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What is Hemoglobin A1C

2/18/2022

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​When it comes to diabetes There are two standard tests (well, there are some others) to determine if someone is Diabetic. They are blood glucose and Hemoglobin A1C test, also called HbA1c, glycated hemoglobin test, glycohemoglobin, glycosylated hemoglobin, or shortened to A1C, HbA1c. 
A hemoglobin A1C test measures the amount of glucose (sugar) attached to hemoglobin. Let’s talk about what hemoglobin is so that we can better understand the hemoglobin A1C test and what is measuring. 
Picture
Hemoglobin Illustration from Anatomy & Physiology Connexions Web site https://openstax.org/books/anatomy-and-physiology/pages/1-introduction

What is Hemoglobin

Hemoglobin (or haemoglobin) is the iron containing protein in the red blood cells known as erythrocytes. It is responsible for transporting oxygen to our tissues, then transporting the spent oxygen called oxyhemoglobin from our tissues to the lungs to be expelled.

How is hemoglobin made

Hemoglobin’s journey begins in the bone marrow.[1]  This process known as hematopoiesis, happens in the spongy tissue inside the bone. Inside this environment, stem cells are formed. These stem cells develop into different cells, however, we will stick to the 3 types of blood cells: red, white and platelets. 
Stem cells are like rabbits.  Rabbits reproduce quite fast and efficiently. Same with our cells. Stem cells, make copies of themselves constantly. In fact, as you are reading this, you have more than likely created thousands of new red blood cells.
​In the case of red blood cells, once the copy is mature enough to be functional, they travel out of the bone marrow and enter the blood stream. If you want to go really in depth, watch the video above, it is quite fascinating. 
For our purposes, let’s just stick with what happens after a stem cell creates a red blood cell. When the hematopoietic stem cell creates a myeloid stem cell, it matures from a proerythroblast into a reticulocyte and then an erythrocyte. 
When you get your blood drawn for a yearly checkup, if you have a proper CBC, chem screen and comprehensive metabolic profile it will include reticulocyte values. This can tell us how well your bone marrow is creating blood cells. Erythocytes are your red blood cells. Red blood cells are made up of different components but do not contain a nucleus or organelles like other cells in our body. 
Did you know Erythrocytes are the most abundant cell type in the blood? Red blood cells carry oxygen to all parts of the body and also takes the carbon dioxide to the lungs to be expelled with our exhalation. 
Red blood cells have a biconcave shape, meaning, both sides curve inwards. Think of pizza, the crust curves inward with a slight depression slowing towards the middle. The flexible sphere-shape of the red blood cell is designed for ease of maneuvering through the blood through arteries and teeny-tiny veins. 
Picture
Stem cells maturing into one of three types of mature blood cells: red blood cells, platelets, and white blood cells. Precursor cells are also shown: stem cells, myeloid blasts, lymphoid stem cells, and lymphoid blasts. | Alan Hoofring (Illustrator)
The biconcave shape also helps increase the surface area to allow for oxygen and carbon dioxide to easily diffuse onto the membrane of the red blood cell. What keeps the oxygen and dioxide in place is the help of hundreds of millions of hemoglobin proteins which binds it to the sphere. Hemoglobin is what gives blood its red color. 
What triggers us to need more red blood cells is our kidneys. If the kidneys detect low oxygen levels, they will produce and release the hormone erythropoietin to stimulate production of red bone marrow; those stems cells we talked about. 
Think about when you are running, you need more oxygen for your muscles, tissue and your lungs. We do not have to think about it, our body just gets busy creating red blood cells with millions of hemoglobin attaching oxygen to help our muscles work and to help us breathe and dumping the spent oxygen so we can breathe it out. This is basically the function of red blood cells, oxygen and carbon dioxide, energy in, energy out. All 25 trillion red blood cells continuously do this for their life span of about 90-120 (3-4 months).
Our spleen, liver and lymphatic system are always checking on the health of these red blood cells, removing them from circulation when needed sending them to the white blood cells that then engulf and digest them. It is amazing that we have our own recycling and waste disposal system happening right in our cells. The lymphatic system is part of the highway in keeping our system clean and sludge free. It dumps everything into the bowel for removal.​
 Now that we understand hemoglobin are proteins that bind oxygen and dioxide to the red blood cells for transpiration, now we can get back to understanding what is hemoglobin A1C and why it is measured especially in the case of diabetes.

What happens when we eat carbohydrates

When we eat carbohydrates and fats, our body breaks it down into glucose. Our mouth enzymes start the process, but the biggest breakdown happens in the small intestine with the help of enzymes released by the pancreas. As the sugars and fats are broken down into simple glucose molecules, this also triggers the pancreas to release the hormones insulin and glucagon to help monitor the amount of glucose entering the blood stream. It monitors when to store glucose if we eat too much or release the glucose back into the blood stream for energy. When we are eating foods, insulin increases hormones for;​
Glycolysis; involves converting glucose to pyruvate for energy use (in the metabolic pathway for ATP and NADH)[2]
Glycogenesis; the formation of glycogen from glucose stored in the liver and muscles.[3]
Lipogenesis; converting glucose or other substrates into fatty acid and triglycerides for storage in the liver (sometimes fat cells)[4]​
These three metabolic reactions decrease glucose in the blood stream by converting it for storage in the liver mainly, and sometimes fat cells. 
If we have not eaten in while, glucagon is released causing the liver to release stored glucose (glycogen) into the bloodstream (glycogenolysis), thereby increasing the level of glucose in the bloodstream[5] so we can get some energy.
Most of us eat carbohydrates, we tend to break them down into simple glucose molecules to create the energy we need to run our body and brain. It is the main fuel source of the body. 

What is Hemoglobin A1C

When glucose enters our blood stream from our gut, it attaches to hemoglobin, a normal physiological feat. This glucose is called glycosylated hemoglobin, or glycohemoglobin, hemoglobin A1c (HbA1c).[6]
Hemoglobin A1c compound is produced when glucose reacts with the amino group on a hemoglobin molecule forming a ketoamine. The glucose molecule is attached to one or both N-terminal valines of the β-polypeptide chains of hemoglobin. The HbA1C formation is proportional to the blood glucose concentrations.[7]
Depending on the amount or lack of glucose attachment, we can look at the Hemoglobin A1c formation on red blood cells over the lifespan of the blood cell (90-120 days) to determine if there is too much or too little glucose in the blood stream.​​

What is the hemoglobin A1C test purpose

This is where we look to the serum hemoglobin A1c (HbA1c) test to measure the amount of glucose attaching to the hemoglobin. Since red blood cells live on average 90-120 days, the hemoglobin A1C (HbA1c) test [18] is looking at what has been happening over the last 90’s days and gives an average.[9]​
If the hemoglobin A1c (HbA1c) lab test comes back with high values this indicates what has been happening over the last 3 months. Your body has been busy trying to figure out what to do with the excess amount of glucose. If you recently changed your diet, and your hemoglobin A1c (HbA1c) lab test comes back with high values, remember, it is showing from three months ago, not the present moment.
If you are wanting to know the impact of your diet on your hemoglobin A1C, you would have to continue for 4 months. Then, have another serum hemoglobin A1C test done and see how your diet has impacted your A1C lab results.

What is a good hemoglobin A1C normal range

Each lab has their own hemoglobin A1C ranges. There is also what I call, conventional hemoglobin A1C levels, which is used to determine whether a person requires medication. This is the actual purpose of the hemoglobin A1C test. Collectively, conventional
  • Hemoglobin A1C (HbA1c) normal range is between 4.0 -5.6 % This means, there is no concern for diabetes.
  • A high hemoglobin A1C (HbA1c) of 5.7-6.4% indicates prediabetes meaning at a greater increase of developing diabetes
  • A high hemoglobin A1c l(HbA1c) evel greater than 6.5% is a diagnosis of diabetes
Picture

Functional Hemoglobin A1C levels

There are also functional levels of hemoglobin A1C which is not rooted in the determination of medication, rather, where the physiology needs to be supported through diet and lifestyle upgrades. Functional levels are similar and include;
  • A normal or optimal functional level of hemoglobin A1C is 4.0-5.7%
  • An increased hemoglobin (HbA1c) above the optimal range 5.7% is a sign of not controlling long term glucose levels very well.
  • A hemoglobin A1C (HbA1c) greater than 6.4% is a diagnostic for Diabetes.
An increased hemoglobin (HbA1c) above the optimal range 5.7-6.5% they are possibly in the insulin resistance phase, also known as pre-diabetic state. This is known as hypoglycemia. This is often due to hyperinsulinemia, insulin sensitivity or insulin resistance which if not corrected may eventually lead to type II diabetes. It is not a fast rule. A good functional practitioner will look at other factors in the person’s lifestyle and diet that may be contributing to the high hemoglobin A1C lab value. We can also look at other lab markers to determine the course of action such as
  • Fasting blood glucose
  • Blood glucose 3.5-4 hours after a meal
  • Estimated average glucose (eAG)
  • C-peptide
  • Fructosmine
  • GlycoMark
  • Adiponectin
  • GGT
  • CRP
  • ALT/AST ratio
  • Uric acid
  • Insulin
  • Homocysteine
  • Anion Gap
  • Organic acids
  • Stool test elastase-1, Calprotectin
  • Hormones
  • Oral glucose tolerance with or without insulin levels

Can you have a low hemoglobin A1C

There is such a thing as low hemoglobin A1C. A low hemoglobin A1C (HBA1c) test is between 4.2-5.6%. This would be considered low to low-normal hemoglobin A1C. Less than 4.1% may be caused by an inability to maintain adequate long-term levels of glucose or may have something to do with diet.

What causes a low hemoglobin A1c

We must also look at other conditions such a dysfunction of the spleen, or splenectomy, iron deficiency anemia, pancreatic function, low blood pressure, adrenal insufficiency, alcohol, lead toxicity and other conditions. We also need to look at other functions that may shorten the lifespan of red blood cells which would influence hemoglobin A1C lab values such as the various types of anemia including hemolytic anemia, chronic blood loss, sickle cell anemia disease, chronic renal issues, pregnancy
Picture
U.S. Naval Hospital Guam's phlebotomist Dio Patague draws blood from the arm of Hospital Corpsman 1st Class Karla Manuel during the opening of the new blood donor center at the hospital's laboratory. | U.S. Navy photo by Mass Communication Specialist 2nd Class Gabrielle Blake

How do I prepare for a hemoglobin A1c test

Typically, when we have regular routine blood tests done, we fast for it. Do we need to fast for a hemoglobin A1C test? No. The reason, it is testing the amount of glucose that has attached to the hemoglobin over the last 90-120 days. Therefore, it is not affected by you eating and drinking before the test. If you are having just a hemoglobin A1C test, show up to the lab appointment on time. The phlebotomist will inset a needle into the vein in your arm to take a sample of your blood. That it is.

Should I be concerned if my Hemoglobin A1C is high

If your hemoglobin A1C levels are high depends on how high. But, to answer the question, yes, you should be concerned. An increased hemoglobin (HbA1c) above the optimal range 5.7% is a sign of not controlling long term glucose levels very well. This is what is referred to as insulin resistance or pre-diabetes. This is a wakeup call. It’s a warning that you need to change something in your diet and lifestyle. If you have read this far and are concerned, I can help you with this. Studies have shown a shift in diet can help shift your hemoglobin A1C scores back into the optimal range.
We know that a high A1C is a concern for diabetes, and is often monitored in those with diabetes, but what if you are not diabetic? Or, what if you are diabetic and A1C is high, is it just for monitoring glucose in the blood? ​We now know that hemoglobin is what glucose sticks to. If the production of hemoglobin changes, then ratio of hemoglobin to glucose A1c will also alter. 

Hemoglobin A1C and anemia 

When there is an iron deficiency, the percentage of glycosylated hemoglobin goes up. Iron-deficiency anemia may raise a person's A1C as much as 1.6 percent, [10] but, it will not affect blood glucose. Whether diabetic or not, if there is an iron deficiency, it needs to be treated and may just bring hemoglobin A1C under control ​When testing for iron deficiency, it is important to ask for the following to be on the lab requisition form
  • Red blood cell (RBC) count, which are the cells that carry oxygen
  • White blood cell (WBC) count, which are the cells that fight infection
  • Hemoglobin, the proteins in blood cells that carry oxygen
  • Hematocrit, the percentage of red blood cells compared to the total blood
  • Platelets, which are compounds that help with blood clotting
  • Mean corpuscular volume (MCV), which measures the average size of the red blood cells
  • Ferritin is an iron-containing protein in the blood. measures the amount of ferritin in the blood, also is used for inflammation, but is also a true measure of used iron
  • Total iron binding capacity (TIBC) checks for levels of iron in the blood
  • Transferrin saturation is a protein that binds to iron to get it into the cells
These markers are crucial to understand where and what type of anemia you may be dealing with. These markers suggest an iron deficiency anemia. If these markers come back normal, then you would look to a possible B vitamin or other nutrient type anemia
This is where we are looking at B vitamins, folate, copper, chromium, vitamin C as these all play a role in the production of hemoglobin. In this case there could be a hemoglobin type anemia known as microcytic or macrocytic anemia. Before getting your blood drawn add the following to your lab requisition form 
  • Homocysteine: used for cardiovascular events, but also measures vitamin B6, B12 and folate.
  • Serum folate, measures the amount folate
  • Serum B12, measures circulating B12 but is not very accurate.
  • Urinary methylmalonic acid (MMA), is a better way to test for B12 cobalamin deficiency. MMA is the protein made to work with cobalamin
I have highlighted the tests in red, that are normally missed on a routine lab requisition form. You will have to ensure these are added in order understand where and what type of anemia. 
It is important to know your hemoglobin A1C, but it is also important to understand why it is out of the reference range so that you can do what can to bring it under control and not be misdiagnosed. 
A hemoglobin HgA1C above 5.2% is associated with an increase in your brain shrinking. Think dementia and alzheimers (which is considered type III diabetes). MRIs have shown in diabetes where the brain is not getting fed enough glucose, end up with brain tissue rigidity, and less energy flow. 
If we do not have adequate vitamin B12 and iron this is going to slow down the development of red blood cells and we will see an impact on the hemoglobin A1C lab values. Studies have confirmed that an HbA1c greater than 5.5% increases the risk of retinopathy and an HbA1c greater than 6.0% increases the risk of chronic kidney disease.
Other factors affecting hemoglobin A1C scores that may be overlooked include;
  • Extremely high triglyceride levels, typically over 1750[11]
  • Elevated bilirubin levels as little as 21 mg/dl. 
  • Kidney dysfunction (uremia)
  • Alcoholism and alcohol abuse[12]
  • Lead poisoning[13]
  • Opioid use (painkillers)[14] street drugs
  • COVID 19 [15]
Get your own on demand video access to Long Covid and what to do about it

​COVID 19 and increased hemoglobin A1C

We must look at the impact of COVID-19 on hemoglobin A1C. A systematic review and meta-analysis [16] looked at studies from December 1, 2019 to May 15, 2020  investigating blood glucose or glycated hemoglobin A1c (HbA1c). Three studies reported blood glucose and HbA1c according to the severity of COVID-19 and were included in this meta-analysis. The combined results showed that severe COVID-19 was associated with higher blood glucose. In addition, HbA1c was slightly higher in patients with severe COVID-19 than those with mild COVID-19, yet this difference did not reach significance. 
What we need to understand and remember, hemoglobin A1C is an accumulation of the last 90 days, 3 months. If you have blood work done and also contracted SARS CoV2 this may be a reason why your Hemoglobin A1C has increased. 
We also know that COVID-19 also affects iron and hemoglobin thus, will impact hemoglobin A1C lab values. You can check out my article on Long Covid and symptoms. Or, if you would like to get the whole scoop on Long Covid you can own your own on demand Long Covid series, check it out here.
It is still too early to know how the long term effects of vaccination will affect our health including hemoglobin A1c. We must take this into effect when looking at hemoglobin A1C values. Make a point to record the dates of COVID 19 vaccinations including booster shots. If they have taken place in the last 3 months, may influence lab values. However, with this said, Long Covid and vaccination long term effects are still being researched. In other words, we are the cohort for understanding how this experimental vaccine is affecting the future of our health.[17]

Should I worry about hemoglobin A1C high values?

A hemoglobin A1C (HbA1c) greater than 6.4% is a diagnostic for Diabetes. Is this the end? No! There are numerous strategies to help turn this around. Studies have shown a shift in diet and lifestyle can positively impact lab values and better support  how glucose is used in the body so that it does not oversaturate red blood cells.
Should you worry? Yes and no. No, because worry doesn’t change anything. Yes, because worry should prompt you to be proactive and do something about it now. It is not over, it is time to get to the root cause of your hemoglobin A1C high score. 
There are other blood lab values we can look at that can help determine where to start to know how to nutritionally support you for a better hemoglobin A1c test outcome. If you would like help in getting your hemoglobin A1c score into an optimal range, reach out. Email me HelloKarenLangston@gmail.com or call me (347) POO-WELL (347 766. 9355) and let’s get you feeling great again! 
References
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