Insulin resistance in patients with cardiac hypertrophy.
OBJECTIVE
Animal studies suggest that left ventricular hypertrophy might be associated with insulin resistance and alterations in glucose transporters. We have previously demonstrated myocardial insulin resistance in patients with post-ischemic heart failure. The aim was to investigate whether myocardial insulin resistance could be demonstrated in human cardiac hypertrophy in the absence of hypertension, diabetes and coronary artery disease.


METHODS
Eleven normotensive nondiabetic patients with cardiac hypertrophy due to aortic stenosis and angiographically normal coronary arteries were compared to 11 normal volunteers. Myocardial glucose uptake (MGU) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose during fasting (low insulinemia) or during euglycemic-hyperinsulinemic clamp (physiologic hyperinsulinemia). Myocardial biopsies were obtained in order to investigate changes in insulin-independent (GLUT-1) and insulin-dependent (GLUT-4) glucose transporters.


RESULTS
During fasting, plasma insulin (7 +/- 1 vs. 6 +/- 1 mU/l) and MGU (0.12 +/- 0.05 vs. 0.11 +/- 0.04 mumol/min/g) were comparable in patients and controls. By contrast, during clamp, MGU was markedly reduced in patients (0.48 +/- 0.02 vs. 0.70 +/- 0.03 mumol/min/g, p < 0.01) despite similar plasma insulin levels (95 +/- 6 vs. 79 +/- 6 mU/l). A decreased GLUT-4/GLUT-1 ratio was shown by Western blot analysis in patients.


CONCLUSIONS
Insulin resistance seems to be a feature of the hypertrophied heart even in the absence of hypertension, coronary artery disease and diabetes and may be explained, at least in part, by abnormalities in glucose transporters.
Paternostro
G
G
MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Pagano
D
D
Gnecchi-Ruscone
T
T
Bonser
R S
RS
Camici
P G
PG
D001024:Aortic Valve Stenosis / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism; D015153:Blotting, Western; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism; D016022:Case-Control Studies; D005215:Fasting / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D012044:Regression Analysis; D018709:Statistics, Nonparametric; D014055:Tomography, Emission-Computed
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495677:SLC2A1 protein, human; C495692:SLC2A4 protein, human; D019788:Fluorodeoxyglucose F18; D005947:Glucose