Cardiac rest and stress metabolism in patients with type 2 diabetes (360G-Wellcome-207726_Z_17_Z)

Patients with T2D are at significant risk of developing heart failure and related complications. Altered myocardial fuel selection may play a central role in cardiac disease risk in patients with T2D, by affecting myocardial oxygen demand and metabolic flexibility. At any given level of cardiac work, an increased dependence on fatty acids (FA) relative to carbohydrates decreases cardiac efficiency, which may adversely affect cardiac function. Overall Aim: To evaluate, in vivo, the effect of T2D on myocardial energy metabolism and metabolic flexibility. Hypothesis: In patients with T2D i) myocardium is metabolically inflexible with a fixed FA preference and inability to increase glucose utilisation even in response to acute increases in cardiac workload; ii) the fixed preference of FA utilisation significantly contributes to abnormalities in contractile function. Methods: Cross sectional, case-control study. Population: 22 T2D patients and 22 non-diabetic individuals with preserved cardiac function. Investigations: Significant coronary artery disease will be excluded in all patients by coronary angiography. Myocardial metabolism will be determined at baseline and during dobutamine stress with measurement of transmyocardial arteriovenous differences of oxygen and metabolites. Participants will undergo a comprehensive evaluation of cardiac structure, function and perfusion using rest and dobutamine stress CMR.