Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes.
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.


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 31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31P 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)A1c levels and the reoxygenation times correlated positively with the HbA1c 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.
Scheuermann-Freestone
Michaela
M
Department of Biochemistry, University of Oxford, Oxford OX1 3PT, England.
Madsen
Per L
PL
Manners
David
D
Blamire
Andrew M
AM
Buckingham
Robin E
RE
Styles
Peter
P
Radda
George K
GK
Neubauer
Stefan
S
Clarke
Kieran
K
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000378:metabolism*; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000378:metabolism; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000032:analysis; D012016:Reference Values; D019265:Spectroscopy, Near-Infrared
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006442:Glycated Hemoglobin; D008055:Lipids; D010100:Oxygen; D010725:Phosphocreatine; D010759:Phosphorus Isotopes