Interleukin-1-beta, tumour necrosis factor-alpha, islet-cell antibody, and insulin secretion in children with thalassemia major on long term blood transfusion

Abstract

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.

Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test

“…Recently, several studies reported a long period of insulin resistance preceding overt diabetes mellitus in thalassaemic patients [4,7,9,10,13,21,23,27]. Because of the inverse relation between insulin sensitivity and insulin secretion, insulin resistance in patients at risk for type 2 diabetes mellitus is associated with hyperinsulinaemia.…”

Abnormal glucose tolerance in Egyptian beta-thalassemic patients: possible association with genotyping

“…Prevalence of diabetes among thalassemia patients has been reported to range from 2.3 to 24% (7–10). Although insulin deficiency, secondary to pancreatic islet iron deposition, has been considered the principle cause of the abnormalities in glucose metabolism observed in thalassemics (11–13), other studies have reported hyperinsulinemia with oral glucose tolerance testing, suggesting a role for insulin resistance in mediating these metabolic abnormalities (14, 15). Hemosiderosis, liver infections, and genetic factors seemed to be crucial in the development of diabetes (16, 17).…”

Increased Serum Heat Shock Protein 27 Antibody Titers and Prooxidant-Antioxidant Balance in Patients with Beta-Thalassemia Major

“…There is strong evidence of an association between endothelial cell activation and vascular complications in patients with β-thalassemia [6], whereas activation of the vascular endothelium is considered an important facet of inflammation, atherosclerosis [27,28,29], vasculitis and thrombosis [30,31,32,33,34,35,36]. However, the underlying mechanism of an association between immunomodulation and cardiovascular complications in these patients is not fully known.…”