Diabetes is an important problem encountered in thalassemic patients. The severity and type of glucose disturbances vary greatly in different studies. Also the pathogenesis seems to be complex; either insulin deficiency or insulin resistance may mediate the glucose disturbances. In a group of thalassemic patients glucose homeostasis was evaluated. Diabetes prevalence was 1.8%. Forty patients were investigated both with an oral glucose tolerance test and first-phase insulin response. Three patients had impaired fasting glucose, 1 patient had impaired glucose tolerance, and 2 patients had hyperinsulinism. Nineteen of 40 patients who were tested had low first-phase insulin response (47.5%) with below 10th centile. Age, BMI, height SDS, age at diagnosis, age at first blood transfusion, number of blood transfusions in a year, percentage of elevated liver enzyme, and hemoglobin and ferritin levels were not different between patients with low first-phase insulin response to patients with normal first-phase insulin response. Four patients are HCV infected, and only 1 of them had low first-phase insulin response. The study group showed a high rate of impairement in insulin secretion by first-phase insulin response to glucose overload, despite the low rate of insulin resistance. Defect of insulin secretion in thalassemic patients may develop earlier than insulin resistance, and then be accompanied by insulin resistance. Increasing insulin resistance with age and the occurrence of additional factors could lead to detoriation of glucose metabolism.