Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance

Background. Because studies in animal models of type-2 diabetes mellitus (DM) show that excessive myocardial fatty acid (FA) metabolism (at the expense of glucose metabolism) cause cardiac dysfunction, we hypothesized that women with DM would have more FA and less glucose myocardial metabolism than normal or even obese (OB) women. Research Design and Methods. Women who were lean volunteers (NV) (N 5 14; age 35 ± 17 years, body mass index 23 ± 1 kg/m²), OB (N 5 28;31 ± 6 years, BMI 39 ± 7 kg/m ²), and DM (n 5 22; 54 ± 11 years, BMI 38 ± 5 kg/m ²) were studied. Cardiac positron emission tomography was performed for the determination of myocardial blood flow, oxygen consumption, FA and glucose metabolism. Cardiac work was measured by echocardiography and efficiency by the ratio of work to myocardial oxygen consumption. Results. Fractional glucose uptake was comparable between NV and OB but lower in DM (P < .05 versus NV). Myocardial FA utilization and oxidation were both higher in DM compared with NV and OB (P < .0001). Myocardial FA utilization and oxidation had positive correlations with HOMA (R 5 0.35, P 5 .005 and R 5 0.40, P 5 .001, respectively) whereas fractional glucose uptake exhibited an inverse correlation (R 5 2.31, P 5 .01). Cardiac work and efficiency were similar among the three groups. Conclusions. In women, the presence of OB and DM compared with OB alone is associated with a greater reliance on myocardial FA metabolism at the expense of glucose metabolism. These perturbations in myocardial metabolism are not associated in a decline left ventricular efficiency or function suggesting that the metabolic perturbations may precede an eventual decline left ventricular function as is seen in animal models of DM.