Abstract
The recent development of hyperpolarized 13C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time. By comparing participants with and without type 2 diabetes mellitus (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. Thirteen people with T2DM (glycated hemoglobin, 6.9±1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics (31P-magnetic resonance spectroscopy), and lipid content (1H-magnetic resonance spectroscopy) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-13C]pyruvate magnetic resonance spectra were also acquired and in 5 of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75 g oral glucose challenge. Downstream metabolism of [1-13C]pyruvate via PDH (pyruvate dehydrogenase, [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 T2DM (Fasted: 0.0084±0.0067 [Control] versus 0.0016±0.0014 [T2DM], Fed: 0.0184±0.0109 versus 0.0053±0.0041; P=0.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (P<0.001). As is characteristic of diabetes mellitus, impaired myocardial energetics, myocardial lipid content, and diastolic function were also demonstrated in the wider study cohort. This work represents the first demonstration of the ability of hyperpolarized 13C magnetic resonance spectroscopy to noninvasively 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.
Highlights
This work represents the first demonstration of the ability of hyperpolarized 13C magnetic resonance spectroscopy to noninvasively assess physiological and pathological changes in cardiac metabolism in the human heart
We show here that hyperpolarized 13C magnetic resonance imaging (MRI) can detect increases in the metabolism of carbohydrates when people go from being fasted to fed and that carbohydrate metabolism is significantly reduced in the diabetic heart
Participants with type 2 diabetes mellitus (T2DM) had significantly higher body mass index than controls (22.6±3.0 versus 29.7±6.8; P=0.003), but baseline myocardial structural characteristics assessed by cine-magnetic resonance imaging including left ventricular ejection fraction (60±4% versus 57±6%; P=0.228), indexed left ventricular end-diastolic volume (82±12 versus 79±15 mL/m2; P=0.577) and myocardial mass index (64±10 versus 62±11 g/m2; P=0.658), were not different between groups (Table 1)
Summary
The data that support the findings of this study are available from the corresponding author on reasonable request.Study Cohort and Study VisitThis research was approved by the National Research Ethics Committee service (13/SW/0108) and conducted in accordance with the declaration of Helsinki and the Caldicott principles. The data that support the findings of this study are available from the corresponding author on reasonable request. This research was approved by the National Research Ethics Committee service (13/SW/0108) and conducted in accordance with the declaration of Helsinki and the Caldicott principles. All data collection was undertaken at the Oxford Subjects with T2DM who were taking the oral antihyperglycemic drug, Metformin, were asked to refrain from taking their medication for 12 hours before the study to minimize any potential effect on cardiac redox state.[24]
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