INSULIN AND GLUCAGON-RESPONSES TO PROVOCATION WITH GLUCOSE AND ARGININE IN PREPUBERTAL CHILDREN WITH THALASSEMIA MAJOR BEFORE AND AFTER LONG-TERM BLOOD-TRANSFUSION

Hypertransfusion therapy has dramatically increased the duration and q uality of life in patients with B-thalassemia major; however, it leads to chronic iron overload, and is frequently complicated by the develo pment of diabetes mellitus or impaired glucose tolerance, To determine the early effect of iron overload on the endocrine pancreatic functio n, we studied glucose, insulin, and glucagon responses to oral load of glucose and to arginine provocation in 15 children with B-thalassemia major, before and after (3.1+/-0.6 years) high-transfusion and iron c helation and compared them with 15 age matched normal controls, In add ition, we evaluated growth hormone (GH) responses to oral clonidine an d measured the circulating insulin-like growth factor-I concentration in thalassemic children on long-term transfusion and controls. After l ong-term high-transfusion, thalassemic children had significantly decr eased serum insulin concentrations and low insulin/glucose ratios at 6 0 and 120 min after an oral glucose load (1.75 g/kg) in comparison wit h values before therapy and those for controls, None of the thalassemi c children had glucose intolerance after this period of frequent blood transfusion; however, their serum glucose levels at 60 and 120 min af ter the oral glucose load were significantly higher compared to contro l children, Thirty minutes after starting arginine infusion, serum ins ulin concentration was significantly lower in thalassemic children com pared to before therapy, Basal and arginine-stimulated glucagon secret ions were significantly elevated in thalassemic children on long-term blood transfusion with significantly low serum insulin/glucagon ratios , Ire addition, the high basal serum glucagon concentrations were not suppressed after the oral glucose load, Despite hyperglucagonaemia in all thalassemic children, their blood glucose dropped appropriately be low 50 per cent of the fasting glucose level after an intravenous insu lin dose (0.1 U/kg) ruling out any significant insulin-resistance. GH responses to clonidine provocation were subnormal in thalassemic child ren after long-term blood transfusion compared to controls, In summary , thalassemic children on long-term blood transfusion and iron chelati on have progressive and early loss of B-cell mass, manifested by decre ased insulin release in response to secretagogues, before the developm ent of significant insulin resistance or impairment of glucose toleran ce.