Correction of Hyperinsulinemia by Glyburide Treatment in Nondiabetic Patients with Thalassemia Major

Abstract

ABSTRACT: Hyperinsulinemia and insulin resistance precede the development of diabetes in patients with thalassemia major on hypertransfusion/desferoxamine therapy. To examine whether these early metabolic defects could be reversed, seven nondiabetic patients with thalassemia (17 ± 4 y) were studied for 12 mo before and during 12 mo of low-dose treatment with glyburide (1.25 to 3.75 mg/d), a second-generation oral hypoglycemic agent. Plasma glucose responses to oral glucose (1.75 g/kg body weight) were normal before and after glyburide. Plasma insulin responses were markedly increased before glyburide therapy (area under insulin response curve 86 ± 15 and 96 ± 15 versus 40 ± 5 nmol/min/L in normal controls, p < 0.001). However, insulin responses to glucose fell significantly after 3 mo of glyburide (to 52 ± 7 nmol/min/L, p < 0.05 versus pretreatment) and were normalized after 12 mo (42 ± 7 nmol/min/L, p = NS versus controls). The rate of insulin-stimulated glucose metabolism during euglycemic insulin clamps (40 mU/m²/min) was low in the patients before treatment (163 ± 10 versus 215 ± 17 mg/m²/min in controls, p < 0.05) and increased to 205 ± 30 mg/m²/min after 3 mo of glyburide. The treatment was well tolerated. In conclusion, in nondiabetic, hyperinsulinemic, thalassemic patients, chronic glyburide therapy normalizes insulin responses to oral glucose. To the extent that insulin hypersecretion contributes to the development of diabetes in thalassemia, glyburide therapy may provide a means of postponing this complication of the disease.

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