Insulin delivery rate in response to glucose and arginine infusion in hyperthyroidism.

Insulin delivery rates were estimated from the peripheral serum insulin response to a single bolus injection of glucose or arginine in eight normal subjects and eight patients with hyperthyroidism. The mean rate constant for insulin disappearance was 0.2380 +/- 0.0052 per min in the control subjects, which was not significantly different from that observed in the patients with hyperthyroidism (0.2147 +/- 0.0111 per min). There were also no significant differences in the insulin response to glucose infusion (1.7 +/- 0.3 U during the first phase (0-10 min) and 5.6 +/- 1.6 U during the second phase (11-60 min) in normal subjects compared with 1.2 +/- 0.5 and 3.7 +/- 1.1 U respectively in the hyperthyroid patients). The delivered insulin in response to glucose infusion was similar in the two groups. The kg-value in the patients with hyperthyroidism was lower than that in the control subjects (1.24 +/- 0.11 versus 2.11 +/- 0.22; p less than 0.005). In hyperthyroidism, the low kg-value was not a result of the diminished insulin delivery to the general circulation. Insulin delivery showed a monophasic pattern following arginine infusion in both patients and control subjects. For the control subjects, the amount of insulin delivered was estimated to be 0.53 +/- 0.12 U during the first 10 min and 0.37 +/- 0.14 U during 11-30 min. In hyperthyroidism, the amount of insulin delivered was significantly lower than in the control subjects (0.21 +/- 0.06 U during the first 10 min and 0.07 +/- 0.03 U during 11-30 min). In the control subjects, the plasma glucose level was raised transiently following arginine infusion, but in hyperthyroidism, there was no change in plasma glucose levels. In hyperthyroidism, therefore, glucose intolerance appears to be primarily related to an antagonism of the hepatic effect of insulin by thyroxine rather than an inhibitory effect of thyroxine on insulin secretion. However, since delivery rate represents the measurement of peripheral serum insulin concentrations, these results cannot exclude an abnormality of hepatic insulin metabolism in hyperthyroidism.