Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus

R.W. van der Meer, L. Rijzewijk, H.W.A.M. de Jong, H.J. Lamb, J.M. Lubberink, J.A. Romijn, J.J. Bax, A.M. de Roos, O. Kamp, W.J. Paulus, R.J. Heine, A.A. Lammertsma, J.W.A. Smit, M. Diamant

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BACKGROUND: Cardiac disease is the leading cause of mortality in type 2 diabetes mellitus (T2DM). Pioglitazone has been associated with improved cardiac outcome but also with an elevated risk of heart failure. We determined the effects of pioglitazone on myocardial function in relation to cardiac high-energy phosphate, glucose, and fatty acid metabolism and triglyceride content in T2DM patients. METHODS AND RESULTS: Seventy-eight T2DM men without structural heart disease or inducible ischemia as assessed by dobutamine stress echocardiography were assigned to pioglitazone (30 mg/d) or metformin (2000 mg/d) and matching placebo for 24 weeks. The primary end point was change in cardiac diastolic function from baseline relative to myocardial metabolic changes, measured by magnetic resonance imaging, proton and phosphorus magnetic resonance spectroscopy, and [(18)F]-2-fluoro-2-deoxy-D-glucose and [(11)C]palmitate positron emission tomography. No patient developed heart failure. Both therapies similarly improved glycemic control, whole-body insulin sensitivity, and blood pressure. Pioglitazone versus metformin improved the early peak flow rate (P=0.047) and left ventricular compliance. Pioglitazone versus metformin increased myocardial glucose uptake (P
Original languageEnglish
Pages (from-to)2069-2077
Number of pages12
Issue number15
Publication statusPublished - 2009

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