Factors Contributing to Falsely Elevated HbA1c

Red Blood‑Cell‑Lifespan Disorders

• Iron‑deficiency anemia markedly raises HbA1c because prolonged red‑cell survival allows greater hemoglobin glycation; it is the most clinically significant cause of spurious elevation, together with other conditions that extend RBC lifespan such as aplastic anemia. (American Diabetes Association) 1
• Aplastic anemia and other disorders that slow erythropoiesis create an older erythrocyte cohort, leading to falsely high HbA1c independent of actual glycemia. (American Diabetes Association) 2

Assay‑Specific Interferences

• Chemically modified hemoglobin – carbamylated hemoglobin (seen in uremia) and acetylated hemoglobin (from high‑dose salicylates) can produce artifactual HbA1c increases in certain assay platforms. (American Diabetes Association) 2
• Metabolic disturbances such as hypertriglyceridemia, hyperbilirubinemia, chronic alcoholism, and opiate use have been reported to interfere with older HbA1c assay methods; these interferences are less relevant to modern standardized assays. (American Diabetes Association) 1
• Uremia‑related interference has been eliminated in current HbA1c assay technologies. (American Diabetes Association) 1

Hemoglobin Variants

• Hemoglobin S or C carrier status may yield spuriously high or low HbA1c values depending on the assay, particularly ion‑exchange HPLC where co‑elution occurs. (American Diabetes Association) 2
• Numerous hemoglobin variants (≈ 700 identified, most clinically silent) can cause unsuspected HbA1c measurement errors across different assay methods. (American Diabetes Association) 2

Physiologic Variables

• Age is associated with a modest HbA1c rise of about 0.1 % per decade after age 30, even in people without diabetes. (American Diabetes Association) 1
• Race/ethnicity influences HbA1c: on average, Black individuals have values ≈ 0.4 % higher than White individuals, a difference that does not alter the link between HbA1c and adverse outcomes. (American Diabetes Association) 1

Clinical Evaluation & Alternative Testing Strategies

• When to suspect interference:
  
  • Unexpectedly high or low HbA1c relative to glucose monitoring (e.g., self‑monitoring or CGM). (American Diabetes Association) 2
  • Abrupt HbA1c changes coinciding with a switch in laboratory assay method. (American Diabetes Association) 2
• Alternative assays:
  
  • Boronate‑affinity chromatography provides reliable HbA1c results in the presence of hemoglobin variants. (American Diabetes Association) 2
  • Glycated albumin or fructosamine reflect short‑term glycemia and are unaffected by red‑cell turnover or hemoglobin variants. (American Diabetes Association) 1

Laboratory Practice Recommendations

• Laboratories should recognize assay‑specific interferences—including hemoglobin variants—and select HbA1c measurement methods that minimize false elevations for the populations they serve. (American Diabetes Association) 1