Insulin Sensitivity and Exogenous Insulin Clearance in Graves' Disease: Measurement by the Glucose Clamp Technique and Continuous Indirect Calorimetry

Abstract

Insulin sensitivity was measured in a group of seven thyrotoxic patients and in a group of seven normal subjects by means of the glucose clamp technique. Infusion of insulin at a rate of 0.80 ± 0.05 mU/kg · min in the hyperthyroid patients and of 0.55 ± 0.04 mU/kg · min in the control group was performed to obtain a steady-state plasma insulin concentration of approximately 50 μU/ml. Substrate oxidation rates were measured in the postabsorptive state and during the 2 h of the clamp by means of continuous indirect calorimetry. In the postabsorptive state, hyperthyroid patients presented a preferential oxidation of lipids. During the period 60–120 min of the clamp, mean plasma glucose (92 ± 2 versus 93 ± 2 mg/dl), insulin (50 ± 5 versus 58 ± 3 μU/ml), and total glucose metabolism (5.8 ± 0.7 versus 6.1 ± 0.3 mg/kg - min) were similar in the hyperthyroid patients and the control subjects. The rate of glucose oxidation was higher in hyperthyroid patients than in control subjects (4.3 ± 0.5 versus 2.2 ± 0.2 mg/kg min, P < 0.001), while that of lipid oxidation was similar in both groups (0.6 ± 0.2 versus control 0.7 ± 0.1 mg/kg - min). The calculated metabolic clearance rate of insulin was markedly higher in the hyperthyroid patients (1144 ± 132 ml/min) than in the normal subjects (812 ± 56 mi/min, P < 0.025). It is concluded that insulin sensitivity is not altered in the thyrotoxic state. The major route of insulin-stimulated glucose disposal in the hyperthyroid patients appears to be glucose oxidation.