Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance
- 128 Downloads
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 = 14; age 35 ± 17 years, body mass index 23 ± 1 kg/m2), OB (N = 28;31 ± 6 years, BMI 39 ± 7 kg/m2), and DM (n = 22; 54 ± 11 years, BMI 38 ± 5 kg/m2) 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.
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 = 0.35, P = .005 and R = 0.40, P = .001, respectively) whereas fractional glucose uptake exhibited an inverse correlation (R = −.31, P = .01). Cardiac work and efficiency were similar among the three groups.
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.
KeywordsFatty acid imaging glucose metabolism: PET diabetes
Conflict of interest
The authors have indicated that they have no financial conflicts of interest.
- 16.Company MLI. Metropolitan height and weight tables. Stat Bull Metrop Life Found 1983;64:3-9.Google Scholar
- 21.Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: A report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-63.PubMedCrossRefGoogle Scholar
- 29.Turpeinen AK, Takala TO, Nuutila P, Axelin T, Luotolahti M, Haaparanta M, et al. Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: Studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Diabetes 1999;48:1245-50.PubMedCrossRefGoogle Scholar
- 30.Rijzewijk LJ, van der Meer RW, Lamb HJ, de Jong HW, Lubberink M, Romijn JA, et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: Studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 2009;54:1524-32.PubMedCrossRefGoogle Scholar
- 36.Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, et al. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: A 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 1999;48:1600-6.PubMedCrossRefGoogle Scholar