Functional class in patients with heart failure is associated with the development of diabetes

CORRESPONDENCE FUNCTIONAL CLASS IN PATIENTS WITH HEART FAILURE IS ASSOCIATED WITH THE DEVELOPMENT OF DIABETES To the Editor: Tenenbaum et al (1) showed that patients with advanced heart failure have a higher incidence of diabetes compared with those with lower functional classes of heart failure. The authors speculate that heart failure– induced diabetes is due to an increase in insulin resistance and a lack of exercise because of the cardiac condition. In an accompanying editorial (2) Grundy postulates that both insulin resistance and decreased insulin secretion are associated with the severity of heart failure. He also speculates that heart failure patients are more obese and have a decreased muscle mass leading to insulin resistance, and that insulin resistance is further increased with hypoperfusion of organs, increased leptin levels, and increased levels of inflammatory cytokines, particularly tumor necrosis factor ␣. Both Tenenbaum et al and Grundy are missing the probable cause of the increased incidence of diabetes. Impaired myocardial performance results in activation of the neurohormonal compensating systems, including activation of the sympathetic nervous system to avoid systemic hypoperfusion, with the degree of sympathetic activation being proportional to the severity of ventricular dysfunction and functional class of heart failure (3). Activation of the sympathetic system not only increases insulin resistance but also decreases the release of insulin from the pancreatic beta cells, increases hepatic glucose production by stimulating both gluconeogenesis and glycogenolysis, and increases glucagon production and lipolysis (4,5). Therefore, higher catecholamine levels are the most likely reason for 412

© 2003 by Excerpta Medica Inc. All rights reserved.

the increased development of diabetes in patients with a lower functional class of heart failure. David S. H. Bell, MB University of Alabama at Birmingham Birmingham, Alabama 1. 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;114:271–75. 2. Grundy SM. Higher incidence of new-onset diabetes in patients with heart failure. Am J Med. 2003;114:331–332. 3. 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;94:2285–2296. 4. Diebert DC, DeFronzo RA. Epinephrineinduced insulin resistance in man. J Clin Invest. 1980;65:717. 5. Rizza RA, Cryer PE, Haymond MW, Gerich JE. Adrenergic mechanisms for the effect of epinephrine on glucose production and clearance in man. J Clin Invest. 1980;65:682.

The Reply: We appreciate the interest of Dr. Bell in our study (1). We concur that impaired myocardial performance results in activation of the neurohormonal compensating systems, including activation of the sympathetic nervous system. As he points out, higher catecholamine level may be one of the reasons for the increased development of diabetes in patients with heart failure. We agree with his statement that activation of the sympathetic system not only increases insulin resistance, but also decreases the release of insulin from the pancreatic beta cells, increases hepatic glucose production by stimulating both gluconeogenesis and glycogenolysis, and increases glucagon production and lipolysis (2,3). However, we do not see any contradiction between our and Dr. Grundy’s (4) positions regarding the importance of lack of physical activity in the increased development of diabetes in patients with heart failure and Dr. Bell’s assertion regarding ac-

tivation of the sympathetic system. Moreover, we have previously reported (5,6) on the beneficial effect of long-term exercise training in reducing catecholamine and atrial natriuretic peptide levels in patients with heart failure. The limited space of the article did not allow us to discuss in depth all possible explanations of the obtained results. We are grateful to Dr. Bell for the opportunity to clarify these points, which provided additional support to our findings. Alexander Tenenbaum, MD Michael Motro, MD Enrique Z. Fisman, MD Chaim Sheba Medical Center Tel-Aviv, Israel 1. 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. 2. Bauters C, Lamblin N, McFadden EP, Van Belle E, Millaire A, De Groote P. Influence of diabetes mellitus on heart failure risk and outcome. Cardiovasc Diabetol. 2003;2:1. 3. Perin PC, Maule S, Quadri R. Sympathetic nervous system, diabetes, and hypertension. Clin Exp Hypertens. 2001;23:45–55. 4. Grundy SM. Higher incidence of new-onset diabetes in patients with heart failure. Am J Med. 2003;114:331–332. 5. Shemesh J, Grossman E, Peleg E, Steinmetz A, Rosenthal T, Motro M. Norepinephrine and atrial natriuretic peptide responses to exercise testing in rehabilitated and nonrehabilitated men with ischemic cardiomyopathy after healing of anterior wall acute myocardial infarction. Am J Cardiol. 1995; 75:1072–1074. 6. Tenenbaum A, Shemesh J, Giannuzzi P, Corra` U. Attenuation of unfavorable sympathetic hyperactivity induced by longterm physical training in postinfarction patients: fact or speculation? Circulation. 1998;98:1042–1043.

IS CHRONIC AUTOIMMUNE THYROIDITIS A SYSTEMIC DISEASE? To the Editor: We read with great interest the paper by Vaglio et al, which reported the occurrence of clinical and biochemical features of autoimmune disorders 0002-9343/03/$–see front matter