Abnormal Cardiac and Skeletal Muscle Energy Metabolism in Patients With Type 2 Diabetes
Open accessAbstract
Background— It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism. Methods and Results— We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac high-energy phosphate metabolites were measured at rest using 31 P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31 P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50±0.11, than the healthy volunteers, at 2.30±0.12. The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free fatty acid concentrations. Although skeletal muscle energetics and pH were normal at rest, PCr loss and pH decrease were significantly faster during exercise in the patients with diabetes, who had lower exercise tolerance. After exercise, PCr recovery was slower in the patients with diabetes and correlated with tissue reoxygenation times. The exercise times correlated negatively with the deoxygenation rates and the hemoglobin (Hb)A 1c levels and the reoxygenation times correlated positively with the HbA 1c levels. Conclusions— Type 2 diabetic patients with apparently normal cardiac function have impaired myocardial and skeletal muscle energy metabolism related to changes in circulating metabolic substrates.
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Subjects with type 2 diabetes have decreased exercise tolerance and impaired recovery of intracellular phosphocreatinine concentration after exercise.
“Subjects with T2DM also have decreased exercise tolerance and impaired recovery of intracellular phosphocreatinine concentration following exercise [107, 108]”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [107]
31P-NMR studies show decreased phosphocreatine/ATP ratios in cardiac tissue of obese and type 2 diabetes subjects.
“31 P-NMR studies show decreased phosphocreatine/ATP ratios in cardiac tissue of obese and T2D subjects (112-114).”
From Altered mitochondrial function in insulin-deficient and insulin-resistant states (2018) · cites this paper as [114]
Cites
Cytosolic phosphorylation potential.
Veech, R. L., Lawson, J., Cornell, N. W., & Krebs, H. A. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50401-4 · Cited by 922 · see citing works
Neubauer, S., Horn, M., Cramer, M., Harre, K., Newell, J. B., Peters, W., Pabst, T., Ertl, G., Hahn, D., Ingwall, J. S., et al. (1997) · Circulation · doi:10.1161/01.cir.96.7.2190 · Cited by 748 · see citing works
Self-citationGlycemic Control and Heart Failure Among Adult Patients With Diabetes
Iribarren, C., Karter, A. J., Go, A. S., Ferrara, A. M., Liu, J. Y., Sidney, S. S., & Selby, J. V. (2001) · Circulation · doi:10.1161/01.cir.103.22.2668 · Cited by 703 · see citing works
Adaptation and Maladaptation of the Heart in Diabetes: Part I
Taegtmeyer, H., McNulty, P. H., & Young, M. E. (2002) · Circulation · doi:10.1161/01.cir.0000012466.50373.e8 · Cited by 517 · see citing works
Regulation of energy substrate metabolism in the diabetic heart
Stanley, W. (1997) · Cardiovascular Research · doi:10.1016/s0008-6363(97)00047-3 · Cited by 480 · see citing works
Near-infrared oximetry of the brain
Madsen, P. L., & Secher, N. H. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00093-8 · Cited by 316 · see citing works
Self-citationMetabolic disturbances in diabetic cardiomyopathy.
Rodrigues, B. B., Cam, M. C., & McNeill, J. H. (1998) · PubMed · Cited by 248 · see citing works
Baron, A., Laakso, M., Brechtel, G., & Edelman, S. V. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-3-637 · Cited by 210 · see citing works
Type 2 Diabetes Mellitus: Update on Diagnosis, Pathophysiology, and Treatment
Mahler, R. J., & Adler, M. L. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.4.5612 · Cited by 206 · see citing works
Metabolic disturbances in diabetic cardiomyopathy
Rodrigues, B. B., Cam, M. C., & McNeill, J. H. (1998) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006882805197 · Cited by 197 · see citing works
Sidell, R. J., Cole, M. A., Draper, N. J., Desrois, M., Buckingham, R. E., & Clarke, K. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1110 · Cited by 165 · see citing works
Self-citationIncreased uncoupling proteins and decreased efficiency in palmitate-perfused hyperthyroid rat heart
Boehm, E. A., Jones, B. E., Radda, G. K., Veech, R. L., & Clarke, K. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.3.h977 · Cited by 128 · see citing works
Self-citationDiabetic Macrovascular Disease
Libby, P., & Plutzky, J. (2002) · Circulation · doi:10.1161/01.cir.0000037282.92395.ae · Cited by 126 · see citing works
Cardiac carbohydrate metabolism in Zucker diabetic fatty rats
Chatham, J. C. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00399-1 · Cited by 118 · see citing works
The Association Between Diabetic Complications and Exercise Capacity in NIDDM Patients
Estacio, R. O., Regensteiner, J. G., Wolfel, E. E., Jeffers, B., Dickenson, M., & Schrier, R. W. (1998) · Diabetes Care · doi:10.2337/diacare.21.2.291 · Cited by 111 · see citing works
Cardiovascular mortality and morbidity in type-2 diabetes mellitus
Schernthaner, G.-H. (1996) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(96)01224-7 · Cited by 96 · see citing works
Komiyama, T., Shigematsu, H., Yasuhara, H., & Muto, T. (2000) · British journal of surgery · doi:10.1046/j.1365-2168.2000.01381.x · Cited by 79 · see citing works
Myocardial Blood Flow and Glucose Metabolism in Diabetes Mellitus
Meyer, C., & Schwaiger, M. (1997) · The American Journal of Cardiology · doi:10.1016/s0002-9149(97)00463-3 · Cited by 60 · see citing works
Lodi, R., Kemp, G. J., Francesco Muntoni, A., Thompson, C. H., Rae, C. D., Taylor, J., Styles, P., & Taylor, D. J. (1999) · Brain · doi:10.1093/brain/122.1.121 · Cited by 59 · see citing works
Self-citationChatham, J. C. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00056-5 · Cited by 56 · see citing works
Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy
Crilley, J. G., Boehm, E. A., Rajagopalan, B., et al. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00960-8 · Cited by 53 · see citing works
Iozzo, P., Chareonthaitawee, P., Rimoldi, O. E., Betteridge, D. J., Camici, P. G., & Ferrannini, E. (2002) · Diabetologia · doi:10.1007/s00125-002-0917-3 · Cited by 51 · see citing works
Serum HbA1c Levels and Exercise Capacity in Diabetic Patients
Demir, İ., Ermiş, C., Altunbaş, H., et al. (2001) · Japanese Heart Journal · doi:10.1536/jhj.42.607 · Cited by 31 · see citing works
Coronary blood flow control is impaired at rest and during exercise in conscious diabetic dogs
Tune, J. D., Yeh, C., Setty, S., et al. (2002) · Basic Research in Cardiology · doi:10.1007/s003950200018 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Abel, E. D., Litwin, S. E., & Sweeney, G. (2008) · Physiological Reviews · doi:10.1152/physrev.00017.2007 · Cited by 736 · see citing works
Pathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670 · see citing works
The role of mitochondria in insulin resistance and type 2 diabetes mellitus
Szendroedi, J., Phielix, E., & Roden, M. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.138 · Cited by 600 · see citing works
Mitochondrial uncoupling, ROS generation and cardioprotection
Cadenas, S. (2018) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2018.05.019 · Cited by 591 · see citing works
Boudina, S., Sena, S., O’Neill, B. T., Tathireddy, P., Young, M. E., & Abel, E. D. (2005) · Circulation · doi:10.1161/circulationaha.105.554360 · Cited by 502 · see citing works
Mazumder, P. K., O’Neill, B. T., Roberts, M. W., Buchanan, J., Yun, U. J., Cooksey, R. C., Boudina, S., & Abel, E. D. (2004) · Diabetes · doi:10.2337/diabetes.53.9.2366 · Cited by 437 · see citing works
Montaigne, D., Marechal, X., Coisne, A., Debry, N., Modine, T., Fayad, G., Potelle, C., El Arid, J.-M., Mouton, S., Sebti, Y., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.008476 · Cited by 322 · see citing works
Boudina, S., Bugger, H., Sena, S., O'Neill, B. T., Zaha, V. G., Ilkun, O., Wright, J. J., Mazumder, P. K., Palfreyman, E., Tidwell, T. J., et al. (2009) · Circulation · doi:10.1161/circulationaha.108.792101 · Cited by 301 · see citing works
Fatty acid metabolism is enhanced in type 2 diabetic hearts
Carley, A. N., & Severson, D. L. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.03.005 · Cited by 232 · see citing works
Altered mitochondrial function in insulin-deficient and insulin-resistant states
Ruegsegger, G. N., Creo, A. L., Cortes, T. M., Dasari, S., & Nair, K. S. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120843 · Cited by 202 · see citing works
Ectopic lipids and organ function.
Szendroedi, J., & Roden, M. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328321b3a8 · Cited by 200 · see citing works
Mitochondrial Uncoupling: A Key Contributor to Reduced Cardiac Efficiency in Diabetes
Boudina, S., & Abel, E. D. (2006) · Physiology · doi:10.1152/physiol.00008.2006 · Cited by 199 · see citing works
The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance
Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154 · see citing works
Mitochondrial dysfunction, insulin resistance, and type 2 diabetes mellitus
Abdul-Ghani, M. A., & DeFronzo, R. A. (2008) · Current Diabetes Reports · doi:10.1007/s11892-008-0030-1 · Cited by 146 · see citing works
Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study
Kioumourtzoglou, M.-A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., & Weisskopf, M. G. (2015) · JAMA Neurology · doi:10.1001/jamaneurol.2015.0910 · Cited by 145 · see citing works
De Feyter, H. M., van den Broek, N. M. A., Praet, S. F. E., Nicolay, K., van Loon, L. J. C., & Prompers, J. J. (2008) · European Journal of Endocrinology · doi:10.1530/eje-07-0756 · Cited by 116 · see citing works
van der Meer, R. W., Hammer, S., Lamb, H. J., Frölich, M., Diamant, M., Rijzewijk, L. J., de Roos, A., Romijn, J. A., & Smit, J. W. A. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-2524 · Cited by 113 · see citing works
Cardiopulmonary Impairment in Young Women with Polycystic Ovary Syndrome
Orio, F., Giallauria, F., Palomba, S., Cascella, T., Manguso, F., Vuolo, L., Russo, T., Tolino, A., Lombardi, G., Colao, A., et al. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0216 · Cited by 84 · see citing works
Wang, P., & Chatham, J. C. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00295.2003 · Cited by 81 · see citing works
Creatine for the Treatment of Depression
Kious, B. M., Kondo, D. G., & Renshaw, P. F. (2019) · Biomolecules · doi:10.3390/biom9090406 · Cited by 74 · see citing works
Stewart, K. J. (2004) · Cardiology Clinics · doi:10.1016/j.ccl.2004.06.007 · Cited by 72 · see citing works
Mitochondrial involvement in skeletal muscle insulin resistance: A case of imbalanced bioenergetics
Affourtit, C. (2016) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.07.008 · Cited by 67 · see citing works
Perseghin, G., Ntali, G., De Cobelli, F., Lattuada, G., Esposito, A., Belloni, E., Canu, T., Costantino, F., Ragogna, F., Scifo, P., et al. (2007) · Diabetes Care · doi:10.2337/dc06-2429 · Cited by 65 · see citing works
Wu, J. S., Buettner, C., Smithline, H., Ngo, L. H., & Greenman, R. L. (2011) · Muscle & Nerve · doi:10.1002/mus.21847 · Cited by 61 · see citing works
Mitochondrial function and diabetes: consequences for skeletal and cardiac muscle metabolism
Schrauwen-Hinderling, V. B., Kooi, M. E., & Schrauwen, P. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2015.6291 · Cited by 47 · see citing works
- Authors
- Scheuermann-Freestone, M., Madsen, P. L., Manners, D., Blamire, A. M., Buckingham, R. E., Styles, P., Radda, G. K., Neubauer, S., & Clarke, K.
- Affiliations
- From the Departments of Biochemistry (M.S.-F., P.L.M., D.M., A.M.B., P.S., G.K.R., K.C.) and Cardiovascular Medicine (M.S.-F., S.N.), University of Oxford; MRC Biochemical and Clinical Magnetic Resonance Unit (M.S.-F., D.M., A.M.B., P.S.), John Radcliffe Hospital, Oxford; and GlaxoSmithKline (R.E.B.), Harlow, Essex, England.
- GlaxoSmithKline (United Kingdom) (GB)
- Venue
- Circulation
- Published
- 2003-06-24
- Volume
- 107
- Issue
- 24
- Pages
- 3040-3046
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2106755489
- Cited by
- 525
- References
- 24
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 17 · 2023: 18 · 2022: 19 · 2021: 34 · 2020: 26 · 2019: 26 · 2018: 29 · 2017: 24 · 2016: 30 · 2015: 29 · 2014: 30 · 2013: 16 · 2012: 26
- FWCI
- 10.34
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- British Heart Foundation (PS/02/002/14893)
- Fondation pour la Recherche Médicale
- Medical Research Council
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- type 2 diabetes, myocardial energy metabolism, skeletal muscle energy metabolism, high-energy phosphate metabolism, phosphocreatine, PCr/ATP ratio, free fatty acids, exercise tolerance, intracellular pH, HbA1c, cardiovascular risk
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Blood Glucose, Diabetes Mellitus, Type 2, Energy Metabolism, Fatty Acids, Nonesterified, Female, Glycated Hemoglobin, Humans, Hydrogen-Ion Concentration, Intracellular Fluid, Lipids, Male, Middle Aged, Myocardium, Magnetic Resonance Spectroscopy, Oxygen, Phosphocreatine, Phosphorus Isotopes, Reference Values, Muscle, Skeletal, Spectroscopy, Near-Infrared
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