title: Disproportionately elevated fasting proinsulin levels in normoglycemic patients with thalassemia major are correlated to the degree of iron overload.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Ulm, Germany. holger.cario@medizin.uni-ulm.de
authors.forename: Holger
authors.initials: H
authors.lastname: Cario
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kohne
mesh_terms: 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*
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D011384:Proinsulin; D007501:Iron