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<jats:p> <jats:bold>Rationale:</jats:bold> The recent development of hyperpolarized <jats:sup>13</jats:sup> C Magnetic Resonance Spectroscopy (MRS) has made it possible to measure cellular metabolism in vivo, in real time. </jats:p> <jats:p> <jats:bold>Objective:</jats:bold> 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. </jats:p> <jats:p> <jats:bold>Methods and Results:</jats:bold> 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 ( <jats:sup>31</jats:sup> P-MRS) and lipid content ( <jats:sup>1</jats:sup> H-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- <jats:sup>13</jats:sup> C]pyruvate via pyruvate dehydrogenase (PDH, [ <jats:sup>13</jats:sup> C]bicarbonate), lactate dehydrogenase ([1- <jats:sup>13</jats:sup> C]lactate) and alanine transaminase ([1- <jats:sup>13</jats:sup> C]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. </jats:p> <jats:p> <jats:bold>Conclusions:</jats:bold> This work represents the first demonstration of the ability of hyperpolarized <jats:sup>13</jats:sup> C 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. </jats:p>

Original publication

DOI

10.1161/circresaha.119.316260

Type

Journal article

Journal

Circulation Research

Publisher

Ovid Technologies (Wolters Kluwer Health)

Publication Date

05/02/2020