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Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

¹ Section of Nutrition/Metabolism, Department of Internal Medicine, Istituto Scientifico San Raffaele, Milano, Italy
² Unit of Clinical Spectroscopy, Istituto Scientifico San Raffaele, Milano, Italy
³ Faculty of Exercise Sciences, Center of "Physical Exercise for Health and Wellness"; Università degli Studi di Milano; Milan, Italy
⁴ Division of Diagnostic Radiology, Istituto Scientifico San Raffaele, Milano, Italy
⁵ Division of Nuclear Medicine, Istituto Scientifico San Raffaele, Milano, Italy
⁶ Università Vita e Salute San Raffaele, Milan Italy

Address correspondence and reprint requests to Gianluca Perseghin, MD, Faculty of Exercise Sciences, Università degli Studi di Milano and Internal Medicine/Unit of Clinical Spectroscopy Istituto Scientifico San Raffaele, via Olgettina 60, 20132, Milano Italy. Email: perseghin.gianluca{at}hsr.it

OBJECTIVE—Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques.

RESEARCH DESIGN AND METHODS—We studied 81 healthy men (aged 22–55 years, with BMI between 19 and 35 kg/m²) by means of cardiac magnetic resonance imaging and ³¹P-magnetic resonance spectroscopy in the resting and fasted conditions and stratified them in quartiles of BMI (cut offs: 23.2, 25.5 and 29.0 kg/m²).

RESULTS—LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean ± SD BMI (2.25 ± 0.52, 1.89 ± 0.26, 1.99 ± 0.38, and 1.79 ± 0.29; P < 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome.

CONCLUSIONS—Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia.

Abbreviations: FFA, free fatty acid • HOMA, homeostasis model assessment • HOMA-S%, HOMA of insulin sensitivity • LV, left ventricular • MRI, magnetic resonance imaging • MRS, ³¹P-magnetic resonance spectroscopy • PCr, phosphocreatine • TSH, thyroid-stimulating hormone

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