Interleukin-1-beta, tumour necrosis factor-alpha, islet-cell antibody, and insulin secretion in children with thalassemia major on long-term blood transfusion.
In vitro, cytokines like interleukin-1-beta (IL-1-B) and tumour necrosis factor-alpha (TNF-A) inhibit insulin release and can destroy islet B-cells. We measured blood levels of IL-1-B, TNF-A, and islet cell antibody (ICA) in 20 children with IDDM, 20 of their non-diabetic siblings, 20 children with thalassemia major on long-term hypertransfusion therapy and iron chelation, and 10 normal age-matched children. In the non-diabetic and thalassemic children we investigated the early phase of insulin release after i.v. glucose (0.5 g/kg, 30 per cent solution) and evaluated tolerance to oral glucose (1.75 g/ kg). Circulating IL-1-B and TNF-A concentrations were significantly higher in IDDM-siblings (33.7 +/- 12.7 pg/ml and 655 +/- 165 pg/ml, respectively) v. normal children (21.1 +/- 6.4 pg/ml and 383 +/- 122 pg/ml, respectively). Thalassemic children had no detectable circulating ICA. The prevalence of ICA was 30 per cent in children with IDDM and 60 per cent of their siblings. Impaired oral glucose tolerance was detected in five children with thalassemia (25 per cent), but in none of the IDDM-siblings. The early phase of insulin release was significantly depressed in thalassemic children (peak insulin = 29.2 +/- 5.1 mIU/ml) v. normal children (52.3 +/- 9.5 mIU/ml) and IDDM-siblings (45.3 +/- 12.4 mIU/ml). It appears that thalassemic children had significantly decreased insulin secretion and impaired glucose tolerance, however, the mechanism of B-cell dysfunction is not mediated by ICA nor by cytokines.
el Nawawy
A
A
Department of Pediatrics, College of Medicine, University of Alexandria, Egypt.
Soliman
A T
AT
el Azzouni
O
O
Abbassy
A A
AA
Massoud
M N
MN
Marzouk
S
S
Ibrahim
F
F
Helal
L
L
D000704:Analysis of Variance; D001323:Autoantibodies / Q000097:blood*; D001786:Blood Glucose / Q000032:analysis; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000097:blood*; D007515:Islets of Langerhans / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D017086:beta-Thalassemia / Q000150:complications* / Q000628:therapy
D001323:Autoantibodies; D001786:Blood Glucose; D007328:Insulin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha