PMID- 32078413 OWN - NLM STAT- MEDLINE DCOM- 20201030 LR - 20240210 IS - 1524-4571 (Electronic) IS - 0009-7330 (Print) IS - 0009-7330 (Linking) VI - 126 IP - 6 DP - 2020 Mar 13 TI - Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized (13)C MRI. PG - 725-736 LID - 10.1161/CIRCRESAHA.119.316260 [doi] AB - RATIONALE: The recent development of hyperpolarized (13)C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time. OBJECTIVE: 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. METHODS AND RESULTS: 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 ((31)P-magnetic resonance spectroscopy), and lipid content ((1)H-magnetic resonance spectroscopy) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1-(13)C]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-(13)C]pyruvate via PDH (pyruvate dehydrogenase, [(13)C]bicarbonate), lactate dehydrogenase ([1-(13)C]lactate), and alanine transaminase ([1-(13)C]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. CONCLUSIONS: This work represents the first demonstration of the ability of hyperpolarized (13)C 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. FAU - Rider, Oliver J AU - Rider OJ AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Apps, Andrew AU - Apps A AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Miller, Jack J J J AU - Miller JJJJ AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. AD - Department of Physiology, Anatomy and Genetics (J.J.J.J.M., J.Y.C.L., D.J.T.), University of Oxford, United Kingdom. AD - Department of Physics (J.J.J.J.M.), University of Oxford, United Kingdom. FAU - Lau, Justin Y C AU - Lau JYC AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. AD - Department of Physiology, Anatomy and Genetics (J.J.J.J.M., J.Y.C.L., D.J.T.), University of Oxford, United Kingdom. FAU - Lewis, Andrew J M AU - Lewis AJM AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Peterzan, Mark A AU - Peterzan MA AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Dodd, Michael S AU - Dodd MS AD - School of Life Sciences, Coventry University, United Kingdom (M.S.D.). FAU - Lau, Angus Z AU - Lau AZ AD - Sunnybrook Research Institute, Toronto, Canada (A.Z.L.). FAU - Trumper, Claire AU - Trumper C AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Gallagher, Ferdia A AU - Gallagher FA AD - Department of Radiology (F.A.G., J.T.G.), University of Cambridge, United Kingdom. FAU - Grist, James T AU - Grist JT AD - Department of Radiology (F.A.G., J.T.G.), University of Cambridge, United Kingdom. FAU - Brindle, Kevin M AU - Brindle KM AD - Cancer Research UK Cambridge Institute (K.M.B.), University of Cambridge, United Kingdom. FAU - Neubauer, Stefan AU - Neubauer S AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. FAU - Tyler, Damian J AU - Tyler DJ AD - From the Oxford Centre for Clinical Magnetic Resonance Research, Radcliffe Department of Medicine (O.J.R., A.A., J.J.J.J.M., J.Y.C.L., A.J.M.L., M.A.P., C.T., S.N., D.J.T.), University of Oxford, United Kingdom. AD - Department of Physiology, Anatomy and Genetics (J.J.J.J.M., J.Y.C.L., D.J.T.), University of Oxford, United Kingdom. LA - eng GR - FS/15/80/31803/BHF_/British Heart Foundation/United Kingdom GR - RE/08/004/23915/BHF_/British Heart Foundation/United Kingdom GR - G0601490/MRC_/Medical Research Council/United Kingdom GR - RE/13/1/30181/BHF_/British Heart Foundation/United Kingdom GR - FS/14/54/30946/BHF_/British Heart Foundation/United Kingdom GR - RG/11/9/28921/BHF_/British Heart Foundation/United Kingdom GR - WT_/Wellcome Trust/United Kingdom GR - 16465/CRUK_/Cancer Research UK/United Kingdom GR - FS/17/18/32449/BHF_/British Heart Foundation/United Kingdom GR - FS/19/18/34252/BHF_/British Heart Foundation/United Kingdom GR - 27150/CRUK_/Cancer Research UK/United Kingdom GR - FS/14/17/30634/BHF_/British Heart Foundation/United Kingdom GR - 16628/CRUK_/Cancer Research UK/United Kingdom GR - 17242/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200205 PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Pyruvate Dehydrogenase Complex) RN - 8558G7RUTR (Pyruvic Acid) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 2.6.1.2 (Alanine Transaminase) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Aged MH - Aged, 80 and over MH - Alanine Transaminase/metabolism MH - Diabetes Mellitus, Type 2/*diagnostic imaging/metabolism MH - Fasting/metabolism MH - Female MH - Glucose/metabolism MH - Humans MH - L-Lactate Dehydrogenase/metabolism MH - Magnetic Resonance Imaging/*methods MH - Male MH - Middle Aged MH - Myocardium/*metabolism MH - Pyruvate Dehydrogenase Complex/metabolism MH - Pyruvic Acid/metabolism PMC - PMC7077975 OTO - NOTNLM OT - diabetes mellitus OT - diabetic cardiomyopathy OT - hyperpolarized magnetic resonance spectroscopy OT - magnetic resonance imaging OT - metabolism OT - pyruvate dehydrogenase EDAT- 2020/02/23 06:00 MHDA- 2020/10/31 06:00 PMCR- 2020/03/17 CRDT- 2020/02/21 06:00 PHST- 2020/02/23 06:00 [pubmed] PHST- 2020/10/31 06:00 [medline] PHST- 2020/02/21 06:00 [entrez] PHST- 2020/03/17 00:00 [pmc-release] AID - 10.1161/CIRCRESAHA.119.316260 [doi] PST - ppublish SO - Circ Res. 2020 Mar 13;126(6):725-736. doi: 10.1161/CIRCRESAHA.119.316260. Epub 2020 Feb 5.