Mechanism and significance of insulin resistance in myotonic dystrophy.
In order to elucidate the mechanism of the glucose intolerance frequently associated with myotonic dystrophy (MD), glucose metabolism of 10 patients and 10 controls was investigated using the following tests: successive intravenous stimulation of insulin secretion by glucose and tolbutamide, detection of serum islet cell antibodies, measure of the specific insulin binding on erythrocytes and evaluation in vivo of insulin sensitivity by the euglycaemic glucose clamp method. Glucose tolerance was decreased in MD patients (K value: 1.51 +/- 0.15 vs 2.4 +/- 0.2 X 10(-2)) in spite of a basal (26 +/- 4 vs 11 +/- 2 microU/ml) and post-stimulative hyperinsulinism (area of the plasma insulin curve after glucose IG: 642 +/- 120 vs 315 +/- 28 microU/ml/min and area after tolbutamide IT: 740 +/- 166 vs 335 +/- 35 microU/ml/min). No islet cell antibody was detected in the serum of MD patients. These results suggest that decrease of glucose tolerance is secondary to peripheral insulin resistance. Specific binding of insulin on erythrocytes was slightly but not significantly reduced in MD patients (specific binding: 8.21 +/- 0.9 vs 9.64 +/- 0.9%, receptor number: 23 +/- 2 receptors/cell, concentration of unlabelled insulin displacing 50% of the bound radioactivity: 7.2 +/- 0.56 vs 6.6 +/- 0.6 ng/ml). There was a loss of normal down regulation of insulin receptors in MD. The results of the euglycaemic glucose clamp confirmed the insulin resistance especially for the highest insulin infusion rates. These data show that the insulin resistance of MD is due to both receptor- and post receptor-defect but that the main abnormality is an unresponsiveness located after the insulin signal on the receptor.
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009136:Muscular Dystrophies / Q000503:physiopathology*; D011972:Receptor, Insulin / Q000032:analysis; D014044:Tolbutamide / Q000494:pharmacology
D001323:Autoantibodies; D001786:Blood Glucose; D007328:Insulin; C024211:islet cell antibody; D014044:Tolbutamide; D011972:Receptor, Insulin