The mechanism of glucose intolerance in thyrotoxicosis was investigated in 119 patients with Graves's disease with careful consideration of the age-related deterioration of glucose tolerance. Before and after treatment of thyrotoxicosis with antithyroid drug, changes of blood glucose (BG) and serum immunoreactive insulin (IRI) in response to 50 g oral glucose tolerance test (OGTT) and insulin binding to red blood cell (RBC) were evaluated. In control subjects, the ΣIRI/ΣBG ratio after 50-g OGTT decreased progressively with age without significant change in absolute ΣIRI value, suggesting the occurrence of age-related insulin resistance. Glucose intolerance was much more apparent in hyperthyroid patients because of age-related relative decrease of insulin secretion. Such a decrease of insulin secretion was not found in age-matched postgastrectomy patients with a similar degree of hyperglycemia, however. Maximal binding of labeled insulin and number of insulin receptors of RBC were decreased in old patients but binding affinity was unchanged. Elevation of BG was partially suppressed when serum thyroxine (T4) and triiodothyronine (T3) were reduced to moderately supernormal levels, whereas ΣBG, ΣIRI, ΣIRI/ΣBG ratio, and insulin binding to RBC were all returned to normal when normal serum thyroid hormone concentration was maintained. Our data indicate that insufficient insulin secretion and reduced insulin action at the target cell are responsible, at least in large part, for age-related glucose intolerance in hyperthyroid patients.

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