title: Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus.
abstract: Patients with type 2 diabetes mellitus (T2DM) are known to have impaired resting myocardial energetics and impaired myocardial perfusion reserve, even in the absence of obstructive epicardial coronary artery disease (CAD). Whether or not the pre-existing energetic deficit is exacerbated by exercise, and whether the impaired myocardial perfusion causes deoxygenation and further energetic derangement during exercise stress, is uncertain.
  
  
  
  Thirty-one T2DM patients, on oral antidiabetic therapies with a mean HBA1c of 7.4 ± 1.3%, and 17 matched controls underwent adenosine stress cardiovascular magnetic resonance for assessment of perfusion [myocardial perfusion reserve index (MPRI)] and oxygenation [blood-oxygen level-dependent (BOLD) signal intensity change (SIΔ)]. Cardiac phosphorus-MR spectroscopy was performed at rest and during leg exercise. Significant CAD (>50% coronary stenosis) was excluded in all patients by coronary computed tomographic angiography. Resting phosphocreatine to ATP (PCr/ATP) was reduced by 17% in patients (1.74 ± 0.26, P = 0.001), compared with controls (2.07 ± 0.35); during exercise, there was a further 12% reduction in PCr/ATP (P = 0.005) in T2DM patients, but no change in controls. Myocardial perfusion and oxygenation were decreased in T2DM (MPRI 1.61 ± 0.43 vs. 2.11 ± 0.68 in controls, P = 0.002; BOLD SIΔ 7.3 ± 7.8 vs. 17.1 ± 7.2% in controls, P < 0.001). Exercise PCr/ATP correlated with MPRI (r = 0.50, P = 0.001) and BOLD SIΔ (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SIΔ.
  
  
  
  The pre-existing energetic deficit in diabetic cardiomyopathy is exacerbated by exercise; stress PCr/ATP correlates with impaired perfusion and oxygenation. Our findings suggest that, in diabetes, coronary microvascular dysfunction exacerbates derangement of cardiac energetics under conditions of increased workload.
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.|Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
authors.forename: Eylem
authors.initials: E
authors.lastname: Levelt
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Rodgers
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: William T
authors.initials: WT
authors.lastname: Clarke
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Masliza
authors.initials: M
authors.lastname: Mahmod
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Rina
authors.initials: R
authors.lastname: Ariga
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Jane M
authors.initials: JM
authors.lastname: Francis
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Rohan S
authors.initials: RS
authors.lastname: Wijesurendra
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Saira
authors.initials: S
authors.lastname: Dass
authors.affiliation: Oxford Heart Centre, John Radcliffe Hospital, Oxford, UK.
authors.forename: Nikant
authors.initials: N
authors.lastname: Sabharwal
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Robson
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.|Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.|St. Vincent's Hospital, Sydney, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Holloway
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Rider
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.|1st Department of Cardiology, AHEPA Hospital, Aristotle University, Thessaloniki, Greece.
authors.forename: Theodoros D
authors.initials: TD
authors.lastname: Karamitsos
authors.affiliation: Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK stefan.neubauer@cardiov.ox.ac.uk.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
mesh_terms: D003326:Coronary Circulation; D003924:Diabetes Mellitus, Type 2; D006801:Humans; D009206:Myocardium; D010725:Phosphocreatine; D016526:Workload
chemical_list: D010725:Phosphocreatine
keywords: Coronary microvascular function; Diabetes mellitus; Diabetic cardiomyopathy; Metabolism; Oxygen