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CLINICAL RESEARCH: CORONARY ARTERY DISEASE AND CARDIAC METABOLISM

Myocardial Glucose Transport and Utilization in Patients With Type 2 Diabetes Mellitus, Left Ventricular Dysfunction, and Coronary Artery Disease

David P. Dutka, MD, FRCP^_*,_*, Michael Pitt, FRCP, Domenico Pagano, MD, FRCS, Marco Mongillo, MD, PhD, David Gathercole, BSc, PhD, Robert S. Bonser, FRCS, FRCP and Paolo G. Camici, MD, FESC, FACC, FAHA, FRCP

^_* Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kingdom
MRC Clinical Sciences Centre & National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.

Manuscript received January 12, 2006; revised manuscript received April 11, 2006, accepted June 8, 2006.

^_* Reprint requests and correspondence: Dr. David P. Dutka, Department of Cardiovascular Medicine, ACCI, Level 6, Box 110, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, United Kingdom. (Email: dpd24{at}cam.ac.uk).

OBJECTIVES: This research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease.

BACKGROUND: Patients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose.

METHODS: Myocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by ¹⁸F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts.

RESULTS: Myocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 ± 0.16 vs. 0.47 ± 0.24 µmol·min^–1·g^–1, p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 ± 3.1% vs. 13.5 ± 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75).

CONCLUSIONS: Patients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients.

Abbreviations and Acronyms   CABG = coronary artery bypass grafting   CAD = coronary artery disease   FDG = 18F-flurodeoxyglucose   FFA = free fatty acid   GLUT4 = glucose transporter 4   LV = left ventricle/ventricular   MBF = myocardial blood flow   MGU = myocardial glucose utilization   PET = positron emission tomography   PPAR = peroxisome proliferator-activated receptor   PTF = perfusable tissue fraction   ROI = region of interest   TACs = time-activity curves   T2DM = type 2 diabetes mellitus

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