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Diabetes 54:2787-2794, 2005
© 2005 by the American Diabetes Association, Inc.

Rosiglitazone Improves Myocardial Glucose Uptake in Patients With Type 2 Diabetes and Coronary Artery Disease

A 16-Week Randomized, Double-Blind, Placebo-Controlled Study

Riikka Lautamäki1, K.E. Juhani Airaksinen2, Marko Seppänen1,3, Jyri Toikka3, Matti Luotolahti3, Elizabeth Ball4, Ronald Borra1, Risto Härkönen3, Patricia Iozzo1,5, Murray Stewart4, Juhani Knuuti1, and Pirjo Nuutila1,2

1 Turku PET Centre, University of Turku, Turku, Finland
2 Department of Medicine, University of Turku, Turku, Finland
3 Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku, Finland
4 GlaxoSmithKline, Greenford, U.K
5 Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy

Rosiglitazone therapy improves insulin sensitivity and glucose uptake in patients with uncomplicated type 2 diabetes. In coronary artery disease (CAD), glucose is an important source of energy and preserved myocardial glucose uptake is essential for the viability of jeopardized myocardium. The aim was to test whether rosiglitazone changes myocardial metabolism in type 2 diabetic patients with CAD. We studied 54 patients (38 men and 16 women) with type 2 diabetes (HbA1c 7.2 + 0.9%) and CAD. Myocardial glucose uptake was measured with [18F]fluoro-2-deoxy-D-glucose positron emission tomography in ischemic (evaluated by single-photon emission tomography and coronary angiography) and nonischemic regions during euglycemic-hyperinsulinemic clamp before and after a 16-week intervention period with rosiglitazone (n = 27) or placebo (n = 27). Rosiglitazone significantly improved glycemic control (P < 0.0001) and whole-body insulin sensitivity (P < 0.0001). Rosiglitazone increased myocardial glucose uptake from 20.6 ± 11.8 to 25.5 ± 12.4 µmol · 100 g–1 · min–1 (P = 0.038 vs. baseline, P = 0.023 vs. placebo) in ischemic regions and from 21.7 ± 12.1 to 28.0 ± 12.7 µmol · 100 g–1 · min–1 (P = 0.014 vs. baseline, P = 0.003 vs. placebo) in nonischemic regions. The increase in myocardial glucose uptake was partly explained by the suppression of free fatty acid levels during clamp. Rosiglitazone therapy significantly increased insulin sensitivity and improved myocardial glucose uptake in type 2 diabetic patients with CAD. These results suggest that rosiglitazone therapy may facilitate myocardial glucose storage and utilization in these patients.

Address correspondence and reprint requests to Dr. Riikka Lautamäki, Turku PET Centre, Turku University Central Hospital, Kiinamyllynkatu 4-8, P.O. Box 52, FIN-20521 Turku, Finland. E-mail: rimala{at}utu.fi

Abbreviations: CAD, coronary artery disease; FDG, fluoro-2-deoxy-D-glucose; FFA, free fatty acid; PET, positron emission tomography; PPAR{gamma}, peroxisome proliferator–activated receptor-{gamma}; SPECT, single-photon emission tomography


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