Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus

Eylem Levelt, Christopher T. Rodgers, William T. Clarke, Masliza Mahmod, Rina Ariga, Jane M. Francis, Alexander Liu, Rohan S. Wijesurendra, Saira Dass, Nikant Sabharwal, Matthew D. Robson, Cameron J. Holloway, Oliver J. Rider, Kieran Clarke, Theodoros D. Karamitsos, Stefan Neubauer

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Aims 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. Methods and results 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 (SID)]. 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 SID 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 SID (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SID. Conclusion 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.

Original languageEnglish
Pages (from-to)3461-3469
Number of pages9
JournalEuropean Heart Journal
Volume37
Issue number46
DOIs
Publication statusPublished - 1 Dec 2016
Externally publishedYes

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Workload
Type 2 Diabetes Mellitus
Perfusion
Phosphocreatine
Sudden Infant Death
Exercise
Adenosine Triphosphate
Oxygen
Coronary Artery Disease
Magnetic Resonance Spectroscopy
Diabetic Cardiomyopathies
Coronary Stenosis
Hypoglycemic Agents
Adenosine
Phosphorus
Leg
Angiography

Keywords

  • Coronary microvascular function
  • Diabetes mellitus
  • Diabetic cardiomyopathy
  • Metabolism
  • Oxygen

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Levelt, E., Rodgers, C. T., Clarke, W. T., Mahmod, M., Ariga, R., Francis, J. M., ... Neubauer, S. (2016). Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus. European Heart Journal, 37(46), 3461-3469. https://doi.org/10.1093/eurheartj/ehv442

Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus. / Levelt, Eylem; Rodgers, Christopher T.; Clarke, William T.; Mahmod, Masliza; Ariga, Rina; Francis, Jane M.; Liu, Alexander; Wijesurendra, Rohan S.; Dass, Saira; Sabharwal, Nikant; Robson, Matthew D.; Holloway, Cameron J.; Rider, Oliver J.; Clarke, Kieran; Karamitsos, Theodoros D.; Neubauer, Stefan.

In: European Heart Journal, Vol. 37, No. 46, 01.12.2016, p. 3461-3469.

Research output: Contribution to journalArticle

Levelt, E, Rodgers, CT, Clarke, WT, Mahmod, M, Ariga, R, Francis, JM, Liu, A, Wijesurendra, RS, Dass, S, Sabharwal, N, Robson, MD, Holloway, CJ, Rider, OJ, Clarke, K, Karamitsos, TD & Neubauer, S 2016, 'Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus', European Heart Journal, vol. 37, no. 46, pp. 3461-3469. https://doi.org/10.1093/eurheartj/ehv442
Levelt, Eylem ; Rodgers, Christopher T. ; Clarke, William T. ; Mahmod, Masliza ; Ariga, Rina ; Francis, Jane M. ; Liu, Alexander ; Wijesurendra, Rohan S. ; Dass, Saira ; Sabharwal, Nikant ; Robson, Matthew D. ; Holloway, Cameron J. ; Rider, Oliver J. ; Clarke, Kieran ; Karamitsos, Theodoros D. ; Neubauer, Stefan. / Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus. In: European Heart Journal. 2016 ; Vol. 37, No. 46. pp. 3461-3469.
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abstract = "Aims 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. Methods and results 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 (SID)]. 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 SID 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 SID (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SID. Conclusion 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.",
keywords = "Coronary microvascular function, Diabetes mellitus, Diabetic cardiomyopathy, Metabolism, Oxygen",
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T1 - Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus

AU - Levelt, Eylem

AU - Rodgers, Christopher T.

AU - Clarke, William T.

AU - Mahmod, Masliza

AU - Ariga, Rina

AU - Francis, Jane M.

AU - Liu, Alexander

AU - Wijesurendra, Rohan S.

AU - Dass, Saira

AU - Sabharwal, Nikant

AU - Robson, Matthew D.

AU - Holloway, Cameron J.

AU - Rider, Oliver J.

AU - Clarke, Kieran

AU - Karamitsos, Theodoros D.

AU - Neubauer, Stefan

PY - 2016/12/1

Y1 - 2016/12/1

N2 - Aims 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. Methods and results 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 (SID)]. 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 SID 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 SID (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SID. Conclusion 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.

AB - Aims 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. Methods and results 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 (SID)]. 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 SID 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 SID (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SID. Conclusion 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.

KW - Coronary microvascular function

KW - Diabetes mellitus

KW - Diabetic cardiomyopathy

KW - Metabolism

KW - Oxygen

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