Abstract. Background: During the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) with an oral glucose tolerance test (OGTT) using fasting (FPG) and 2-hour plasma glucose (2h-PG) samples has been recommended at 10, 12, 14, and 16 years and annually thereafter. A precise measurement of blood glucose (BG) concentration is the mainstay for an accurate diagnosis of dysglycemia, in order to limit the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis) results, especially in patients with BG values near the cut-off values. Research objective: The primary objective of our survey was to describe the procedures followed during the pre-analytical phase of screening for dysglycemia, based on the actual clinical practice of Centers following β-TDT patients. Answers from the survey were compared with international recommendations (American Diabetes Association and World Health Organization). Methods: This observational study was based on an online questionnaire survey. All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited. The questionnaire consisted of 6 sections and 22 questions, including single-choice, multiple-choice, and open-ended descriptive answers. Results: 14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and United Kingdom] accepted and completed the survey promoted by the ICET-A with a response rate of 77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 and 2,932 (86.9 %) were over the age of 10 years. The total number of thalassemia related diabetes mellitus (Th-RDM) reported by all Centers was 549. The total mean prevalence of Th-RDM was 14.7 ± 10.2 % . Generally, the survey has shown that there was a variable adherence to, and deviations from, current international guidelines. The lowest adherence rate regarded the information and instructions given to patients prior to OGTT (~56%), and how the BG samples were stored from the time of collection to time of centrifugation and analysis (~80 %). Differences in these factors may result in unintended variations in the prevalence of dysglycemia and have important implications for clinical practice. Conclusions: Many factors across the total testing process (sample collection, storage and transport during the preanalytical phase) can significantly impact OGTT accuracy and reproducibility, especially in patients with blood glucose values closer to the cut-off values. To minimize pre-analytical errors, a more precise diagnostic approach associated with closer patient follow-up is needed to reduce the risk of errors in glucose measurement.

Background:Over the last few decades, screening for dysglycemia in transfusion-dependent β-thalassemia patients (β-TDT) using an oral glucose tolerance test (OGTT) with fasting (FPG) and 2-hour plasma glucose (2h-PG) samples was recommended at 10, 12, 14, and 16 years, and annually thereafter. The precise measurement of PG levels is the mainstay for accurate diagnosis of dysglycemia and for limiting the risk of false-positive (i.e., overdiagnosis) and false-negative (i.e., underdiagnosis), especially in patients with PG values near the recommended cutoff values. Research objective:The primary objective of the survey was to describe the procedures of the preanalytical phase of screening for dysglycemia, using data from actual clinical practice at Centers caring for β-TDT patients. The collected data were compared to the international recommendations of the American Diabetes Association and the World Health Organization. Methods:This observational study was based primarily on an online questionnaire. All members of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) were officially invited to participate. The questionnaire consisted of 6 sections and 22 questions, with single-, multiple-choice, and open-ended descriptive answer options. Results:14 out of 18 invited Centers [Bulgaria, Cyprus, Greece, Iran (2), Italy (2), Oman, Qatar, Sri Lanka, Türkiye (3) and United Kingdom] accepted and completed the survey with a response rate of77.7 % The total number of β-TDT patients followed in the participating Centers was 3,372 with 2,932 (86.9 %)over the age of 10 years. A total of 549 patients were followed for thalassemia-related diabetes mellitus (Th-RDM). Furthermore, the survey across the 10 countries showed variable adherence to and deviations from current international guidelines. The lowest adherence rate was associated with the information and instructions given to patients prior to the OGTT and with how the blood samples were stored from collection to centrifugation and analysis. Differences in these factors may lead to unintended variations in the prevalence and severity of hyperglycemia, with important implications for clinical practice. To improve the quality of the pre-analytical phase across participating centers, the Standards for Reporting of Diagnostic Accuracy (STARD) statement was implemented. Conclusions:Based on the STARD statement, the pre-analytical blood sampling procedures for OGTT screening in thalassemia Centers require revision and standardization. To minimize preanalytical errors, a precise diagnostic approach, coupled with closer patient follow-up, is needed to reduce the risk of glucose measurement errors.

Background:Current guidelines for screening glucose dysregulation (GD) in patients with transfusion-dependent thalassemia (TDT) recommend an annual 2-hour oral glucose tolerance test (OGTT) starting at the age of 10 years. Objective:Assessment of adherence to OGTT screening in patients with TDT. Methods: A questionnaire was distributed to 18 Thalassemia Centers in 10 different countries, targeting factors influencing adherence to annual OGTT screening in specialized multidisciplinary pediatric and adult TDT units and identifying strategies to improve adherence to OGTT in TDT patients. Results:The mean reported percentage of all types of GD across 16 of the 18 centers at the last OGTT assessment was 32.0%, while the mean percentage for thalassemia-related diabetes mellitus (Th-RDM) was 12.2 +/- 9.7% (range: 0% -41%; median:13.2 %) in all participating centers. Notably, a high percentage of suboptimal or poor adherence to annual OGTT screening (mean 41.3%; range 10-90%) was reported by 17/18 centers. Poor adherence to annual OGTT among eligible patients was multifactorial and related to both patients and the healthcare system barriers. The most commonly suggested actionsby hematologists and endocrinologists for improving the adherence to OGTTwere flexibility in timing, easy approach to test location, improved collaboration among team members, and persistent reminding. Conclusions:Young adult patients with TDT are at high risk for developing GD and Th-RDM. Thus, annual screening with a 2-hour OGTT is recommended. Nevertheless, several patient barriers are associated with low adherence to annual OGTT. It is desirable to develop intensive initiatives to improve the screening rate for GD, while studies are warranted to update the current guidelines in TDT patients with low-risk factors for GD and for countries with low-resource settings

PURPOSE OF REVIEW:The aim of this short review is to provide an update on glucose homeostasis, insulin secretion and pharmacological management of osteoporosis in transfusion-dependent thalassemia (TDT).RECENT FINDINGS:A retrospective study, documenting the changes in glucose-insulin homeostasis from early childhood to young adulthood, has advanced our understanding of the evolution of glucose regulation in patients with TDT. Magnetic Resonance Imaging (T2* MRI) is considered to be a reliable tool to measure pancreatic iron overload. Continuous glucose monitoring systems (CGMS) can be used in early diagnosis of glucose dysregulation and in disease management in patients with already diagnosed diabetes. Oral glucose-lowering agents (GLAs) are effective and safe for the treatment of diabetes mellitus (DM) in patients with TDT, achieving adequate glycemic control for a substantial period of time. Current modalities for the management of osteoporosis in adults with TDT include inhibitors of bone remodeling such as bisphosphonates and denosumab as well as stimulators of bone formation (e.g., teriparatide), Considering the unique characteristics of osteoporosis associated with TDT, early diagnosis, treatment initiation and treatment duration are critical issues in the management this special population.CONCLUSIONS:Advances in the care of TDT patients  have led to improved survival and quality of life. Nevertheless, many chronic endocrine complications still remain. Their routine screening and a high index of suspicion are imperative in order to provide timely diagnosis and  treatment.