INSULIN-RESISTANCE IN TYPE-I DIABETES-MELLITUS - A MAJOR ROLE FOR REDUCED GLUCOSE EXTRACTION

We determined whether insulin resistance in Type I diabetes is caused by a defect in glucose extraction or blood flow and whether it is the rate of glucose metabolism rather than insulin that increases blood no w in these patients. To make this determination, 9 Type I diabetic pat ients (age 33 +/- 3 yr, body mass index 24 +/- 1 kg/m(2), HbA(1c) 8.3 +/- 0.1%) and 10 matched normal subjects were first studied under norm oglycemic hyperinsulinemic conditions. The diabetic patients were then restudied under similar conditions, but now whole body glucose uptake was normalized by glucose mass-action (glucose 8.7 +/- 0.6 mmol/L). D uring normoglycemia, rates of whole body (46 +/- 2 vs. 66 +/- 3 mu mol /kg . min, P < 0.001) and forearm (47 +/- 9 vs. 78 +/- 7 mu mol/kg for earm . min, P < 0.05) glucose uptake were decreased in the diabetic pa tients, because of a 32% decrease in the glucose AV-difference (1.5 +/ - 0.2 vs. 2.2 +/- 0.2 mmol/L, P < 0.05). Forearm blood now was similar in the diabetic patients (3.6 +/- 0.7 mL/dl . min) and normal subject s (3.7 +/- 0.3 mL/dL . min). During matched rates of whole body glucos e uptake (68 +/- 1 vs. 66 +/- 3 mu mol/kg . min, normoglycemic study i n controls us. hyperglycemic study in the diabetic patients), the gluc ose AV-difference across the forearm was 64% higher than during normog lycemia (2.4 +/- 0.3 us. 1.5 +/- 0.2 mmol/L, P < 0.05). Forearm blood flow (3.6 +/- 0.4 mL/dL . min) under conditions of matched glucose nux was similar to that during the normoglycemic study. We conclude that a defect in glucose extraction rather than blood now characterizes ins ulin resistance in uncomplicated Type I diabetes. The signal for the f low increase is insulin and not the rate of glucose metabolism.