Can G6PD deficiency make HbA1c underestimate diabetes?

Yes. G6PD deficiency can shorten red-cell survival, leaving less time for hemoglobin to become glycated. In cohort data, HbA1c was substantially lower at the same glucose level, particularly in men with G6PD deficiency. This can delay diagnosis or make diabetes appear better controlled than it is. Individual interpretation should combine clinical context with glucose-based or other appropriate measurements.

Bottom line: HbA1c is not equally reliable in every biological context. A result should not be reinterpreted or a treatment changed without a clinician who knows the person’s history and laboratory data.

Why red-cell lifespan matters

HbA1c estimates recent glycemic exposure by measuring the proportion of hemoglobin that has become glycated. If red blood cells are removed from circulation earlier, the average cell has had less time to accumulate glucose. The HbA1c can therefore look lower even when fasting or average glucose is high.

G6PD deficiency is X-linked. Men usually have one X chromosome, so a pathogenic variant can affect a large share of their red cells. Women may have a mosaic population of affected and unaffected cells, producing more variable effects.

What the studies found

Nationwide longitudinal records were used to compare people with G6PD deficiency and matched controls over many years. At comparable glucose levels, HbA1c values were shifted downward in the G6PD-deficient group. The discrepancy increased at higher glucose levels and was particularly marked among men.

A New England Journal of Medicine report concluded that HbA1c markedly underestimated glucose levels in this population. A subsequent analysis described delayed treatment and greater complications, raising concern that a universally applied threshold can create inequity.

What this means in practice

The finding does not make HbA1c useless, and it does not supply one corrected threshold for every person. It means clinicians may need to interpret HbA1c alongside fasting glucose, continuous glucose monitoring, fructosamine, glycated albumin, symptoms, and the individual’s clinical context.

The appropriate alternative depends on the person, laboratory access, comorbidities, and the clinical decision being made.

Important limitations

These analyses were observational and based on routine records. Treatment access is influenced by many clinical and social factors. G6PD variants and degrees of enzyme activity differ across populations, so the size of the HbA1c effect is not identical for everyone.

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