CAN WE PREDICT INCIPIENT DIABETES MELLITUS IN PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA (β-TDT) REFERRED WITH A HISTORY OF PREDIABETES?

Background: Prediabetes and diabetes mellitus (DM) are complications in adult patients with transfusion dependent β-thalassemia (β-TDT), with their incidence increasing with age. Objective: This retrospective observational study describes the glycemic trajectories and evaluates predictive indices of β-cell function and insulin sensitivity/resistance in β-TDT patients with prediabetes, both in a steady state and during 3-h oral glucose tolerance test (OGTT), in order to identify patients at high risk for incipient diabetes. Setting: The study was mainly conducted at the Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara (Italy) in collaboration with thalassemia referring centers across Italy. Patients: The study included 11 β-TDT (aged 15.11- 31.10 years) with history of prediabetes. Methods: The ADA criteria for the diagnosis of glucose dysregulation were adopted. Investigations included evaluation of plasma glucose levels and insulin secretion, analysis of glycemic trajectories and indices of β-cell function and insulin sensitivity/resistance assessed in steady state and during OGTT. Results: The duration of progression from prediabetes to DM, expressed in years, showed a positive direct correlation with corrected insulin response (CIR-30 = r: 0.7606, P: 0.0065), insulinogenic index (IGI 0-120 = r: 0.6121, P:0.045), oral disposition index (oDI = r: 0.7119, P:0.013), insulin growth factor-1 (IGF-1= r: 0.6246, P: 0.039) and an inverse linear correlation with serum ferritin (SF = r: -0.7197, P: 0.012). Conclusions: Progressive β-cell failure, peripheral resistance to the action of insulin and reduction of oDI were the principal factors responsible for the progression from prediabetes to incipient DM

GLUCOSE HOMEOSTASIS AND ΑSSESSMENT OF Β-CELL FUNCTION BY 3-HOUR ORAL GLUCOSE TOLERANCE (OGTT) IN PATIENTS WITH Β-THALASSEMIA MAJOR WITH SERUM FERRITIN BELOW 1,000 NG/DL: RESULTS FROM A SINGLE ICET-A CENTRE

Aims: The primary aim of this study was to evaluate retrospectively the glucose homeostasis and surrogate indexes of insulin sensitivity and resistance, during a 3-hour oral glucose tolerance test (OGTT), in β- thalassemia major patients (β-TM) with serum ferritin (SF) below 1,000 ng/mL. Patients and methods: The retrospective cohort study evaluated the medical records of 24 β-ΤΜ patients from 2010 to 2022. Αt the year of study the mean age of patients was 31.0 ± 4.1 (20-37.11) years; 13 (54.1%) were females. The most commonly used iron chelator was deferoxamine (DFO: 75%), followed by deferiprone (DFP:12.5%) and deferasirox (DFX: 12.5%). Insulin sensitivity and resistance indexes were derived from OGTT. A liver iron concentration (LIC) < 3 mg/g d.w. and a global heart T2* value < 20 ms were considered as conservative cut-off values for insignificant iron overload (IOL). Results: The mean SF levels in the whole study cohort population at the age of evaluation was 549.6 ± 232.3 ng/mL. Based on the SF levels, two groups were identified: Group A (N = 14) < 500 ng/mL and Group B (N=10) 500-1,000 ng/mL.  Normal glucose tolerance (NGT) during OGTT was observed in 4 patients of Group A (28.5 %) and in 5 patients of Group B (50%) (P: 0.29). The remaining 15/24 patients (62.5%) had glucose dysregulation (GD). The mean age at starting iron chelation therapy (ICT) and the mean SF peak in Group A versus Group B were significantly higher in group Α.  The GD was  associated with significantly attenuated IGI (first phase of insulin response) and impaired oral disposition index (oDI). Hypogonadotropic hypogonadism (HH) was the most common associated endocrine complication in both groups of patients. Conclusions: This study showed that efficient iron chelation monotherapy in patients with β-TM and SF < 1,000 ng/ml did not entirely prevent glucose metabolism disorders, insulin secretion and sensitivity, and development of acquired hypogonadism

Heterozygosity of the Complex Corfu &delta;0&beta;+ Thalassemic Allele (HBD Deletion and HBB:c.92+5G&gt;A) Revisited

The Corfu &delta;0&beta;+ thalassemic allele is a unique thalassemic allele consisting of the simultaneous presence in cis of a deletion of the &delta;-globin (Hemoglobin Subunit Delta, HBD) and a single nucleotide variant in the &beta;-globin gene (Hemoglobin Subunit Beta, HBB). The allele has, so far, been described in individuals of Greek origin. The objectives of the study are to ascertain the prevalence of the Corfu &delta;0&beta;+ allele in comparison to other &beta;-thalassemia variants encountered in Greece using our in-house data repository of 2558 &beta;-thalassemia heterozygotes, and to evaluate the hematological phenotype of Corfu &delta;0&beta;+ heterozygotes in comparison to heterozygotes with the most common &beta;+- and deletion &alpha;0- thalassemia variants in Greece. The results of the study showed a relative incidence of heterozygotes with Corfu &delta;0&beta;+ at 1.56% of all &beta;-thalassemic alleles, and a distinct hematological phenotype of the heterozygotes characterized by microcytic, hypochromic anemia with normal levels of HbA2 (Hemoglobin A2) and elevated HbF (Hemoglobin F) levels. The application of a specific methodology for the identification of the Corfu &delta;0&beta;+ allele is important for precise prenatal and antenatal diagnosis programs in Greece

Deferasirox (Exjade (R)) in Pediatric Patients with beta-Thalassemia: Update of 4.7-Year Efficacy and Safety from Extension Studies

50th Annual Meeting of the American-Society-of-Hematology -- DEC 06-09, 2008 -- San Francisco, CAWOS: 000262104704490Amer Soc Hemato

3rd Pan-European Conference on Haemoglobinopathies and Rare Anaemias, 24-26 October 2012, Limassol - Cyprus

This abstract book contains all abstracts presented to the 3rd Pan-European Conference on Haemoglobinopathies and Rare Anaemias, 24-26 October 2012, Limassol - Cyprus

The Pancreatic changes affecting glucose homeostasis in transfusion dependent β- thalassemia (TDT): a short review.

BACKGROUND: The natural history of the glycometabolic state in transfusion-dependent β-thalassemia (TDT) patients is characterized by a deterioration of glucose tolerance over time. AIMS: This review depicts our current knowledges on the complex and multifacet pathophysiologic mechanisms implicated in the development of alteration of glucose homeostasis in patients with TDT. SEARCH STRATEGY: A systematic search was done on December 2020 including Web of Science (ISI), Scopus,  PubMed, Embase, and Scholar for papers published in the last 20 years. Moreover, we checked the reference lists of the relevant articles and previously performed reviews for additional pertinent studies. The personal experience on the care of patients with thalassemias is also reported. CONCLUSION: A regular packed red blood cells (PRBCs) transfusion program, optimization of chelation therapy, and prevention and treatment of liver infections are critical to achieve adequate glucometabolic control in TDT patients. Many exciting opportunities remain for further research and therapeutic development