STUDIES ON THE CIRCULATING INSULIN INHIBITOR FOUND IN SOME DIABETIC PATIENTS EXHIBITING CHRONIC INSULIN RESISTANCE

Abstract

Serum from 2 of 10 cases of chronic insulin resistance was capable of inhibiting the effect of 0.2 unit of insulin in the rat hemidiaphragm assay. Using a more sensitive system, the fasted mouse, it was possible to detect insulin antagonist in 2 other cases where it could not be demonstrated with the hemidiaphragm preparation. In 9 of 10 cases studied there was an increased binding of insulin to insulin-binding protein as compared to insulin-sensitive diabetic patients. In some cases this gamma-globulin binding amounted to over 90% of 0.2 unit of insulin per ml of serum. In general there was good correlation between the amount of insulin binding and the demonstration of circulating insulin antagonist. Although the total serum gamma-globulin level was elevated in some cases, there was no particular relationship among these values, the daily insulin requirement, or the amount of insulin bound. In 1 patient, treatment with ACTH abolished the insulin resistance, and insulin antagonist, previously present, was no longer demonstrable. Contrary to expectations this therapy did not diminish the ability of the serum to bind large amounts of insulin. The insulin antagonist also inhibited human insulin. In contrast to the insulin antagonist associated with diabetic acidosis, the inhibitor in cases of chronic insulin resistance is not effective unless the hemidiaphragm, insulin and serum are all incubated simultaneously.