Falsely Elevated A1C
“Any condition that prolongs the life of the erythrocyte or is associated with decreased red cell turnover exposes the cell to glucose for a longer period of time, resulting in higher A1c levels. Iron deficiency anemia is a commonly reported condition associated with falsely elevated A1c. Studies in patients with and without diabetes have demonstrated that treatment of iron deficiency anemia lowers A1c, although the exact mechanism remains unclear. Other conditions associated with decreased red cell turnover are also associated with falsely elevated A1c including vitamin B-12 and folate deficiency anemias, and asplenia. ” J Gen Intern Med. 2014 Feb; 29(2): 388–394.
Falsely Lowered A1c
“Similarly, any condition that shortens the life of the erythrocyte or is associated with increased red cell turnover shortens the exposure of the cell to glucose, resulting in lower A1c levels. Conditions such as acute and chronic blood loss, hemolytic anemia, and splenomegaly can all cause falsely lowered A1c results.
Patients with end-stage renal disease generally have falsely low A1c values. This is primarily due to the associated chronic anemia with decreased red cell survival” J Gen Intern Med. 2014 Feb; 29(2): 388–394.
Conditions Associated with Falsely Elevated or Lowered A1c
This table is from J Gen Intern Med. 2014 Feb; 29(2): 388–394.
| Condition | Effect on A1c | Comments |
|---|---|---|
| Anemias associated with decreased red cell turnover [If you’re not making enough new RBCs, there are not enough young people entering the workforce and the retirement age is increased meaning that elderly people have to work till later in their old age] |
False Increase | I.e., iron deficiency anemia, anemia from vitamin B-12 or folate deficiency *Also, Aplastic Anemia |
| Asplenia / Splenectomy [The spleen normally takes damaged or worn-out RBCs out of service] | False Increase | Increased erythrocyte lifespan |
| Uremia / Renal failure | False Increase | Formation and detection of carbamyl-hemoglobin |
| Severe hypertriglyceridemia | False Increase | When level >1,750 mg/dL |
| Severe hyperbilirubinemia | False Increase | When level >20 mg/dL |
| Chronic alcohol consumption | False Increase | Formation of acetaldehyde-HbA1 compound |
| Chronic salicylate ingestion | False Increase | Mechanism uncertain, may interfere with assay |
| Chronic opioid ingestion | False Increase | Mechanism uncertain |
| Lead poisoning | False Increase | Mechanism uncertain |
| Anemia from acute or chronic blood loss. | False Decrease | Includes hemolytic anemia |
| Splenomegaly | False Decrease | Decreased erythrocyte lifespan |
| Pregnancy* | False Decrease | Decreased erythrocyte lifespan |
| Vitamin E ingestion | False Decrease | Reduced glycation |
| Ribavirin and interferon-alpha | False Decrease | Possibly due to hemolytic anemia |
| Red blood cell transfusion† | False Increase or False Decrease | High glucose concentration in storage medium (False Increase) Dilutional effect (False Decrease) |
| Hemoglobin variants | False Increase or False Decrease | Depends on method and assay used A1c generally reliable for heterozygous variants, but not homozygous variants (See Table 3) |
| Vitamin C ingestion | False Increase or False Decrease | May increase A1c when measured by electrophoresis May decrease levels when measured by chromatography due to competitive inhibition of glycosylation |
*Expect falsely low A1c values through the 2nd trimester, but may rise during the 3rd trimester.
Typically reported to falsely elevate A1c, but may also result in false decrease.
References / Further Reading
Radin MS. Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading. Journal of General Internal Medicine. 2014;29(2):388-394. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912281/
Am Fam Physician. 2016 Jan 15;93(2):103-109.Diabetes Mellitus: Screening and Diagnosis. https://www.aafp.org/afp/2016/0115/p103.html