Sickle Cell Trait + Diabetes: Why Your A1C May Not Be Accurate

For most people, your A1C is a three-month average. Higher numbers mean more sugar in your blood, which over time may raise your risk of complications from diabetes. Most healthcare providers look at A1C levels in a range to determine diabetes risk and assess if treatment plans are working. But what if that number is wrong? For millions of people with sickle cell trait (SCT), it might be.

 When sugar enters your blood, it sticks to a protein in your red blood cells. This creates something called “glycated hemoglobin.” The more sugar in your blood, the higher your A1C number. In short, that’s the calculation that the A1C test counts on. 

But in truth, the math only works if your hemoglobin behaves the way the test expects. If you have health factors that could alter the context of your results, like a hemoglobin variant caused by the sickle cell trait, it might not.

What is sickle cell trait and why does it matter?

SCT is a genetic hemoglobin variant. SCT means you carry one copy of the gene that causes sickle cell disease. People with sickle cell disease have two copies of this gene. Between one and three million Americans have SCT, including 8 to 10% of Black Americans. Many people with SCT have no symptoms and don’t even know that they have it, especially if they were born before newborn screening became routine.

A landmark study published in JAMA found that SCT is associated with lower A1C readings compared to what blood sugar levels actually are. The likely reason: the hemoglobin variant may shorten the lifespan of red blood cells, which means glucose has less time to accumulate—producing a falsely low A1C. The researchers recommended that clinicians following Black people whose A1C falls within 0.3 percentage points of a diagnostic cutoff should also use additional blood glucose measures.

What does an incorrect A1C actually mean for you?

If your A1C reads falsely low, your healthcare team might think your blood sugar is better controlled than it actually is. That can mean delayed diagnoses, undertreated diabetes and a mistaken sense of safety. You could be walking around with blood sugar high enough to cause complications while your lab results say you’re fine.

It also feeds into the health equity issues already present in diabetes care. Black Americans are twice as likely as white Americans to die of diabetes and three times as likely to be hospitalized for diabetes-related complications. If the primary tool used to monitor their care is systematically underreporting their blood sugar, that gap gets wider—and nobody sees it coming.

On the flip side, some hemoglobin variants can cause falsely high A1C readings. That means a person could be overtreated—given medications or insulin doses based on numbers that overstate the problem. Either direction is dangerous. And the person living with diabetes is the last one to know, because the number they’re being judged by doesn’t reflect what’s actually happening in their body.

And SCT isn’t the only variant that can interfere. Hemoglobin C trait, hemoglobin E trait and elevated fetal hemoglobin can all affect A1C accuracy. Black, Latinx and Asian Americans report the highest rates of hemoglobin variants overall, meaning the people most likely to have diabetes are also the most likely to get an inaccurate reading from the test used to manage it.

Are there alternative tests?

Yes. Fructosamine and glycated albumin are blood tests that measure glycated proteins instead of glycated hemoglobin. They reflect average blood sugar over the past two to three weeks rather than two to three months. More importantly, they’re not affected by hemoglobin variants or red blood cell lifespan. These tests aren’t used as widely as A1C, but they’re clinically validated alternatives. If your A1C might be unreliable, your healthcare provider can order one of these tests to get a more accurate picture.

Continuous glucose monitor (CGM) data can also provide a clearer picture of your actual glucose patterns than a single A1C number. If you wear a CGM, your glucose management indicator (GMI), an estimated A1C calculated from your sensor data, may actually be more accurate than the lab test.

But remember: Your A1C is only useful if it’s accurate. And for too many people, disproportionately people of color,  it isn’t. The good news? Better tools exist. The bad news is that often, you might not be offered them unless you ask.

What to watch for

You don’t need a lab test to start noticing the signs. A few simple comparisons between your daily numbers and your lab results can tell you whether it’s time to ask more questions.

• The National Glycohemoglobin Standardization Program maintains a chart showing which A1C assays are affected by which variants. 
• If your A1C and your day-to-day blood sugar numbers don’t match up that’s a red flag.
• If you’re on a CGM, compare your GMI to your lab A1C regularly. If there’s a consistent gap of 0.3% or more, bring it to your care team’s attention and ask whether a hemoglobin variant could be the reason.

How to talk about it with your healthcare team

Advocating for yourself doesn’t require medical expertise—just the right questions. Here’s where to start.

• Ask your healthcare provider: “Do you know if I carry a hemoglobin variant that could affect my A1C?” If you’re Black, of African descent or part of another population with higher rates of hemoglobin variants, this is a question worth asking. 
• Ask whether a fructosamine or glycated albumin test would be appropriate for you. 
• Ask your lab which method they use to measure A1C as some methods are more affected by hemoglobin variants than others. You can refer to the National Glycohemoglobin Standardization Program chart for more on each method.
  

The bottom line

A1C is a useful tool, but it’s not 100% accurate, especially if you carry a hemoglobin variant that most people never get tested for. Trust your CGM data, trust what your body tells you and don’t be afraid to ask your care team for another way to measure your blood sugar. You know yourself better than any single lab result does.

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