Conditions That Falsely Elevate A1C

Introduction to Falsely Elevated A1C Conditions

Iron deficiency anemia is the most clinically significant condition that falsely elevates A1C levels, while chronic kidney disease with uremia can also cause false elevation through hemoglobin carbamylation, according to the American Diabetes Association 1, 2, 3

Iron deficiency anemia prolongs erythrocyte lifespan and exposes red blood cells to glucose for longer periods, causing falsely elevated HbA1c levels, which is one of the most common causes of falsely elevated A1C in clinical practice 3
The American Diabetes Association specifically identifies iron-deficient anemia as making A1C less reliable than blood glucose measurement, and it should be suspected when A1C is discordant with glucose monitoring 1, 3
Carbamylation of hemoglobin in uremic patients can cause falsely increased A1C values, but this effect is method-dependent and may not occur with all assay types, as noted by the American Journal of Kidney Diseases 2
Advanced CKD can falsely elevate A1C through carbamylation, but it can also falsely lower A1C through shortened red blood cell lifespan and hemolysis, making interpretation complex, according to the American Journal of Kidney Diseases and the American Diabetes Association 2, 3

Hemoglobin variants (HbS, HbC) can result in falsely elevated or falsely lowered HbA1c levels depending on the specific assay method used, and marked discrepancies between measured A1C and plasma glucose levels should prompt consideration that the A1C assay may not be reliable for that individual, as stated by the American Diabetes Association 1, 3

African Americans may have higher A1C levels than non-Hispanic Whites with similar fasting and postglucose load glucose levels, and African Americans with prediabetes have HbA1c values that are 0.4% higher than white persons for any given level of glycemia, according to the American Diabetes Association 1, 3
However, African Americans heterozygous for HbS (sickle cell trait) may have lower A1C by about 0.3% compared with those without the trait, as noted by the American Diabetes Association 1, 4

A1C is surprisingly high or significantly changed coincident with a change in laboratory method, discrepancy between A1C and self-monitored blood glucose readings, or A1C does not correlate with patient's symptoms or clinical presentation, should prompt further investigation, including obtaining complete blood count to assess for anemia and ordering iron studies to evaluate for iron deficiency, as recommended by the American Diabetes Association and Praxis Medical Insights 1, 3
Consider erythrocyte creatine measurement to assess red blood cell lifespan if available, and use fructosamine or glycated albumin when A1C reliability is questioned, though these reflect a shorter period of average glycemia than HbA1c, according to Praxis Medical Insights 3
Consider continuous glucose monitoring (CGM) to better understand glycemic patterns, and use plasma glucose criteria exclusively for diagnosis in patients with conditions affecting red blood cell turnover, as stated by the American Diabetes Association and Praxis Medical Insights 1, 3, 5

Never base treatment decisions solely on a single HbA1c measurement without consideration of glucose monitoring results, as this may lead to unnecessary initiation or intensification of therapy, and do not use A1C for diagnosis in conditions with increased red blood cell turnover, according to the American Diabetes Association and Praxis Medical Insights 1, 3