The Sickle Effect: The Silent Titan Affecting Glycated Hemoglobin Reliability.
Level 5 - mechanism / opinion, no new human data
Narrative review of observational literature without systematic methodology
PubMed 32923278 · doi:10.7759/cureus.9685
What was done
The authors conducted a traditional narrative review searching PubMed/MEDLINE and Google Scholar (keywords including sickle cell trait, HbAS, HbA1c, RBC lifespan, race, and genetics) to evaluate how sickle cell trait affects HbA1c interpretation and type 2 diabetes diagnosis.
What was found
The abstract reports no numerical data. It notes that studies evaluating NGSP-certified HbA1c methods with sickle cell trait (SCT) patients showed contrasting results. The largest study on red blood cell (RBC) lifespan in SCT showed a reduction in lifespan, though smaller studies contradicted this. The review also notes that individuals of African ancestry show higher baseline HbA1c than non-Hispanic whites and have higher prevalence of G6PD deficiency (which lowers HbA1c).
Why it matters
Because SCT and co-inherited conditions can alter red blood cell turnover and distort HbA1c readings, clinicians should consider combining HbA1c with alternate glycemic markers like fasting glucose, fructosamine, or glycated albumin to avoid missed or inaccurate diabetes diagnoses.
Limits
The paper is an unsystematic narrative review with no defined inclusion criteria, risk-of-bias assessment, or pooled sample size. The underlying evidence base consists mainly of observational studies with conflicting findings on assay interference and RBC lifespan.
Cited by
- supports Red blood cell disorders and variations in erythrocyte lifespan can alter hemoglobin A1c (HbA1c) readings.