Factors Affecting HbA1c Measurements

Conditions That Shorten RBC Lifespan

Hemolytic anemia of any etiology falsely lowers HbA1c by reducing the time available for hemoglobin glycation, according to the American Diabetes Association 1, 3
Recovery from acute blood loss decreases mean RBC age, leading to spuriously low results, as reported by the American Diabetes Association 1, 2
Recent blood transfusion introduces younger donor red blood cells with less accumulated glycation, as noted by the American Diabetes Association 4, 3
Glucose-6-phosphate dehydrogenase (G6PD) deficiency increases red cell turnover and can lower HbA1c by approximately 0.8% in homozygous men and 0.7% in homozygous women, according to the American Diabetes Association 4, 3, 5

Erythropoietin therapy stimulates production of younger red blood cells with less accumulated glycation, as reported by the American Diabetes Association 4, 3, 5
Iron supplementation and vitamin B12 therapy increase erythrocyte production, introducing younger cells into circulation, according to the European Association for the Study of Diabetes 6

Second and third trimesters of pregnancy show slightly lower HbA1c levels due to increased red blood cell turnover, as noted by the American Diabetes Association 4, 7, 6

Sickle cell trait (HbS heterozygosity) in African Americans lowers HbA1c by approximately 0.3% for any given level of mean glycemia, according to the American Diabetes Association 4, 7, 3
Homozygous hemoglobin variants (HbSS, HbEE) prevent accurate HbA1c measurement entirely, as reported by the American Diabetes Association 1, 2

Vitamins C and E are reported to falsely lower HbA1c results, possibly by inhibiting glycation of hemoglobin, according to the American Diabetes Association 1, 2

Hemodialysis patients demonstrate discrepancies between HbA1c and true mean glycemia due to altered RBC turnover, as noted by the American Diabetes Association 4, 3

When HbA1c is unexpectedly low or discordant with plasma glucose measurements, use plasma glucose criteria alone for diagnosis and monitoring, as recommended by the American Diabetes Association 7, 5
Fructosamine or glycated albumin should be used when abnormalities in red blood cell turnover compromise HbA1c interpretation, though they reflect a shorter period (2-4 weeks) of average glycemia, according to the American Diabetes Association 1, 2, 5
Self-monitoring of blood glucose (SMBG) provides direct glucose measurements unaffected by RBC turnover, as noted by the American Diabetes Association 5
Continuous glucose monitoring (CGM) offers comprehensive glycemic assessment when available, according to the American Diabetes Association 5

Laboratories must use only NGSP-certified HbA1c assay methods traceable to the DCCT reference, as recommended by the American Diabetes Association 1, 7
Marked discrepancies between measured HbA1c and plasma glucose levels should prompt consideration that the assay may be unreliable for that individual, according to the American Diabetes Association 7
Boronate affinity chromatography methods may be more reliable in the presence of interfering factors, as noted by the American Diabetes Association 5