What is HbA1c and What are its Limitations?

red blood cells

The HbA1c test is a common one in almost every diabetics life. It comes highly recommended from seemingly everyone and is often touted as the “gold standard” by the well read health conscious neighbor next door. This reputation is well earned and supported by a large body of research that often concludes with its importance to glucose monitoring.

In this article we will outline the key concepts and summarize latest research to understand the limitations of the test.

What is HbA1c

Red blood cells (RBCs) circulating around the body contain a protein called Haemoglobin (Hb or Hgb) that transports oxygen from the lungs to all the cells of the body. As you can probably tell, this is what makes your blood red.

There are many types of Haemoglobin, but at about 6 months of age, most of the Haemoglobin in the body would be “type A” which stands for Adult (HbA). This type consists of type A1, type A2 and others, with type A1 representing ~95-98% of HbA. Type A1 also has the sub-types A1a, A1b, A1c, and other, where A1c is the result of the interaction with glucose.

As red blood cells packed with haemoglobin circulate your body, they often bump into glucose molecules that are present in your blood stream and sometimes react to produce glycosylated haemoglobin (A1c). The more glucose that is present in the blood stream, the higher the opportunities for interaction with the haemoglobin inside the red blood cells. Additionally, the longer your blood cells live the more they can bind to haemoglobin.

Putting all that together, we see that HbA1C (or A1c for short) is actually “Haemoglobin of type A1 that is has reacted with glucose (glycosylated)“. When we perform the HbA1c test we are measuring what percent of the haemoglobin is glycosylated.

An important note to keep in mind is that the HbA1 is not structurally different from HbA1c, the only difference is that the latter has glucose molecules binding to it.

What does the HbA1c test tell us?

The test tells us what percent of the Hb in your red blood cells has bound to glucose from your blood stream over the cell’s life span, usually between 90 and 120 days.

Because of the long life of RBCs, the test can give patients and physicians a great average blood sugar reading over the past 3 months or so. Patients with prick tests will appreciate the convenience of this as opposed to finger pricks every few minutes for 3 months to get the same result.

Test results between 4% and 6% are considered normal while 7% to 8% is considered high and 6.5% as the threshold for a diabetes diagnosis.

At this point, it is clear that there is a strong relationship between Red Blood Cells, Haemoglobin and Glucose.

What are the limitations of the HbA1C test?

Since this test works by investigating the Hb protein within the RBCs, anything that affects any of these can result in inaccurate readings. There are many common things that fit into this category.

Generally speaking, these factors could either produce a false increase or a false decrease in the measured glycosylated haemoglbin measured. False Increase

Any condition/factor that can increase the lifespan of RBCs can also result in higher test results. This is because the longer the cells have to interact with circulating glucose, the more opportunities for glucose to bind to them. When testing an individual with long living RBCs it is more likely to be looking at older cells with more glucose attached to it.

These include:

  1. Iron deficiency anaemia (30% of the population is anaemic)
  2. Vitamin B12 and Folic Acid deficiency anaemia
  3. Hyperbilirubinaemia - High bilirubin levels in the blood, presents as yellowing of eyes and skin.
  4. Alcohol intake
  5. Some drugs - Salicylates and opioids.

False Decrease

Unlike the false increase, a false decrease happens when the lifespan of RBCs is shortened resulting in younger cells circulating with less time to interact with circulating glucose.

These include:

  1. Pregnancy
  2. Splenomegaly - An enlarged spleen
  3. Some drugs and supplements - Inteferon A, cephalosporin, levflaxin penicillin, anti-inflamatories, vitamin E, etc
  4. Homozygous Haemoglobinopathy - A genetic blood disorder
  5. Renal disease

Other Factors

  1. Age - for every 10 years of age, there is an associated 0.1% increase in HbA1c
  2. Race - Caucasians have a 0.1% - 0.4% decrease in HbA1c when compared with non-Caucasians with the same glucose levels.

The HbA1c test, otherwise known as glycosylated haemoglobin, provides crucial insight into the average body glucose levels and helps diabetes care teams monitor patient progression. The limitations outlined in this article highlight some of the pitfalls of the test and aim to provide context to the results obtained from the test.

As always, be clear and honest with your care team about the medications you are taking and any conditions you may have to provide them with the necessary context to guide their recommendations.

This article draws from a lot of the latest research in diabetes and haematology, key resources were: Cleveland Clinic, Diabetes Self Management, Georgia et al., and Rene Rodriguez-Gutierrez and Victor M. Montori