Why A1C Can Be Wrong: Conditions That Affect Accuracy

A1C assumes your red blood cells behave in a fairly typical way. When that assumption breaks, the number can be meaningfully wrong, and most people never find out why.

By Charles Kirkland, Founder, Metabolic Clarity Labs
Updated August 2026

Quick answer: A1C can read falsely high or falsely low when something changes how long red blood cells survive or how hemoglobin behaves. NIDDK identifies iron-deficiency anemia, kidney failure, and liver disease as causes of falsely high results, while hemoglobin variants common in people of African, Mediterranean, or Southeast Asian descent can make the test unreliable in either direction. Blood transfusion, recent major blood loss, and pregnancy can also distort the number. The clue clinicians look for is a mismatch between your A1C and your actual glucose readings or symptoms.

The mechanism behind every A1C error

A1C works by measuring how much glucose has attached to hemoglobin over the roughly 120-day lifespan of a red blood cell. That means the test has a built-in assumption: your red blood cells live for about the expected amount of time, giving glucose a fairly consistent window to attach.

When something shortens that window, cells spend less time exposed to glucose, and the result reads falsely low. When something lengthens it, or increases the exposure some other way, the result reads falsely high. Nearly every source of A1C inaccuracy traces back to this same underlying mechanism.

What can make A1C read falsely high

According to NIDDK, a falsely high A1C result can occur in people who are very low in iron, including those with iron-deficiency anemia. Kidney failure and liver disease are also identified as causes of false results.

The kidney disease mechanism is worth understanding specifically because it can work in more than one direction. When kidneys begin to fail, they lose some ability to clear acids that build up in the body. That buildup, called metabolic acidosis, can speed up the rate at which glucose binds to hemoglobin, pushing A1C higher than actual glucose exposure would suggest. At the same time, kidney disease can also reduce red blood cell production, causing anemia that pulls the number in the opposite direction. The net effect on any individual person's A1C depends on which mechanism dominates.

What can make A1C read falsely low

Anything that shortens red blood cell survival tends to push A1C down. This includes hemolytic anemia, recent significant blood loss, and blood transfusion, since transfused cells haven't been exposed to your glucose levels for the same length of time as your own older cells. Some kidney disease treatments, including certain medications and erythropoiesis-stimulating agents used to manage anemia in kidney disease, can also lower A1C independent of actual glucose control.

Pregnancy is its own category. A1C tends to run lower during the second and third trimester due to changes in red blood cell turnover, which is part of why A1C is not the standard test used to diagnose gestational diabetes.

Hemoglobin variants: the one most people have never heard of

This is a genuinely underappreciated source of A1C error. NIDDK specifically notes that people of African, Mediterranean, or Southeast Asian descent, or those with family members who have sickle cell anemia or thalassemia, may carry a hemoglobin variant that can interfere with some A1C tests, making the result unreliable in either direction depending on the specific variant and the laboratory method used.

The genuinely tricky part: most people with a hemoglobin variant have no symptoms and have no idea they carry it. The four most common variants, in order of worldwide prevalence, are hemoglobin S, E, C, and D. Someone can carry one of these in a form that causes no disease and never gets tested for it, simply because there's ordinarily no clinical reason to look.

The practical clue: when your A1C doesn't match your glucose

Clinicians typically suspect A1C interference when the A1C result and blood glucose readings, whether from a meter, a continuous glucose monitor, or fasting plasma glucose, don't agree with each other. If your A1C suggests one story and your actual measured glucose tells a different one, that mismatch is worth raising directly rather than assuming the more alarming number must be correct.

Medications can factor in too. Certain immunosuppressants, high-dose vitamin C or vitamin E, and some other drugs and supplements have been associated with interference in specific A1C assay methods.

What to actually do if you suspect this applies to you

Mention your family background and any known anemia, kidney disease, or liver disease when discussing A1C results with your clinician, even if it hasn't come up before.

If your A1C and your home glucose readings consistently disagree, say so specifically rather than assuming one of them is simply wrong.

Ask whether a hemoglobin variant panel, a different A1C assay method, or an alternative test like fructosamine or glycated albumin would add useful clarity in your specific case.

Don't attempt to self-diagnose a hemoglobin variant or kidney-related interference from an online description; this requires laboratory testing and clinical interpretation.

If you're pregnant, follow the pregnancy-specific glucose testing protocol your obstetric team provides rather than relying on a standard A1C result.

Frequently asked questions

Can anemia make my A1C wrong?

Yes, in either direction depending on the type. Iron-deficiency anemia is specifically identified as a cause of falsely high results, while hemolytic anemia and other conditions that shorten red blood cell survival tend to cause falsely low results.

How would I know if I have a hemoglobin variant?

Most people don't know unless it's specifically tested for, since carriers are frequently symptom-free. A blood test can detect hemoglobin variants; this is worth discussing with your clinician if your A1C and glucose results don't match, or if you have a relevant family or ethnic background.

Does kidney disease always make A1C too high or too low?

It can go either direction, since kidney disease can simultaneously push A1C up through metabolic acidosis and down through anemia and reduced red blood cell production. The net effect varies by individual.

Should I get an A1C test if I just had a blood transfusion?

A recent transfusion can distort A1C for a period of time. If you've had one recently, mention it before A1C testing so your clinician can interpret the result appropriately or consider an alternative test.

Is there a better test if A1C isn't reliable for me?

Depending on the situation, your clinician might use fasting plasma glucose, an oral glucose tolerance test, fructosamine, or glycated albumin, each of which reflects a different, generally shorter window than A1C's roughly three-month average.

The Metabolic Clarity takeaway

A1C is a genuinely useful test built on an assumption most people never think to question: that their red blood cells behave typically. When that assumption doesn't hold, whether from anemia, kidney or liver disease, a hemoglobin variant, or pregnancy, the number can be meaningfully off in either direction. The fix isn't to distrust A1C generally; it's to flag the mismatch when your glucose readings and your A1C tell different stories.

Next step: Read the complete guide to A1C for the full picture of what the test measures, then mention any relevant family background or medical history at your next A1C discussion.

Sources

• NIDDK, The A1C Test and Diabetes
• NIDDK, Interpreting A1C: Diabetes and Hemoglobin Variants
• NGSP, Factors That Interfere With HbA1c Test Results
• Limitations of Hemoglobin A1c in the Management of Type 2 Diabetes Mellitus