Diagnostic Performance of HbA1c in Diabetes With Hemoglobinopathies: A Narrative Review and Update

Introduction: HbA1c is a widely used in diabetes mellitus, both for diagnosis and monitoring. However, the reliability of HbA1c can be significantly compromised by hemoglobinopathies, particularly thalassemia, and interfere with assay accuracy. This narrative review highlights the current evidence by comparing the accuracy of HbA1c measurements in diabetics with hemoglobinopathies.


Methods: Literature review was performed using Google Scholar, Embase, PubMed, Springer Nature Link, MDPI, and Taylor & Francis to identify studies comparing diagnostic performance of HbA1c in diabetics patients with & without thalassemia with quantitative glycemic markers measurement i.e. HbA1c, fructosamine, Glycalated Albumin (GA), Fasting Plasma Glucose (FPG) &/or Oral Glucose Tolerance Test (OGTT). Primary endpoint was diagnostic accuracy. Initially we identified 126 articles from January 2020 to June 2025. We identified 12 studies for review after including cross-sectional, cohort, comparative analytical, case control and retrospective studies. Also our inclusion criteria was studies measuring accuracy of glycemic markers between diabetic & non-diabetic patients with thalassemia, hemoglobin H & other hemoglobin variants. We exclude studies involving non-diabetic population, without comparison group, not assessing glycemic markers, conference abstracts, editorials, in-vitro, and non-English articles.


Results: A consistent trend showed that HbA1c values were significantly affected in hemoglobinopathies, leading to false positive or negative diagnoses. This diagnostic variability continue to show significant discrepancies in HbA1c among thalassemia patients when compared with more reliable fructosamine or Fasting Plasma Glucose (FPG) values. Interestingly, incidental discovery of hemoglobin variants through unexpected HbA1c readings, highlighting a clinical opportunity for early detection of underlying hematologic conditions. Overall, the findings strongly suggest that while HbA1c remains a cornerstone of diabetes diagnosis, its diagnostic accuracy is compromised in the presence of hemoglobinopathies.


Conclusions: Clinicians should exercise caution when interpreting hbA1c results in Thalassemia and other hemoglobinopathy patients. Alternative markers such as glycated albumin, fructosamine, FPG or OGTT should be considered.