Your A1c number has huge implications for your health. Your doctor uses A1c to diagnose you with diabetes or prediabetes, but the test can be inaccurate in many people, and there are plenty of doctors who are just not aware of it.
Hi, I'm Dr. Leonid Kim. I am board-certified in Internal Medicine and Obesity Medicine. In this article, I'll explain whether you're one of those people who cannot rely on their A1c, and, if you are, which other tests you need to get instead, including my favorite alternative to the A1c test. I'll also discuss the controversy surrounding the use of A1c in diagnosing prediabetes.
Why This Matters
The rates of diabetes are skyrocketing in the US and worldwide. According to the most recent estimates, 13% of US adults have diabetes, and a third of the US population meets the criteria for prediabetes. Because diabetes is the leading cause of kidney failure and new cases of blindness, the United States Preventive Services Task Force changed their recommendation last year to lower the age of screening for diabetes and prediabetes from 40 to 35 in those with overweight or obesity.
Personally, I think we as a healthcare field do not pay nearly enough attention to the devastating nature of insulin resistance in our bodies, which later manifests in many of the common conditions that plague us today, conditions like heart disease, strokes, fatty liver, dementia, and even many cancers. So it's extremely important to identify those at risk, and to do so, we have to use the correct diagnostic tools, which is why we need to talk about A1c.
A1c is a good test, but it has major limitations that are important for you to know. Let's get into it.
How A1c Works
A1c, or hemoglobin A1c, is a blood test that gives you an average of your blood sugar levels over the past few months. To understand how A1c can lead you astray, it's helpful to know how it works.
A1c is measured by looking at your hemoglobin, a protein inside your red blood cells that carries oxygen. The test measures the percentage of hemoglobin that is glycosylated, meaning it has glucose attached. The higher your sugar level is in your blood, the higher the percentage of hemoglobin that is coated in glucose, and that percentage of glycosylated hemoglobin is your A1c.
Your A1c percentage reflects the mean blood glucose over the entire lifespan of the red blood cell, which is usually about 120 days. However, it actually correlates best with the mean blood glucose over the previous 8 to 12 weeks. So even though we generalize and say A1c represents your average glucose over the past three months, more accurately, it reflects your sugars from two to three months ago. A1c is also relatively unaffected by recent fluctuations in glucose levels, so it wouldn't reflect changes that have happened over the past month.
How to Interpret A1c Percentages
So how do we interpret these percentages? An A1c of 6.5% or higher puts you in the diabetes range, and an A1c between 5.7% and 6.4% will put you in the prediabetes range. To put that in perspective, a diabetes threshold of 6.5% would mean your average glucose is around 140.
There is some controversy about the prediabetes range of A1c, or when one is considered to have prediabetes, which I'll go over later in this article.
What Can Cause a False A1c Result
Now that we know how we arrive at your A1c number, you can probably guess what factors can give you a false result. Anything that affects red blood cell turnover will have an impact on your A1c.
Conditions That Cause a Falsely High A1c
Conditions like iron deficiency anemia, or B12 and folate deficiency anemias, will give you a falsely high A1c, meaning you may be diagnosed with diabetes without actually meeting the criteria for it. These anemias are associated with decreased red cell turnover, which means hemoglobin is exposed to glucose for a longer period, resulting in higher A1c levels.
Other situations in which you'll see a falsely high A1c include splenectomy or absence of a normal spleen, chronic alcohol consumption, and chronic salicylate ingestion (usually from medications like aspirin).
There are also important racial and ethnic differences to consider when interpreting one's A1c. It's usually higher among African Americans, Hispanic Americans, and Asian Americans than among white Americans with similar plasma glucose concentrations, by about 0.3% to 0.4%.
Conditions That Cause a Falsely Low A1c
On the flip side, the conditions that usually underestimate your A1c, making it look better than it actually is, involve increased red cell turnover, which shortens hemoglobin's exposure to circulating glucose. These include conditions such as thalassemia, sickle cell anemia, and splenomegaly (enlarged spleen).
In addition, supplementation with vitamin E, especially at 600 milligrams per day or more, can also give you a falsely low A1c, because vitamin E interferes with glycation, or the binding of glucose to hemoglobin.
Of note, A1c is also not routinely used in pregnancy, as it's usually falsely low in the second trimester but may rise during the third trimester.
Conditions That Cause an Unreliable A1c (Either Direction)
On top of that, there are instances where your A1c can be either falsely low or falsely high, where you cannot have confidence in the results. These include advanced kidney disease, recent blood transfusions, and vitamin C supplementation.
What to Do If Your A1c May Be Inaccurate
So what do you do if you fall into one of these categories where your A1c may be falsely low or falsely high? You have several options.
Fasting glucose or oral glucose tolerance test.
If you're using the test to diagnose prediabetes or diabetes, one alternative is to measure fasting glucose or to have an oral glucose tolerance test, in which blood glucose is measured after a glucose challenge.
Serum fructosamine.
Another option is to use a test that measures your serum fructosamine, which reflects glycated albumin rather than glycated hemoglobin, as A1c does. Because the half-life of albumin is much shorter than that of a red blood cell (about 20 days for albumin versus 120 days for a red blood cell), fructosamine only gives you a snapshot of your average glucose levels over the past two to three weeks. This makes it a better assessment of recent changes in glycemic control. This test also has its limitations, particularly in conditions that affect albumin concentrations, such as severe liver disease or nephrotic kidney disease.
1,5-anhydroglucitol (GlycoMark).
Another option that's not commonly used is a test that measures 1,5-anhydroglucitol, commercially available as GlycoMark. This can offer a glimpse of your blood glucose levels over the past 1 to 2 weeks.
Continuous glucose monitor (CGM).
My favorite alternative to A1c is using a CGM, or continuous glucose monitor. The data from a CGM is real-time and provides information on important metrics such as time in range (the amount of time spent in the target blood sugar range), time in hypoglycemia (dangerous periods when blood sugar levels are too low), and blood glucose variability. Unlike A1c, which gives an average of sugar levels, CGMs can also provide data on high peak glucose levels, which are associated with an increased risk of cardiovascular disease and Alzheimer's.
The downside of using a CGM is its cost, as it can get quite expensive if not covered by insurance. CGMs are currently indicated for all patients with type 1 diabetes. In patients with type 2 diabetes, intermittent CGM use is indicated for those on intensive insulin therapy, patients with hypoglycemia, or when significant therapeutic changes are made, like initiating or increasing insulin. In fact, there's growing evidence showing the benefit of using CGMs with type 2 diabetes, independent of the treatment regimen.
A1c Is Still the Gold Standard, But Know Its Limits
Having settled that, A1c remains the gold standard for modern glycemic control in patients with diabetes. It's the most widely used clinical test for diagnosing diabetes and monitoring treatment efficacy. In fact, the FDA uses A1c as the primary endpoint to demonstrate glycemic lowering in new diabetes drugs.
But it's just as important to know when your A1c is misleading, as it involves making important decisions regarding your health, decisions like whether you have prediabetes or diabetes, or what medications you need to be on.
The Controversy Over A1c Cutoffs for Prediabetes
Lastly, it's crucial to discuss the controversy surrounding A1c cutoffs used to diagnose prediabetes, as guidelines vary by location.
The CDC and the American Diabetes Association consider someone to have prediabetes once their A1c reaches 5.7%. However, the WHO does not endorse using A1c to diagnose prediabetes. Instead, they recommend using a fasting glucose test or a two-hour oral glucose tolerance test.
Both Canada and the UK, like the US, also recommend using A1c to diagnose prediabetes. However, instead of using a 5.7% cutoff as we do in the US, they recommend using an A1c of 6%.
Who's to say who's right, or which country has the better approach? I personally favor the more aggressive approach of screening for and treating prediabetes at earlier signs of insulin resistance, like they do in the US.
However, I question the use of A1c to accomplish that goal. In some ways, A1c is often inaccurate in measuring the true level of insulin resistance, for the reasons we discussed in this article. In other words, A1c doesn't capture enough people at risk, as it misses important metrics like glucose variability or post-meal glucose levels, metrics that can signal insulin resistance even with a normal A1c.
Conclusion
A1c remains one of the most useful and widely used tools we have for diagnosing and managing diabetes, but it is not infallible. Conditions affecting red blood cell turnover, certain medications, supplements, pregnancy, kidney disease, and even race and ethnicity can all skew your results in either direction. If you have a condition that could be affecting the accuracy of your A1c, or if your A1c doesn't seem to match how you feel or your other health markers, it's worth talking to your doctor about alternative tests like fasting glucose, oral glucose tolerance testing, serum fructosamine, or a continuous glucose monitor. Understanding the strengths and limitations of A1c empowers you to make better, more informed decisions about your health.
FAQ
What is A1c, and what does it measure?
A1c, or hemoglobin A1c, is a blood test that measures the percentage of hemoglobin in your red blood cells that is coated with glucose. It reflects your average blood sugar levels, most accurately over the previous 8 to 12 weeks.
What A1c level indicates diabetes or prediabetes?
In the US, an A1c of 6.5% or higher is considered diabetes, and an A1c between 5.7% and 6.4% is considered prediabetes. Other countries, such as Canada and the UK, use a prediabetes cutoff of 6% instead.
Can A1c results be wrong?
Yes. Conditions like iron, B12, or folate deficiency anemia, absence of the spleen, chronic alcohol use, and certain medications can falsely elevate A1c. Conditions like thalassemia, sickle cell anemia, splenomegaly, and high-dose vitamin E supplementation can falsely lower it. Some conditions, like advanced kidney disease, recent blood transfusions, and vitamin C supplementation, can make results unreliable in either direction.
What tests can be used instead of A1c?
Alternatives include fasting glucose testing, oral glucose tolerance testing, serum fructosamine (reflecting the past two to three weeks), 1,5-anhydroglucitol (GlycoMark), and continuous glucose monitoring (CGM), which provides real-time data on glucose patterns, variability, and time in range.
Why does the author prefer a continuous glucose monitor (CGM)?
A CGM provides real-time, detailed data, including time in target range, time in hypoglycemia, and glucose variability, information that A1c alone cannot capture. It can also reveal high glucose spikes linked to cardiovascular disease and Alzheimer's risk, though cost can be a limiting factor.