Abstract
Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an α-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.
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Braunwald E, Bristow MR : Congestive heart failure: fifty years of progress. Circulation 2000; 102: 14–23.
Torre-Amione G : The syndrome of heart failure: emerging concepts in the understanding of its pathogenesis and treatment. Curr Opin Cardiol 1999; 14: 193–195.
Packer M : Neurohormonal interactions and adaptations in congestive heart failure. Circulation 1988; 77: 721–730.
Drexler H, Hornig B : Importance of endothelial function in chronic heart failure. J Cardiovasc Pharmacol 1996; 27: S9–S12.
Levine TB, Francis GS, Goldsmith SR, et al: Activity of the sympathetic nervous system and renin-angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure. Am J Cardiol 1982; 49: 885–891.
Marangou AG, Alford FP, Ward G, et al: Hormonal effects of norepinephrine on acute glucose disposal in humans: a minimal model analysis. Metabolism 1988; 37: 885–891.
Juan CC, Chien Y, Wu LY, et al: Angiotensin II enhances insulin sensitivity in vitro and in vivo. Endocrinology 2005; 146: 2246–2254.
Risso A, Mercuri F, Quagliaro L, et al: Intermittent high glucose enhances apoptosis in human umbilical vein endothelial cells in culture. Am J Physiol 2001; 281: E924–E930.
Quagliaro L, Piconi L, Assaloni R, et al: Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 2003; 52: 2795–2804.
Baumgartner-Parzer SM, Wagner L, Pettermann M, et al: High-glucose–triggered apoptosis in cultured endothelial cells. Diabetes 1995; 44: 1323–1327.
Neri S, Signorelli SS, Torrisi B, et al: Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls. Clin Ther 2005; 27: 1764–1773.
Mykkanen L, Kuusisto J, Pyorala K, et al: Cardiovascular disease risk factors as predictors of type 2 (non–insulin-dependent) diabetes mellitus in elderly subjects. Diabetologia 1993; 36: 553–559.
Swan JW, Walton C, Godsland IF, et al: Insulin resistance in chronic heart failure. Eur Heart J 1994; 15: 1528–1532.
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: 527–532.
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.
Wisniacki N, Taylor W, Lye M, Wilding JP : Insulin resistance and inflammatory activation in older patients with systolic and diastolic heart failure. Heart 2005; 91: 32–37.
Nielson C, Lange T : Blood glucose and heart failure in nondiabetic patients. Diabetes Care 2005; 28: 607–611.
He J, Ogden LG, Bazzano LA, et al: Risk factors for congestive heart failure in US men and women: NHANESI epidemiologic follow-up study. Arch Intern Med 2001; 161: 996–1002.
Shehadeh A, Regan TJ : Cardiac consequences of diabetes mellitus. Clin Cardiol 1995; 18: 301–305.
Kostis JB, Sanders M : The association of heart failure with insulin resistance and the development of type 2 diabetes. Am J Hypertens 2005; 18: 731–737.
Amato L, Paolisso G, Cacciatore F, et al, The Osservatorio Geriatrico Regione Campania Group: Congestive heart failure predicts the development of non–insulin-dependent diabetes mellitus in the elderly. Diabetes Metab 1997; 23: 213–218.
Norhammar A, Malmberg K : Heart failure and glucose abnormalities: an increasing combination with poor functional capacity and outcome. Eur Heart J 2000; 21: 1293–1294.
American Diabetes Association : Report of the expert committees on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 29: 1183–1197.
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: 617–621.
Steel RGD, Torrie JH : Principles and Procedures of Statistics. A Biomedical Approach, 2nd ed. New York, McGraw-Hill Publishing Co, 1980, pp 137–238.
Tenenbaum A, Fisman EZ, Boyko V, et al: Hypertension in diet versus pharmacologically treated diabetics: mortality over a 5-year follow-up. Hypertension 1999; 33: 1002–1007.
Balkau B, Shipley M, Jarrett RJ, et al: High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care 1998; 21: 360–367.
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: 485–490.
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: 1988–1992.
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: 147–152.
Murray AJ, Anderson RE, Watson GC, et al: Uncoupling proteins in human heart. Lancet 2004; 364: 1786–1788.
Wang XP, Zhang R, Wu K, et al: Angiotensin II mediates acinar cell apoptosis during the development of rat pancreatic fibrosis by AT1R. Pancreas 2004; 29: 264–270.
Scognamiglio R, Negut C, De Kreutzenberg SV, et al: Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 2005; 112: 179–184.
Minamino T, Kitakaze M : Investigation of cellular mechanisms for the treatment of chronic heart failure: insight to nitric oxide− and adenosine-dependent pathways. Expert Opin Invest Drugs 2002; 7: 99–110.
Sanada S, Node K, Asanuma H, et al: Opening of ATP-sensitive potassium channel attenuates cardiac remodeling induced by chronic inhibition of nitric oxide synthesis—role of 70 kDa S6 kinase and extracellular signal–regulated kinase —. J Am Coll Cardiol 2002; 40: 991–997.
Hirooka Y, Eshima K, Setoguchi S, Kishi T, Egashira K, Takeshita A : Vitamin C improves attenuated angiotensin II–induced endothelium-dependent vasodilation in human forearm vessels. Hypertens Res 2003; 26: 953–959.
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Kim, J., Nakatani, S., Hashimura, K. et al. Abnormal Glucose Tolerance Contributes to the Progression of Chronic Heart Failure in Patients with Dilated Cardiomyopathy. Hypertens Res 29, 775–782 (2006). https://doi.org/10.1291/hypres.29.775
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DOI: https://doi.org/10.1291/hypres.29.775
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