on August 13, 2007
Published online before print August 13, 2007, doi: 10.1161/CIRCULATIONAHA.106.645614
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Submitted on July 19, 2006
From the Department of Internal Medicine, Divisions of Hypertension (J.M.M., N.S., R.G.V., L.S.S.) and Endocrinology (I.L., I.Z., P.R.), Touchstone Center for Diabetes Research (R.U.), and the Department of Radiology (T.T., L.S.S.), University of Texas Southwestern Medical Center; Veterans Affairs Medical Center (R.U.); and Institute for Exercise and Environmental Medicine (B.D.L.), Presbyterian Hospital; all in Dallas, Tex. * To whom correspondence should be addressed. E-mail: lidia.szczepaniak{at}utsouthwestern.edu.
Background—The risk of heart failure in type 2 diabetes mellitus is greater than can be accounted for by hypertension and coronary artery disease. Rodent studies indicate that in obesity and type 2 diabetes mellitus, lipid overstorage in cardiac myocytes produces lipotoxic intermediates that cause apoptosis, which leads to heart failure. In humans with diabetes mellitus, cardiac steatosis previously has been demonstrated in explanted hearts of patients with end-stage nonischemic cardiomyopathy. Whether cardiac steatosis precedes the onset of cardiomyopathy in individuals with impaired glucose tolerance or in patients with type 2 diabetes mellitus is unknown. Methods and Results—To represent the progressive stages in the natural history of type 2 diabetes mellitus, we stratified 134 individuals (age 45±12 years) into 1 of 4 groups: (1) lean normoglycemic (lean), (2) overweight and obese normoglycemic (obese), (3) impaired glucose tolerance, and (4) type 2 diabetes mellitus. Localized 1H magnetic resonance spectroscopy and cardiac magnetic resonance imaging were used to quantify myocardial triglyceride content and left ventricular function, respectively. Compared with lean subjects, myocardial triglyceride content was 2.3-fold higher in those with impaired glucose tolerance and 2.1-fold higher in those with type 2 diabetes mellitus (P<0.05). Left ventricular ejection fraction was normal and comparable across all groups. Conclusions—In humans, impaired glucose tolerance is accompanied by cardiac steatosis, which precedes the onset of type 2 diabetes mellitus and left ventricular systolic dysfunction. Thus, lipid overstorage in human cardiac myocytes is an early manifestation in the pathogenesis of type 2 diabetes mellitus and is evident in the absence of heart failure.
Accepted on June 15, 2007
Cardiac Steatosis in Diabetes Mellitus. A 1H-Magnetic Resonance Spectroscopy Study
Jonathan M. McGavock PhD,
Key words: magnetic resonance spectroscopy • obesity • metabolism
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