84 Participants with T2DM have improved cardiac function with fatty acid metabolism, despite unchanged cardiac energetics

Background/IntroductionThe Phosphocreatine-to-Adenosine Triphosphate ratio (PCr/ATP) is an established indicator of cardiac energetic status. Measurement of the Creatine Kinase pseudo-first order rate constant (CKkf) provides a more sensitive measure of cardiac energetics, and allows calculation of ATP delivery rate through the Creatine Kinase shuttle (CK flux). The normal heart is metabolically flexible and so should maintain energetics and cardiac output regardless of substrate available for use (fatty acids, FA, or glucose). This flexibility may be impaired in type 2 diabetes mellitus (T2DM), contributing to diabetic cardiomyopathy. However, it is unknown to what extent flexibility can be influenced by artificially altering the substrate available for metabolism.PurposeTo compare cardiac function and energetics in diabetic participants randomised to either Intralipid© or a glycaemic clamp, to increase FA and glucose supply respectively.MethodsAt 2 separate visits (> 7 days apart), fasted participants with T2DM and normal cardiac systolic function received intravenous infusions of either 20% intralipid© (Intra, 60ml/hr) or insulin/dextrose 20% (Ins/Dex, variable rate), before undergoing multi-parametric cardiac MRI at 3 Tesla with standard imaging for LV volumes and left ventricular ejection fraction (LVEF), and 31P MR spectroscopy for PCR/ATP ratio and CKkf (s-1). ATP delivery rate was calculated as CKkf .[PCR]. [ATP] was assumed to be 5.7μmol (g wet weight)-1, and [PCr] calculated as PCr/ATP x 5.7.ResultsTwelve participants (11 male, age 60.3 ± 7.4 years, BMI 27.9 ± 5.3 kg/m2) were recruited. LVEF was increased on Intra vs Ins/Dex (biplane calculation: 69.1 ± 6.4 % vs 63.3 ± 5.7 %, p=0.007; short axis stack calculation 64.3 ± 4.0 % vs 62.2 ± 4.9 %, p=0.065). In addition, peak circumferential strain was increased on Intra (-20.69 ± 2.26 % vs -18.96 ± 1.72 %, p=0.002). Despite this, altering substrate did not influence PCR/ATP (Intra 1.84 ± 0.37; Ins/Dex 1.80 ± 0.29, p = 0.99), CKkf (Intra 0.15 ± 0.07 s-1; Ins/Dex 0.18 ± 0.09 s-1, p= 0.28) or CK flux (Intra 1.60 ± 0.79 μmol (g wet weight)−1 s-1; Ins/Dex 1.85 ± 0.90 μmol (g wet weight)−1 s-1, p=0.32).ConclusionParticipants with T2DM have increased systolic function when using fatty acid as opposed to glucose as their predominant metabolic substrate. However, there is no change in cardiac energetics, implying either improved metabolic efficiency or increased ATP delivery via a CK independent route.Conflict