Myocardial glucose transport and utilization in patients with type 2 diabetes mellitus, left ventricular dysfunction, and coronary artery disease.
OBJECTIVE
This research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease.


BACKGROUND
Patients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose.


METHODS
Myocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by 18F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts.


RESULTS
Myocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 +/- 0.16 vs. 0.47 +/- 0.24 micromol x min(-1) x g(-1), p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 +/- 3.1% vs. 13.5 +/- 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75).


CONCLUSIONS
Patients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients.
Dutka
David P
DP
Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, United Kingdom. dpd24@cam.ac.uk
Pitt
Michael
M
Pagano
Domenico
D
Mongillo
Marco
M
Gathercole
David
D
Bonser
Robert S
RS
Camici
Paolo G
PG
D000368:Aged; D015153:Blotting, Western; D002303:Cardiac Output, Low / Q000209:etiology / Q000378:metabolism; D003324:Coronary Artery Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000378:metabolism
D051275:Glucose Transporter Type 4; D019275:Radiopharmaceuticals; C495692:SLC2A4 protein, human; D019788:Fluorodeoxyglucose F18; D005947:Glucose