Discordantly Low HbA1c in Patients Receiving Dapsone: Prevalence and Associations with Hemolysis and...

Glycosylated hemoglobin (HbA1c) is widely used for the diagnosis and long-term monitoring of diabetes mellitus (DM). However, its accuracy may be compromised by conditions and medications that alter erythrocyte lifespan or hemoglobin structure. Dapsone, commonly used in the treatment of Hansen's disease, has been reported to cause spuriously low HbA1c values, but systematic data on its prevalence and underlying mechanisms remain limited.

The objectives of this study were to (1) determine the prevalence of discordantly low HbA1c levels in patients receiving dapsone therapy, including individuals with and without DM; (2) explore associations between discordant HbA1c and markers of hemolysis and methemoglobinemia; and (3) compare measured HbA1c values obtained by high-performance liquid chromatography (HPLC) with expected HbA1c values derived from fructosamine using the glycosyl gap.

This retrospective cross-sectional study included 30 patients receiving oral dapsone for Hansen's disease and 10 healthy controls. HbA1c was measured using ion-exchange HPLC and compared with expected HbA1c values calculated from serum fructosamine. Parameters related to hemolysis and methemoglobinemia were assessed. Discordant HbA1c was defined by a negative glycosyl gap. Subgroup analyses were exploratory.

Among patients receiving dapsone, 16 had DM and 14 were normoglycemic. Discordantly low HbA1c was observed in 27 of 30 patients (90%), including 15 of 16 patients with DM and 12 of 14 without diabetes. Markers of hemolysis and methemoglobinemia showed trends consistent with biological plausibility but did not demonstrate statistically significant differences sufficient to establish causality.

A high prevalence of discordantly low HbA1c was observed among patients receiving dapsone therapy, highlighting an important clinical pitfall in the interpretation of HbA1c. While hemolysis and methemoglobinemia remain biologically plausible contributors, these findings should be considered hypothesis-generating. Clinicians should exercise caution when interpreting HbA1c in patients treated with dapsone and consider alternative glycemic markers such as fructosamine.