title: Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test.
abstract: Diabetes mellitus in patients with thalassaemia major is caused by secondary haemochromatosis due to transfusional iron overload. The pathogenetic mechanisms leading from siderosis to diabetes are still poorly understood. This study aimed at assessing the influence of insulin resistance and insulin deficiency on that process. Glucose, insulin and C-peptide levels during oral glucose tolerance tests (OGTT) from 36 thalassaemic patients with normal ( n=23), impaired ( n=6), or diabetic glucose tolerance ( n=7) and 32 control subjects were examined. Insulin secretion and insulin sensitivity were assessed by established calculated indices. Fasting, 2h and integrated glucose concentration were significantly increased in thalassaemic patients with normal glucose tolerance compared to controls (5.01/4.59 mmol/l, 6.33/5.17 mmol/l, and 844.2/739.3 mmol/l per min, respectively; all P<0.03). Patients with impaired glucose tolerance presented hyperinsulinaemia and delayed peak insulin during OGTT. The C-peptide/insulin ratio was decreased in patients with abnormal glucose tolerance compared to controls (5.85/7.33 x 10(3)pmol/l per min, P<0.03). It was negatively correlated with age in patients ( r=-0.45, P<0.01), but positively in controls ( r=0.43, P<0.03). Insulin sensitivity was significantly reduced in patients with impaired glucose tolerance or diabetes compared to controls. In addition, a significant decrease in patients with normal glucose tolerance was shown by two insulin sensitivity indices (all P<0.05). In thalassaemia patients, insulin sensitivity was negatively correlated with age. Insulin secretion capacity according to the homeostasis assessment model was significantly reduced in patient groups compared to controls (Kruskal-Wallis-test, P<0.004).
  
  
  CONCLUSIONS
  Insulin resistance is of central importance for the development of diabetes mellitus in patients with secondary haemochromatosis. An additional early defect in beta-cell secretion cannot be excluded.
authors.affiliation: Department of Paediatrics, University of Ulm, Prittwitzstrasse 43, 89075 , Ulm, Germany. holger.cario@medizin.uni-ulm.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Cario
authors.affiliation: ZIBMT, University of Ulm, Ulm, Germany.
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
authors.affiliation: Department of Paediatrics, University of Ulm, Prittwitzstrasse 43, 89075 , Ulm, Germany.
authors.forename: Klaus-Michael
authors.initials: KM
authors.lastname: Debatin
authors.affiliation: Department of Paediatrics, University of Ulm, Prittwitzstrasse 43, 89075 , Ulm, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kohne
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000209:etiology* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000172:deficiency / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D019190:Iron Overload / Q000150:complications*; D007515:Islets of Langerhans / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D018709:Statistics, Nonparametric; D017086:beta-Thalassemia / Q000150:complications*
chemical_list: D007328:Insulin