Altered Myocardial Substrate Metabolism and Decreased Diastolic Function in Nonischemic Human Diabetic Cardiomyopathy: Studies With Cardiac Positron Emission Tomography and Magnetic Resonance Imaging

• Published in: Journal of the American College of Cardiology Vol. 54; no. 16; pp. 1524 - 1532
• Main Authors: RIJZEWIJK, Luuk J, VAN DER MEER, Rutger W, LAMMERTSMA, Adriaan A, SMIT, Johannes W. A, DIAMANT, Michaela, LAMB, Hildo J, DE JONG, Hugo W. A. M, LUBBERINK, Mark, ROMIJN, Johannes A, BAX, Jeroen J, DE ROOS, Albert, TWISK, Jos W, HEINE, Robert J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 13-10-2009; Elsevier Limited
• Subjects: Aged; Biological and medical sciences; Blood pressure; Cardiology; Cardiology. Vascular system; Cardiomyopathies - diagnosis; Cardiomyopathies - etiology; Cardiomyopathies - metabolism; Cardiovascular disease; Chromatography, High Pressure Liquid; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Diastole; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glucose - metabolism; Glycated Hemoglobin A - metabolism; Heart; Heart attacks; Humans; Magnetic Resonance Imaging - methods; Male; Medical sciences; Metabolism; Middle Aged; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Positron-Emission Tomography - methods; Reproducibility of Results; Studies; Ventricular Function, Left - physiology; Endocrinopathy; Radionuclide study; Heart; Human; Cardiac performance; Diastole; Cardiomyopathy; Diabetes mellitus; Cardiovascular disease; Metabolism; Myocardial disease; Nuclear magnetic resonance imaging; Substrate; Heart disease; Myocardium; Medical imagery; Circulatory system; Cardiology; Positron emission tomography; Emission tomography
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2009.04.074

This study was designed to evaluate myocardial substrate and high-energy phosphate (HEP) metabolism in asymptomatic men with well-controlled, uncomplicated type 2 diabetes with verified absence of cardiac ischemia, and age-matched control subjects, and to assess the association with myocardial function.
Metabolic abnormalities, particularly an excessive exposure of the heart to circulating nonesterified fatty acids and myocardial insulin resistance are considered important contributors to diabetic cardiomyopathy in animal models of diabetes. The existence of myocardial metabolic derangements in uncomplicated human type 2 diabetes and their possible contribution to myocardial dysfunction still remain undetermined.
In 78 insulin-naive type 2 diabetes men (age 56.5 +/- 5.6 years, body mass index 28.7 +/- 3.5 kg/m(2), glycosylated hemoglobin A(1c) 7.1 +/- 1.0%; expressed as mean +/- SD) without cardiac ischemia and 24 normoglycemic control subjects (age 54.5 +/- 7.1 years, body mass index 27.0 +/- 2.5 kg/m(2), glycosylated hemoglobin A(1c) 5.3 +/- 0.2%), we assessed myocardial left ventricular (LV) function by magnetic resonance imaging, and myocardial perfusion and substrate metabolism by positron emission tomography using H(2)(15)O, carbon (11)C-palmitate, and 18-fluorodeoxyglucose 2-fluoro-2-deoxy-D-glucose. Cardiac HEP metabolism was assessed by phosphorous P 31 magnetic resonance spectroscopy.
In patients, compared with control subjects, LV diastolic function (E/A ratio: 1.04 +/- 0.25 vs. 1.26 +/- 0.36, p = 0.003) and myocardial glucose uptake (260 +/- 128 nmol/ml/min vs. 348 +/- 154 nmol/ml/min, p = 0.015) were decreased, whereas myocardial nonesterified fatty acid uptake (88 +/- 31 nmol/ml/min vs. 68 +/- 18 nmol/ml/min, p = 0.021) and oxidation (85 +/- 30 nmol/ml/min vs. 63 +/- 19 nmol/ml/min, p = 0.007) were increased. There were no differences in myocardial HEP metabolism or perfusion. No association was found between LV diastolic function and cardiac substrate or HEP metabolism.
Patients versus control subjects showed impaired LV diastolic function and altered myocardial substrate metabolism, but unchanged HEP metabolism. We found no direct relation between cardiac diastolic function and parameters of myocardial metabolism.