CORRESPONDENCE: LETTER TO THE EDITOR
Insulin Resistance in Chronic Heart Failure
Wolfram Doehner, MD, PhD*,
Stephan von Haehling, MD and
Stefan D. Anker, MD, PhD
* Division of Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Medical Center, Augustenburger Platz 1, 13353 Berlin, Germany (Email: wolfram.doehner{at}charite.de).
In their recent study, Witteles and Fowler (1) highlight the impact of insulin-resistant cardiomyopathy on development, clinical severity, and progression of chronic heart failure (CHF). We would like to extend this important perspective on impaired insulin sensitivity in CHF from a mere myocardial view to a generalized aspect within CHF pathophysiology.
It should be noted that insulin resistance observed in epidemiological studies in CHF patients refers always to the whole body rather than to the myocardium alone. Skeletal muscle accounts for the majority of insulin-stimulated glucose uptake (2). Accordingly, most human studies as discussed by the authors assessed insulin resistance (by one way or another) of the whole body, and common mechanisms of impaired glucose utilization in skeletal muscle and myocardium have been adopted. It is not clear whether the insulin resistance of the myocardium has specific characteristics that are different and that should be viewed strictly separated from the skeletal muscle.
Extending the concept of insulin resistance beyond the myocardium and involving whole-body impaired insulin sensitivity will by no means diminish the significance of this impairment in energy metabolism as a strong and independent contributor to CHF morbidity and mortality (3,4). In fact, extending this concept reflects the increasingly appreciated impact of peripheral factors contributing to CHF pathophysiology. In the prolonged course of CHF, (mal)adaptations to impaired perfusion result in intrinsic structural and functional changes in various organs and tissues, such as muscle tissue. This growing influence of the periphery on the symptoms (muscle fatigue, reduced power, dyspnea) and prognosis of CHF are emphasized in the muscle hypothesis (5). Given the strong anabolic function of insulin, impaired global insulin sensitivity may be a vital underlying cause in the overall catabolic/anabolic imbalance in CHF, leading to tissue wasting and, eventually, to cardiac cachexia (6). Moreover, currently discussed therapeutic options to improve the (energy) metabolic efficiency exert systemic effects (i.e., on metabolism in both the myocardium and skeletal muscle).
By extending the view on insulin resistance in CHF to the whole body, pathophysiologic, symptomatic, prognostic, and therapeutic considerations are met more thoroughly.
 |
References
|
|---|
1. Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy: clinical evidence, mechanisms, and treatment options J Am Coll Cardiol 2008;51:93-102.[Abstract/Free Full Text]2. Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy N Engl J Med 1990;322:262-263.[Web of Science][Medline] 3. Doehner W, Pflaum CD, Rauchhaus M, et al. Leptin, insulin sensitivity and growth hormone binding protein in chronic heart failure with and without cardiac cachexia Eur J Endocrinol 2001;145:727-735.[Abstract] 4. Doehner W, Rauchhaus M, Ponikowski P, et al. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure J Am Coll Cardiol 2005;46:1019-1026.[Abstract/Free Full Text] 5. Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: central role of the periphery J Am Coll Cardiol 1996;28:1092-1102.[Abstract] 6. Anker SD, Chua TP, Ponikowski P, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia Circulation 1997;96:526-534.[Abstract/Free Full Text]
Related Article
-
Reply
- Ronald M. Witteles and Michael B. Fowler
J. Am. Coll. Cardiol. 2008 52: 239-240.
[Full Text]
[PDF]
|
Top
References