Sharon Orrange, MD, MPH
Dr. Orrange is an Associate Professor of Clinical Medicine in the Division of Geriatric, Hospitalist and General Internal Medicine at the Keck School of Medicine of USC.
Posted on July 2, 2020

The preferred way to screen for diabetes is with an A1C test. It’s easily done with a fingerstick in your doctor’s office and doesn’t require you to fast (not eat) prior to the test. In ideal situations, if your results from two consecutive tests are both 6.5% or higher, then your doctor can confirm that you have diabetes. But circumstances are often less than ideal. We’ll talk about times when your A1C test could be inaccurate below.

What is hemoglobin A1C?
Hemoglobin is a protein that sits inside red blood cells and is responsible for carrying oxygen throughout your body. Interestingly, hemoglobin can also attach to glucose (or sugar) traveling in your blood, and that hemoglobin-glucose combination is known as glycosylated hemoglobin, hemoglobin A1C, or HbA1C. The higher your blood sugar levels are, the higher your hemoglobin A1C levels will be.

What does an A1C test measure?
An A1C test measures the percentage of hemoglobin in your blood that carries glucose. The higher the amount of glucose in the blood, the higher the A1C percentage. A normal A1C measurement is less than 5.7%, while an A1C of 5.7% to 6.4% could suggest prediabetes, and an A1C of 6.5% or higher usually means diabetes.

The great thing about an A1C test is that it represents your average blood sugar levels over 2 to 3 months. In other words, it isn’t affected by the pizza you had the night before, and you don’t have to fast for the test to be accurate. That’s because glucose stays attached to hemoglobin for as long as the red blood cell that holds them remains in your bloodstream (which is about 2 to 3 months).

Certain health conditions that affect your blood and hemoglobin can cause your HbA1C test to be inaccurate.

When your A1C test says you have diabetes, but you really don’t
The following conditions can falsely raise your A1C test results, making you think you have lots of glucose in your bloodstream when you don’t.

• Certain types of untreated anemias: Anemia caused by a lack of iron, vitamin B12, or folate (vitamin B9) can falsely raise your A1C test results. Your body needs these vitamins and minerals to create new, healthy, red blood cells and replace older, dying ones. If your body isn’t making new blood cells, that means you’ll have more of the older cells floating around, including ones that have already picked up glucose.
• Kidney failure or chronic kidney disease: Abnormal kidney functioning is a problem that can happen in people with diabetes. Chronic kidney disease can lead to low vitamin and mineral levels and anemia, which, as you saw above, can cause your A1C test results to be falsely high.
• Extremely high triglycerides: Triglycerides are a type of fat found in your blood. When you have too much of this fat (where your triglyceride blood test is over 1,750 mg/dL), it can make your A1C levels seem higher on your test than they really are.

When your A1C test says you don’t have diabetes, but you really do

The following conditions can falsely lower your A1C test results, making you think you don’t have excess glucose in your bloodstream when you do.

• During treatment of certain anemias: We talked about some anemias above. If you’re taking iron or vitamin B12 supplements to treat those anemias, you’re encouraging your body to make new red blood cells. This can cause your A1C test to be falsely low. (Again, if you have an iron deficiency anemia and you’re NOT treating it, your A1C test will be falsely high.)
• After donating blood: Your A1C test results will be inaccurately low after a blood donation (or in other situations of major blood loss). When your body is in a low-blood state, it will start to make red blood cells more quickly, and you’ll have newer red blood cells overall. That means the percentage of hemoglobin A1C in your bloodstream will be lower, too.
• During pregnancy: A1C can be falsely low during pregnancy because the body is in overdrive making more (younger) red blood cells to deliver oxygen to the growing baby. Even so, A1C is still used to monitor pregnant women with diabetes. The target A1C in pregnancy is below 6%.
• Hemolysis: Hemolysis is when your red blood cells are destroyed, cutting short their lifespan. It can happen as a result of autoimmune diseases, taking certain medications (like ribavirin or interferon alpha), or genetic blood disorders like hereditary spherocytosis.
• During erythropoietin treatment: Erythropoietin, the active ingredient in Epogen and Procrit, is used to increase red blood cell production after chemotherapy or if you have profound anemia caused by extremely low iron levels. The influx of new red blood cells can cause a falsely low A1C test.
• Hemodialysis: Both hemodialysis and peritoneal dialysis may falsely lower A1C levels. If you have kidney failure on dialysis, A1C levels may not be the best way to monitor your diabetes.

Blood donations can make your A1C test inaccurate either way
If you’ve just received donated blood in a blood transfusion, your A1C test results will be unreliable. A transfusion can affect your measurement in many ways, as it dilutes your red blood cells with someone else’s red blood cells.

Race and ethnicity can affect A1C
The A1C test works best on hemoglobin A, the most common type of hemoglobin that people have. But depending on where in the world you (or your ancestors) come from, your blood might have a different type of hemoglobin. These are called hemoglobin variants, and they are more common if you or your family come from Africa, South and Southeast Asia, or the Mediterranean.

Having a hemoglobin variant such as hemoglobin S, C, D, or E, can affect the accuracy of an A1C result. Luckily, many labs now run A1C tests that are not affected by hemoglobin variants. There is a full list here. If you have a hemoglobin variant, you and your provider can work together to find a lab that will give you accurate A1C results.

Is there an alternative to the A1C test?
If you can’t rely on an A1C test, the next best test to measure blood sugar control is the fructosamine blood test. Diabetes specialists will check the concentration of a protein called fructosamine in your blood to get a relatively long-term estimate of your blood sugar levels.