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.
Cario
Holger
H
Department of Pediatrics, University of Ulm, Germany. holger.cario@medizin.uni-ulm.de
Holl
Reinhard W
RW
Debatin
Klaus-Michael
KM
Kohne
Elisabeth
E
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005215:Fasting / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000097:blood*; D008099:Liver / Q000378:metabolism; D008297:Male; D011384:Proinsulin / Q000097:blood*; D011863:Radioimmunoassay; D017086:beta-Thalassemia / Q000097:blood*
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin; D007501:Iron