Disproportionately Elevated Fasting Proinsulin Levels in Normoglycemic Patients with Thalassemia major Are Correlated to the Degree of Iron Overload

OBJECTIVE: To analyze the secretion of the insulin precursor proinsulin in patients with beta-thalassemia and its possible relation to iron overload. METHODS: We assessed fasting proinsulin, insulin, C-peptide and glucose levels from 34 patients with beta-thalassemia and 33 healthy controls. The correlation to age, body mass index, hepatic iron concentration, serum ferritin and serum AST was analyzed. RESULTS: Fasting proinsulin (p < 0.002) and proinsulin-to-insulin ratio (p < 0.02) were significantly increased in patients with thalassemia irrespective of the degree of glucose tolerance. They correlated positively to serum ferritin, liver iron, patient age and serum AST (all p < 0.05). CONCLUSIONS: Disproportionately elevated proinsulin levels in thalassemic patients indicate early beta-cell dysfunction due to siderosis. An additional biological significance of hyperproinsulinemia and its possible ability to predict long-term iron toxicity in these patients remain to be clarified.