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. Copyright (C) 2003 S. Karger AG, Basel.