  Google Scholar 

  73. Rizza RA, Cryer PE, Haymond MW, et al. Adrenergic mechanisms for the effect of epinephrine on glucose production and clearance in man. J Clin Invest 1980; 65: 682–9

    Article  PubMed  CAS  Google Scholar 

  74. Bauters C, Lamblin N, McFadden EP, et al. Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol 2003; 2: 1

    Article  PubMed  Google Scholar 

  75. Perin PC, Maule S, Quadri R. Sympathetic nervous system, diabetes, and hypertension. Clin Exp Hypertens 2001; 23: 45–55

    Article  PubMed  CAS  Google Scholar 

  76. Doehner W, Rauchhaus M, Godsland IF, et al. Insulin resistance in moderate chronic heart failure is related to hyperleptinaemia, but not to norepinephrine or TNF-α. Int J Cardiol 2002; 83: 73–81

    Article  PubMed  Google Scholar 

  77. Murdoch DR, Rooney E, Dargie HJ, et al. Inappropriately low plasma leptin concentration in the cachexia associated with chronic heart failure. Heart 1999; 82: 352–6

    PubMed  CAS  Google Scholar 

  78. Fisman EZ, Tenenbaum A, Motro M. Cardiovascular diabetology in the core of a novel interleukins classification: the bad, the good and the aloof. Cardiovasc Diabetol 2003; 2: 11

    Article  PubMed  Google Scholar 

  79. Paolisso G, Tagliamonte MR, Rizzo MR, et al. Prognostic importance of insulin-mediated glucose uptake in aged patients with congestive heart failure secondary to mitral and/or aortic valve disease. Am J Cardiol 1999; 83: 1338–44

    Article  PubMed  CAS  Google Scholar 

  80. Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403

    Article  PubMed  CAS  Google Scholar 

  81. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance: the Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537–44

    Article  PubMed  CAS  Google Scholar 

  82. Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001; 344: 1343–50

    Article  PubMed  CAS  Google Scholar 

  83. Chiasson JL, Josse RG, Gomis R, et al. STOP-NIDDM Trail Research Group. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359: 2072–7

    Article  PubMed  CAS  Google Scholar 

  84. Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med 2000; 160: 1321–6

    Article  PubMed  CAS  Google Scholar 

  85. Yusuf S, Gerstein H, Hoogwerf B, et al. HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001; 286: 1882–5

    Article  PubMed  CAS  Google Scholar 

  86. Tenenbaum A, Motro M, Fisman EZ, et al. Peroxisome proliferator-activated receptors ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation 2004; 109: 2197–202

    Article  PubMed  CAS  Google Scholar 

  87. Feskens EJ, Kromhout D. Cardiovascular risk factors and the 25-year incidence of diabetes mellitus in middle-aged men. The Zutphen Study. Am J Epidemiol 1989; 130: 1101–8

    PubMed  CAS  Google Scholar 

  88. Rimm EB, Chan J, Stampfer MJ, et al. Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men. BMJ 1995; 310: 555–9

    Article  PubMed  CAS  Google Scholar 

  89. Uchimoto S, Tsumura K, Hayashi T, et al. Impact of cigarette smoking on the incidence of type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Heart Survey. Diabet Med 1999; 16: 951–5

    Article  PubMed  CAS  Google Scholar 

  90. Sowers JR, Epstein M. Diabetes mellitus and associated hypertension, vascular disease and nephropathy: an update. Hypertension 1995; 26 (Pt 1): 869–79

    Article  PubMed  CAS  Google Scholar 

  91. Wang S-L, Head J, Stevens L, et al. Excess mortality and its relation to hypertension and proteinuria in diabetic patients: the World Health Association Multinational Study of Vascular Disease in Diabetes. Diabetes Care 1996; 19: 305–12

    Article  PubMed  CAS  Google Scholar 

  92. Sowers JR. Recommendations for special populations: diabetes mellitus and the metabolic syndrome. Am J Hypertens 2003; 16: 41–5

    Article  Google Scholar 

  93. American Diabetes Association. Standards of medical care for patients with diabetes mellitus (position statement). Diabetes Care 2001; 24 Suppl. 1: S33–43

    Article  Google Scholar 

  94. Laakso M. Benefits of strict glucose and blood pressure control in type 2 diabetes: lessons from the UK Prospective Diabetes Study. Circulation 1999; 99: 461–2

    Article  PubMed  CAS  Google Scholar 

  95. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet 2000; 355: 253–9

    Article  Google Scholar 

  96. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 1755–62

    Article  PubMed  CAS  Google Scholar 

  97. Staessen JA, Thijs L, Gasowski J, et al. Treatment of isolated systolic hypertension in the elderly: further evidence from the systolic hypertension in Europe (Syst-Eur) trial. Am J Cardiol 1998; 82: 20R–2R

    Article  PubMed  CAS  Google Scholar 

  98. Sowers JR, Epstein M, Frolich ED. Diabetes, hypertension and cardiovascular disease. Hypertension 2001; 37: 1053–9

    Article  PubMed  CAS  Google Scholar 

  99. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care 1998; 21: 597–603

    Article  PubMed  CAS  Google Scholar 

  100. Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999; 353: 611–6

    Article  PubMed  CAS  Google Scholar 

  101. Lindholm LH. The outcome of STOP-Hypertension-2 in relation to the 1999 WHO/ISH hypertension guidelines. Blood Press Suppl 2000; 2: 21–4

    PubMed  CAS  Google Scholar 

  102. Estacio RO, Jeffers W, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med 1998; 338: 645–52

    Article  PubMed  CAS  Google Scholar 

  103. Pahor M, Psaty BM, Alderman MH, et al. Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. Diabetes Care 2000; 23: 888–92

    Article  PubMed  CAS  Google Scholar 

  104. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–60

    Article  PubMed  CAS  Google Scholar 

  105. Lindholm LH, Dahlöf B, Devereux RB, et al. 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 2002; 359: 995–1010

    Article  PubMed  Google Scholar 

  106. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9

    Article  PubMed  CAS  Google Scholar 

  107. Fisman EZ, Tenenbaum A, Motro M. Losartan and diabetic nephropathy: commentaries on the RENAAL study. Cardiovasc Diabetol 2002; 1: 2

    Article  PubMed  Google Scholar 

  108. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003; 289: 2560–72

    Article  PubMed  CAS  Google Scholar 

  109. Fagot-Campagna A, Rolka DB, Beckles GLA, et al. Prevalence of lipid abnormalities, awareness, and treatment in US adults with diabetes. Diabetes 2000; 49 Suppl. 1: A78–79

    Google Scholar 

  110. Pearson TA, Laurora I, Chu H, et al. The lipid treatment assessment project (LTAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med 2000; 160: 459–67

    Article  PubMed  CAS  Google Scholar 

  111. Multiple Risk Factor Intervention Trial Research Group. Multiple Risk Factor Intervention Trial: risk factor changes and mortality. JAMA 1982; 248: 1465–77

    Article  Google Scholar 

  112. Lamarche B, Tchernof A, Moorjani S, et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study. Circulation 1997; 95: 69–75

    Article  PubMed  CAS  Google Scholar 

  113. Henry RR. Preventing cardiovascular complications of type 2 diabetes: focus on lipid management. Clin Diabetes 2001; 19: 113–20

    Article  Google Scholar 

  114. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1988; 279: 1615–22

    Article  Google Scholar 

  115. Pyorala K, Pedersen TR, Kjekshus J, et al. 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 1997; 20: 614–20

    Article  PubMed  CAS  Google Scholar 

  116. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol: Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410–8

    Article  PubMed  CAS  Google Scholar 

  117. Elkeles RS, Diamond JR, Poulter C, et al. Cardiovascular outcomes in type 2 diabetes: a double-blind placebo-controlled study of bezafibrate: the St. Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. Diabetes Care 1998; 21: 641–8

    Article  PubMed  CAS  Google Scholar 

  118. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med 1999; 159: 2661–7

    Article  PubMed  CAS  Google Scholar 

  119. Tan KCB, Chow WS, Tarn SCF, et al. Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. J Clin Endocrinol Metab 2002; 87: 563–8

    Article  PubMed  CAS  Google Scholar 

  120. American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care 2000; 24 Suppl. 1: S557–60

    Google Scholar 

  121. Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110: 227–39

    Article  PubMed  Google Scholar 

  122. MRC/BCHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 2005–16

    Article  CAS  Google Scholar 

  123. Genest Jr JJ, McNamara JR, Salem DN, et al. Plasma homocysteine levels in men with premature coronary artery disease. J Am Coll Cardiol 1990; 16: 1114–9

    Article  PubMed  Google Scholar 

  124. Wald NJ, Watt HC, Law MR, et al. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998; 158: 862–7

    Article  PubMed  CAS  Google Scholar 

  125. Okada E, Oida K, Tada H, et al. Hyperhomocysteinemia is a risk factor for coronary arteriosclerosis in Japanese patients with type 2 diabetes. Diabetes Care 1999; 22: 484–90

    Article  PubMed  CAS  Google Scholar 

  126. Smulders YM, Rakic M, Slaats EH, et al. Fasting and post-methionine homocysteine levels in NIDDM: determinants and correlations with retinopathy, albuminuria, and cardiovascular disease. Diabetes Care 1999; 22: 125–32

    Article  PubMed  CAS  Google Scholar 

  127. Hoogeveen EK, Kostense PJ, Jakobs C, et al. Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes: 5-year follow-up of the Hoorn Study. Circulation 2000; 101: 1506–11

    Article  PubMed  CAS  Google Scholar 

  128. Eikelboom JW, Lonn E, Genest J, et al. Homocysteine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med 1999; 131: 363–75

    PubMed  CAS  Google Scholar 

  129. Liem A, Reynierse-Buitenwerf GH, Zwinderman AH, et al. Secondary prevention with folic acid: effects on clinical outcomes. J Am Coll Cardiol 2003; 41: 2105–13

    Article  PubMed  CAS  Google Scholar 

  130. Davi G, Catalano I, Averna M. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med 1990; 322: 1769–74

    Article  PubMed  CAS  Google Scholar 

  131. Patrono C. Aspirin as an antiplatelet drug. N Engl J Med 1994; 330: 1287–94

    Article  PubMed  CAS  Google Scholar 

  132. Patrono C, Ciabattoni G, Patrignani P, et al. Clinical pharmacology of platelet cyclo-oxygenase inhibition. Circulation 1985; 72: 1177–84

    Article  PubMed  CAS  Google Scholar 

  133. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ 1994; 308: 81–106

    Article  Google Scholar 

  134. Anonymous. Aspirin therapy in diabetes. American Diabetes Association. Diabetes Care 1997; 20: 1772–3

    Google Scholar 

  135. Rolka DB, Fagot-Campagna A, Narayan KM. Aspirin use among adults with diabetes: estimates from the Third National Health and Nutrition Examination Survey. Diabetes Care 2001; 24: 197–201

    Article  PubMed  CAS  Google Scholar 

  136. Aronson D, Mittleman MA, Burger AJ. Effects of sulfonylurea hypoglycemic agents and adenosine triphosphate dependent potassium channel antagonists on ventricular arrhythmias in patients with decompensated heart failure. Pacing Clin Electrophysiol 2003 May; 26(5): 1254–61

    Article  PubMed  Google Scholar 

  137. DeFronzo RA. Pharmacologie therapy for type 2 diabetes. Ann Intern Med 1999; 131: 281–303

    PubMed  CAS  Google Scholar 

  138. Misbin RI, Green L, Stadel BV, et al. Lactic acidosis in patients with diabetes treated with metformin. N Engl J Med 1998 Jan 22; 338(4): 265–6

    Article  PubMed  CAS  Google Scholar 

  139. Rachmani R, Slavachevski I, Levi Z, et al. Metformin in patients with type 2 diabetes mellitus: reconsideration of traditional contraindications. Eur J Intern Med 2002 Oct; 13(7): 428–33

    Article  PubMed  CAS  Google Scholar 

  140. Ben-Ami H, Krivoy N, Nagachandran P, et al. An interaction between digoxin and acarbose. Diabetes Care 1999 May; 22(5): 860–1

    Article  PubMed  CAS  Google Scholar 

  141. Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996; 45: 1661–9

    Article  PubMed  CAS  Google Scholar 

  142. Wang CH, Weisel RD, Liu PP, et al. Glitazones and heart failure: critical appraisal for the clinician. Circulation 2003; 107: 1350–4

    Article  PubMed  Google Scholar 

  143. Ghazzi MN, Perez JE, Antonucci TK, et al. Cardiac and glycemic benefits of troglitazone treatment in NIDDM: the Troglitazone Study Group. Diabetes 1997; 46: 433–9

    Article  PubMed  CAS  Google Scholar 

  144. Dahlof B, Pennert K, Hansson L. Reversal of left ventricular hypertrophy in hypertensive patients: a metaanalysis of 109 treatment studies. Am J Hypertens 1992; 5: 95–110

    PubMed  CAS  Google Scholar 

  145. Asakawa M, Takano H, Nagai T, et al. Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation 2002; 105: 1240–6

    Article  PubMed  CAS  Google Scholar 

  146. Mudaliar S, Henry RR. New oral therapies for type 2 diabetes mellitus: the glitazones or insulin sensitizers. Annu Rev Med 2001; 52: 239–57

    Article  PubMed  CAS  Google Scholar 

  147. Hattori Y, Akimoto K, Kasai K. The effects of thiazolidinediones on vascular smooth muscle cell activation by angiotensin II. Biochem Biophys Res Commun 2000; 273: 1144–9

    Article  PubMed  CAS  Google Scholar 

  148. Bryant D, Becker L, Richardson J, et al. Cardiac failure in transgenic mice with myocardial expression of tumor necrosis factor-α. Circulation 1998; 97: 1375–81

    Article  PubMed  CAS  Google Scholar 

  149. Wayman NS, Hattori Y, McDonald MC, et al. Ligands of the peroxisome proliferator-activated receptors (PPAR-χ and PPAR-α) reduce myocardial infarct size. FASEB J 2002; 16: 1027–40

    Article  PubMed  CAS  Google Scholar 

  150. Rodrigues B, Cam MC, McNeill JH. Metabolic disturbances in diabetic cardiomyopathy. Mol Cell Biochem 1998; 180: 53–7

    Article  PubMed  CAS  Google Scholar 

  151. Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation 2002 Aug 6; 106(6): 679–84

    Article  PubMed  CAS  Google Scholar 

  152. Kermani A, Garg A. Thiazolidinedione-associated congestive heart failure and pulmonary edema. Mayo Clin Proc 2003 Sep; 78(9): 1088–91

    Article  PubMed  CAS  Google Scholar 

  153. Thomas ML, Lloyd SJ. Pulmonary edema associated with rosiglitazone and troglitazone. Ann Pharmacother 2001; 35: 123–4

    Article  PubMed  CAS  Google Scholar 

  154. Wooltorton E. Rosiglitazone (Avandia), and pioglitazone (Actos), and heart failure. CMAJ 2002 Jan; 166(2): 219

    PubMed  Google Scholar 

  155. Hirsch IB, Kelly J, Cooper S. Pulmonary edema associated with troglitazone therapy [letter]. Arch Intern Med 1999; 159(15): 1811

    Article  PubMed  CAS  Google Scholar 

  156. Niemeyer NV, Janney LM. Thiazolidinedione-induced edema. Pharmacotherapy 2002; 22: 924–9

    Article  PubMed  Google Scholar 

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  1. Cardiac Rehabilitation Institute, Sheba Medical Center, 52621, Tel-Hashomer, Israel

    Alexander Tenenbaum & Enrique Z. Fisman

  2. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Alexander Tenenbaum & Enrique Z. Fisman

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  1. Alexander Tenenbaum
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Tenenbaum, A., Fisman, E.Z. Impaired Glucose Metabolism in Patients with Heart Failure. Am J Cordiovosc Drugs 4, 269–280 (2004). https://doi.org/10.2165/00129784-200404050-00001

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