MON-601 - HbA1c Cut-Off of 6.5% Is Unsuitable for the Diagnosis of Diabetes in A South Asian Population

Introduction: An HbA1c value ≥ 6.5% is sufficient to make a diagnosis of diabetes according to the American Diabetes Association (ADA) guidelines. It is known that this is inaccurate for persons of African and South Asian descent. It is common for many persons not known to have diabetes to measure their HbA1c in a ‘package’ of tests. We have anecdotally noted that some persons with HbA1c ≥ 6.5% do not have diabetes when their FPG and 2hr PPPG are measured. We did a pilot study to see if a HbA1c of 6.5% is suitable for the diagnosis of diabetes in a South Asian population.
Material: 297 persons who had blood tests in our laboratory between February 2024 and December 2025 had their blood tested for fasting glucose and HbA1c. 128 had FPG under 7 mmol/l and were not known to have diabetes. All the subjects had RBC lifespan studies done using Levitts’ CO breath test. HbA1c was measured by Ion exchange HPLC (manufacturer, BIORAD Laboratories, USA). Hb-F < 10%, labile A1c, carbamylated hemoglobin < 4.0 %, Hb E and Hb S traits did not interfere with HbA1c measurement. All subjects had normal G6PD and were not thalassemia carriers. The study was approved by the local Ethics Committee.

Results: Persons (n=128) with FPG under 7 mmol/l had a median HbA1c of 5.9 %. The range was 4.1% - 9.1%, the interquartile range was1.0 and values were not normally distributed. 32 persons had FPG < 7 mmol/l with HbA1c ≥ 6.5 % and would have been wrongly diagnosed to have diabetes by ADA criteria. Bland Altman plots showed good linearity between FPG and HbA1c, showing internal consistency of the data.
Fig 1: Showing the relationship between FPG and HbA1c in persons without diabetes

RBC lifespan studies showed no correlation between diabetes and RBC survival. Median RBC survival was 89 days (range, 59-169 days). RBC survival was not normally distributed; it was skewed to the left.

Discussion: Our data showed poor correlation between FPG and HbA1c around the diagnostic cut-off of 6.5%, while individual pairs of values showed good consistency in the Bland Altman test. Some subjects could have the alpha thalassemia trait which reduce RBC lifespan and interfere with HbA1c measurements . This trait is not generally measured. RBC lifespan has been historically calculated using various radio pharmaceuticals. Recent data on RBC lifespan using the simple hand-held CO monitor have given results like ours, in that they show a shorter median RBC lifespan and a large spread. A wide variation in RBC life span with more subjects showing shorter lifespan has the potential to affect HbA1c measurement. This casts doubt on the reliability of HbA1c as a diagnostic tool in diabetes.

Conclusions: HbA1c values ≥ 6.5% is not appropriate for the diagnosis of diabetes in a South Asian population due in part to a wide variability in RBC lifespan.

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