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Background: The global prevalence of diabetes mellitus has been growing in recent decades and the complications of longstanding type 2 diabetes continue to place a burden on healthcare systems. The hemoglobin A1c (Hb A1c) content of the blood is used to assess an individual's degree of glycemic control averaged over 2 to 3 months. In the USA, diabetes is the seventh leading cause of death. Black, indigenous, people of color (BIPOC) are disproportionately affected by diabetes compared to non-Hispanic whites. There are many reports of interaction of Hb A1c and hematologic conditions that have a high prevalence in the Black population; some of these effects are contradictory and not easily explained. This review attempts to document and categorize these apparently disparate effects and to assess any clinical impact., Methods: Hb A1C can be determined by a variety of techniques including cation-exchange chromatography, electrophoresis, immunoassays, and affinity chromatography. The amount of Hb A1c present in a patient specimen depends not only on blood glucose but is strongly influenced by erythrocyte survival and by structural variations in the globin chains. Sickling hemoglobinopathies are well-represented in the USA in African Americans and the effects of these hemoglobin disorders as well as G6PD deficiency is examined., Conclusion: Hb A1c measurement should always be performed with a cautious approach. The laboratory scientist should be aware of possible pitfalls in unquestioningly determining Hb A1c without a consideration of hematologic factors, both inherited and acquired. This presents a challenge as often times, the laboratory is not aware of the patient's race., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)