Clinical meaning
Hemoglobin A1C (glycated hemoglobin) measures the percentage of hemoglobin that has undergone non-enzymatic glycation by glucose, reflecting average blood glucose over the preceding 2-3 months (corresponding to the 120-day lifespan of red blood cells). The glycation reaction is irreversible and proportional to ambient glucose concentration: each 1% increase in A1C corresponds to approximately 1.6 mmol/L (29 mg/dL) increase in mean plasma glucose. The clinician interprets A1C in context: conditions causing falsely elevated A1C include iron deficiency anemia, splenectomy, alcoholism, and chronic kidney disease (carbamylated hemoglobin); conditions causing falsely low A1C include hemolytic anemias, blood loss, transfusion, pregnancy (hemodilution and increased RBC turnover), and hemoglobin variants (HbS, HbC, HbF). The ADA/CDA diagnostic threshold for diabetes is A1C 6.5% or greater; prediabetes is 6.0-6.4% (CDA) or 5.7-6.4% (ADA). Target A1C for most adults with diabetes is less than 7.0%, with individualization based on age, comorbidities, hypoglycemia risk, and life expectancy (tighter targets of less than 6.5% for younger patients with short disease duration and no cardiovascular disease; relaxed targets of less than 8.0-8.5% for elderly patients with multiple comorbidities, limited life expectancy, or hypoglycemia unawareness). The clinician uses A1C to guide treatment intensification, correlates with self-monitoring glucose data patterns, and addresses glycemic variability (time in range 70-180 mg/dL from continuous glucose monitoring is increasingly used alongside A1C for comprehensive glycemic assessment).