Effect of Enhanced Iron Chelation Therapy on Glucose Metabolism in Patients with β-Thalassaemia Major

Authors
Farmaki K, Angelopoulos N, Anagnostopoulos G, Gotsis E, Rombopoulos G, Tolis G.

Journal
British Journal of Haematology, 2006, 134, 438-444

Background
Endocrinopathies are the most common iron-induced complications in thalassaemia major (TM) patients. Recent data have indicated that deferiprone has greater ability than deferoxamine in chelating intra-cellular iron and in preventing iron-induced cardiac disease. No data are currently available on the effects of deferiprone on glucose metabolism in iron overloaded subjects. This study examines the effects of combining deferiprone (Ferriprox®) with deferoxamine (DFO) on the glucose metabolism in TM patients.


Methods

42 thalassaemia major patients, aged 8-42 years, previously maintained on DFO and without the diagnosis of diabetes mellitus were evaluated for glucose metabolism characteristics using oral glucose tolerance test (OGTT). Insulin sensitivity and beta-cell secretion were assessed according to the homeostasis assessment model (HOMA) and the insulin release index.

Each patient was individually assessed before initiating combined therapy and repeated measurements of the above parameters were taken to determine the effect of the combination treatment on glucose metabolism.


Results
Although iron deposition on pancreatic parenchyma seems to play a major role in the onset of diabetes, no link has been shown between the development of the disease and ferritin levels in long-term chelated patients. This indicates that additional factors, such as genetic susceptibility and insulin resistance, may also be important in its underling etiology. Combination therapy in this study resulted in significantly decreased fasting glucose as well as glucose response at all times during OGTT. A profound improvement in glucose disturbances was found in patients with impaired glucose tolerance and in patients with impaired fasting glucose. Several of these patients were in the Normal Glucose Tolerance group by the end of the study. Insulin secretion, according to the homeostasis assessment model, markedly increased in all groups, while overall reduction in insulin sensitivity did not reach statistical significance.

Conclusions
To the best of the author’s knowledge, this is the first study aimed at determining the effect of combination therapy on glucose metabolism in TM patients. While prospective studies are needed, this study highlights the roll that adequate chelation plays in preventing or improving glucose metabolism.

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