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Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI.

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Rider, Oliver J 
Apps, Andrew 
Miller, Jack J 
Lau, Justin Yc 
Lewis, Andrew Jm 


Rationale: The recent development of hyperpolarized 13C Magnetic Resonance Spectroscopy (MRS) has made it possible to measure cellular metabolism in vivo, in real time. Objective: By comparing participants with and without type 2 diabetes (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart. Methods and Results: Thirteen people with type 2 diabetes (HbA1c 6.9{plus minus}1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics (31P-MRS) and lipid content (1H-MRS) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-13C]pyruvate MR spectra were also acquired and in five of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75g oral glucose challenge. Downstream metabolism of [1-13C]pyruvate via pyruvate dehydrogenase (PDH, [13C]bicarbonate), lactate dehydrogenase ([1-13C]lactate) and alanine transaminase ([1-13C]alanine) was assessed. Metabolic flux through cardiac PDH was significantly reduced in the people with type 2 diabetes (Fasted:0.0084{plus minus}0.0067[Control] vs. 0.0016{plus minus}0.0014[T2DM], Fed:0.0184{plus minus}0.0109 vs. 0.0053{plus minus}0.0041, p=.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (p<.001). As is characteristic of diabetes, impaired myocardial energetics, myocardial lipid content and diastolic function were also demonstrated in the wider study cohort. Conclusions: This work represents the first demonstration of the ability of hyperpolarized 13C MRS to non-invasively assess physiological and pathological changes in cardiac metabolism in the human heart. In doing so, we highlight the potential of the technique to detect and quantify metabolic alterations in the setting of cardiovascular disease.



diabetes mellitus, diabetic cardiomyopathy, hyperpolarized magnetic resonance spectroscopy, magnetic resonance imaging, metabolism, pyruvate dehydrogenase, Aged, Aged, 80 and over, Alanine Transaminase, Diabetes Mellitus, Type 2, Fasting, Female, Glucose, Humans, L-Lactate Dehydrogenase, Magnetic Resonance Imaging, Male, Middle Aged, Myocardium, Pyruvate Dehydrogenase Complex, Pyruvic Acid

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Circulation Research

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Wolters Kluwer Health


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Cancer Research UK (unknown)
Wellcome Trust (095962/Z/11/Z)
This study was funded by a programme grant from the British Heart Foundation (RG/11/9/28921). The authors would also like to acknowledge financial support provided by the British Heart Foundation (BHF) in the form of Clinical Research Training Fellowships, a BHF Intermediate Clinical Research Fellowship and a BHF Senior Research Fellowship respectively (OR: FS/14/54/30946, AA: FS/17/18/32449, AL: RE/08/004/23915, MP: FS/15/80/31803, DJT: FS/14/17/30634). JJM and MSD would like to acknowledge the financial support provided by Novo Nordisk Postdoctoral Fellowships. JJM would also like to acknowledge financial support from EPSRC. FAG would like to acknowledge Cancer Research UK (CRUK), the CRUK Cambridge Centre, the Wellcome Trust and the Cambridge Biomedical Research Centre. All authors would also like to acknowledge the support provided by the OXFORD-BHF Centre for Research Excellence (grant RE/13/1/30181) and the National Institute for Health Research Oxford Biomedical Research Centre programme.