Differential impact of glucose abnormalities and iron overload in TM (TM) and TI(TI): A comparative analysis of diagnostic approaches and management strategies for optimized care

Introduction: Thalassemia syndromes, specifically TM (TM) and TI(TI), are inherited blood disorders characterized by impaired hemoglobin synthesis, leading to chronic anemia. TM requires frequent blood transfusions, causing iron overload and elevating the risk for glucose metabolism issues, while TI, with fewer transfusions, experiences a lower incidence of these metabolic complications. Objectives: The review aims to compare glucose abnormalities, iron overload patterns, diagnostic approaches, iron chelation efficacy, and metabolic complications between TM and TI, offering insights into optimizing clinical management for each condition. Methods: A comprehensive literature review was conducted on studies from the past two decades, focusing on glucose metabolism, iron overload, and related complications in TM and TI patients. Data sources included PubMed, ScienceDirect, and Google Scholar, emphasizing studies that examined glucose abnormalities, iron accumulation, and treatment efficacy. Results: The findings indicate that TM patients have a higher prevalence of glucose abnormalities due to more severe iron overload, predominantly affecting pancreatic beta-cell function and insulin sensitivity. In contrast, TI patients generally exhibit milder metabolic complications due to less frequent transfusions and lower iron loads. Diagnostic tools like the Oral Glucose Tolerance Test (OGTT) and Continuous Glucose Monitoring (CGM) have been shown to detect early glucose abnormalities. Iron chelation therapy, critical for TM, is often more intensive, while TI patients benefit from intermittent chelation, effectively controlling iron without extensive intervention. Additionally, TM patients frequently require pharmacologic glycemic therapy, such as insulin or oral hypoglycemics, to manage more severe glucose dysregulation, whereas TI patients typically maintain stable glucose levels with lifestyle modifications. Discussion: TM and TI patients show distinct profiles in glucose dysregulation and iron overload. TM's high transfusion dependency results in rapid iron accumulation, necessitating aggressive iron chelation and regular glucose monitoring to mitigate the risk of diabetes. OGTT remains a viable option both for TM and TI. Individualized chelation strategies based on transfusion needs and iron levels are essential to minimize glucose-related complications, particularly in TM patients. Conclusions: TM patients experience higher and earlier glucose abnormalities compared to TI, primarily due to transfusion-induced iron overload. Personalized management involving intensive chelation, glucose monitoring, and lifestyle modifications can improve outcomes, especially in TM. For TI patients, milder chelation and lifestyle interventions suffice to maintain stable glucose levels. This review highlights the need for tailored approaches to address the unique challenges in glucose and iron management in TM and TI.