Hemoglobinopathies and diabetes mellitus: from pathophysiology to clinical practice

Hemoglobinopathies, primarily β-thalassemia and sickle cell disease (SCD), represent a major global health burden. With extended lifespans, secondary diabetes mellitus (DM) has emerged as a frequent endocrine complication. This review examines the underlying pathophysiology, diagnostic pitfalls, and therapeutic strategies for this distinct population. A narrative review was performed using PubMed database, including English full-text articles published up to July 2026. The pathogenesis of DM in hemoglobinopathies involves a duality of iron-mediated β-cell apoptosis and hemolysis-driven hepatic and peripheral insulin resistance. HbA1c is often inaccurate due to method-specific analytical interference, as well as biological distortion driven by shortened erythrocyte survival and blood transfusions. Consequently, formal screening and diagnosis must rely on plasma glucose criteria, primarily fasting plasma glucose and the oral glucose tolerance test (OGTT). Meanwhile, Continuous Glucose Monitoring (CGM) metrics serve as valuable tools for glycemic monitoring and treatment optimization. Basal-bolus insulin remains the cornerstone for DM and emerging cardiorenal protective agents (SGLT-2 inhibitors and GLP-1 receptor agonists) represent promising adjuncts, while intensive iron chelation therapy can reverse early-stage dysglycemia when initiated prior to irreversible β-cell damage. Implementing dedicated, multidisciplinary specialized care centers co-led by hemoglobinopathy specialists and diabetologists is essential to optimize long-term adult outcomes.