Long-Term Effects of Combined Chelation Therapy on Glucose Metabolism of Thalassemic Patients.

• The incidence of impaired glucose tolerance and diabetes in thalassemiamajor patients varied from 9% to 15%, depending on the age of assessment and intensity (and compliance) of chelation and transfusion. It is uncertain whether early assessment and tailored chelation can prevent diabetes and preserve pancreatic reserve. There are now reports of endocrine improvements with intense chelation in regards to glucose metabolism which are limited to 3 years of follow up. However, whether the pancreas may regenerate or remodel even with reduction in hemosiderosis is unknown and questions have arisen whether these are lasting improvements reflecting an overtime advantage earned by the intensification of chelation. The aim was to determine the long-term effects of combined chelation therapy on glucose metabolism in beta-thalassaemic patients • From January 2001 to October 2003, 42 thalassemic patients (initially treated with deferoxamine DFO monotherapy) were gradually switched to an individually tailored combined regimen with DFO and deferiprone. Glucose metabolism characteristics were evaluated by Oral glucose tolerance test (OGTT). Each patient was assessed separately before initiating combined therapy, and all patients were thereafter yearly reassessed (June 2005, June 2006 and June 2007). Full biochemical data (4 consecutive measurements) were available in 30 patients (3 got pregnant during this period, 5 denied repeated OGTT and 4 patients with severe and sustained hyperglycaemia started antidiabetic drugs after the second assessment in 2006). Insulin sensitivity and beta-cell function were assessed by calculated indices, using the most widely applied insulin sensitivity index - the homeostasis assessment model (ISI HOMA) which is based on fasting glucose and insulin alone. The area under the curve (AUC) was also calculated for estimating integrated response during OGTT for both glucose and insulin. Significant variations over time for each parameter were examined with ANOVA (general linear model) for repeated measurements. Ferritin levels were significantly decreased (P<0.01),AUCglu decreased (P=0.002)and SCHoma increased (P=0.004) as illustrated in Table 1. 70% of patients had abnormal glucose response during the first OGTT (diabetic response, Impaired glucose tolerance or impaired fasting glucose, according to the latest criteria of the American Diabetes Association published in September 2005). In May 2007, only 20% exhibited abnormal glucose response with the same provocative test (P<0.001,non-parametric McNemar test). Our 6-year follow-up demonstrates that use of combined chelation therapy continues to be of benefit in terms of glucose metabolism in thalassemic patients.