A standard laboratory assay significantly underestimates blood sugar levels in people with sickle cell trait, potentially leading to widespread underdiagnosis of diabetes.
RT’s Three Key Takeaways:
- Assay Underestimation: A common laboratory assay used to measure blood sugar was found to significantly underestimate results in individuals with sickle cell trait compared to other testing methods.
- Underdiagnosis Risks: The discrepancy in testing methods led to a significant underclassification of pre-diabetes and a failure to detect diabetes in the study’s sickle cell trait group.
- Methodological Recommendations: Researchers advise healthcare providers to utilize laboratory methods that account for hemoglobin variants, such as high-performance liquid chromatography (HPLC), to ensure accurate diabetes assessments.
People with sickle cell trait may require specific laboratory monitoring for blood sugar to accurately detect pre-diabetes and diabetes, according to research presented at ADLM 2026.
Investigators found that immunoturbidimetry, a common laboratory assay used to measure protein concentrations, significantly underestimated hemoglobin A1c (HbA1c) levels in people with sickle cell trait when compared to high-performance liquid chromatography (HPLC). This discrepancy could lead to an underclassification of pre-diabetes and a failure to detect diabetes in these individuals.
“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,” said Elikem Kumahor, a specialist laboratory physician at Korle Bu Teaching Hospital in Accra, Ghana, in a news release.
Kumahor and colleagues conducted a retrospective study using 1,283 consecutive HbA1c tests from patients ages 18 and older at a tertiary hospital in early 2026. Initial measurements were performed on an HPLC platform that automatically detects hemoglobin variants, and 256 samples with suspected variants were reanalyzed using immunoturbidimetric assays.
The researchers categorized 1,027 patients as having normal hemoglobin and 198 as having the sickle cell trait. In the normal group, the mean HbA1c results showed minimal bias between the two laboratory methods. However, in the sickle cell trait group, the immunoassay significantly underestimated HbA1c compared to HPLC, showing a mean of 5.1% versus 5.9%.
The impact on patient classification was significant. Using the immunoassay, only 11.1% of participants with sickle cell trait were classified as pre-diabetic, compared to 34.5% when using HPLC. Furthermore, 4% of individuals with the trait met the criteria for diabetes using HPLC, while the immunoassay failed to classify any of those individuals as diabetic.
“HbA1c testing is currently being accessed by clinicians as a non-fasting glucose test for the diagnosis and monitoring of diabetes; however, its clinical utility may not be universally applicable in regions with a high prevalence of hemoglobin variants,” said Kumahor, a lead study author, in a news release.
Kumahor noted that individuals who are diabetic or routinely screened for the condition should have their hemoglobin genotype tested. He added that understanding these testing limitations can help guide healthcare protocols and policies in areas with high rates of sickle cell trait, such as West Africa.
Scientific poster session
Tuesday, July 28
9:30 a.m. – 5 p.m. (presenting authors in attendance from 1:30 – 2:30 p.m.)
The session will take place in the Poster Hall on the Expo show floor of the Anaheim Convention Center in Anaheim, California.
