A commonly used HbA1c immunoassay may fail to identify prediabetes and diabetes in people with sickle cell trait, raising concerns that some laboratories could be underdiagnosing the condition in populations where hemoglobin variants are common.
The findings, presented at the 2026 Association for Diagnostics & Laboratory Medicine (ADLM) annual meeting, compared an immunoturbidimetric HbA1c assay with high-performance liquid chromatography (HPLC) in more than 1,200 adults tested at a tertiary hospital in Accra, Ghana. The investigators found that the two methods produced similar results in people with normal hemoglobin but diverged substantially in those with sickle cell trait, with the immunoassay consistently reporting lower HbA1c values.
HbA1c is widely used because it reflects long-term blood glucose levels without requiring patients to fast. However, some testing methods cannot detect hemoglobin variants that may interfere with the measurement. In Ghana, where approximately 30 percent of the population carries sickle cell trait, understanding these analytical limitations is especially important for laboratories supporting diabetes diagnosis and monitoring.
The study found that the immunoassay classified far fewer people with sickle cell trait as having prediabetes than HPLC and did not identify any participants who met the diagnostic threshold for diabetes, whereas HPLC did. By contrast, results from the two methods were closely aligned in individuals without the trait.
Rather than highlighting the numerical differences alone, the findings point to a broader laboratory issue: assay selection can directly influence disease detection. HPLC platforms that recognize hemoglobin variants, or laboratory workflows that automatically perform confirmatory testing when variants are suspected, could reduce the risk of missed diagnoses in high-prevalence settings.
Lead researcher Elikem Kumahor said, “Our study indicates that relying on immunoassays alone likely contributes to a significant underdiagnosis of diabetes. We recommend adopting other laboratory methods that factor in hemoglobin variants, like HPLC or mandatory reflex testing algorithms, for accurate diabetes assessments in high-risk populations.”
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