(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

HbA1c: Basic
understanding of the
diabetes yardstick.
Atikur Rahman 4 articles Follow
Certified Trainer | CLDP by WARD-UK

August 14, 2023

Open Immersive Reader

HbA1c is the gold standard for diagnosing and monitoring

patient response in treating diabetes mellitus. Let's have an
introductory discussion on HbA1c.

Hb-hemoglobin

Haemoglobin- proteins inside your RBCs (Erythrocytes),

carry oxygen for our cells. You have 250 million molecules
of haemoglobin packed in a single RBC.

Haemoglobin molecule inside your RBC

Messaging
HbA - What does the "A" stands for?

2 of 9 8/26/2023, 9:16 PM
(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

Actually, we have various types of haemoglobin molecules

like

• Haemoglobin A

• Hemoglobin A2

• Haemoglobin F etc.

Where the most common one with 97% prevalence is

haemoglobin-A in adults (maybe A stands for adult
haemoglobin)

Major types of Hb

HbA1c- why 1c?

When an HbA molecule is synthesized inside the RBC, it

tends to bind with various chemical species ('X') like
glucose, glucose-6-phosphate, fructose 1,6-di-phosphate,
etc. Then, these bound HbA molecules (HbA+X) are called
HbA1.

Formation of glycated haemoglobin (HbA1c) from the binding of glucose to

haemoglobin.

Now, let's see the chemical species ('X') which binds with
HbA.
Messaging
If X= fructose 1,6-diphosphate, then HbA is called HbA1a1

3 of 9 8/26/2023, 9:16 PM
(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

If X= fructose 1,6-diphosphate, then HbA is called HbA1a1

If X = glucose-6-phosphate, then HbA is called HbA1a2

If X = glucose, then HbA is called HbA1c

HbA0 = Pure haemoglobin A

And these three minors Hb (HbA1a1, HbA1a2 & HbA1c)

together are called HbA1. Why minor? Well, due to their
less prevalence; about 6% of total HbA is HbA1. Don't be
overwhelmed, the HbA1c is about 5% of total HbA for
healthy adult.

HbA1 = Includes HbA1a1, HbA1a2, HbA1c,

HbA1b etc.

HbA1c= Hemoglobin-A molecule chemically

attached with a glucose

If a blood sample of a healthy adult contains 1 million Hb molecules then, the

prevalence of HbA, HbA1 & HbA1c can be visualized as in the graph.

The HbA0, HbA1c, HbA1a1, HbA1a2 etc. hemoglobin types

were separated on cation exchange chromatograph. The
first fraction separated, probably the pure hemoglobin A,
was designated HbA0, and the following fractions were
designated HbA1a, HbA1b, and HbA1c, in their order of
elution. Being east-to-detect, HbA1c is of particular
interest. Moreover, HbA1c is the most abundant of these
fractions and in healthly subjects comprises
approximately 5% of the total HbA fraction.

Why HbA1c is high in DM?

Wait a minute! How are glucose molecules

getting access readily in RBC while the same
molecules are facing difficulties in entering Messaging

skeletal muscles & adipose tissues?

4 of 9 8/26/2023, 9:16 PM
(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

skeletal muscles & adipose tissues?

Well, glucose molecules are not dependent on insulin to

enter into RBCs. The RBCs have Glut-1 that are not insulin
dependent. While in skeletal muscles & adipose tissues,
there is Glut-4 which is insulin dependent for glucose
transportation.

The extent of glucose transport through Glut-1 in RBCs

solely depends on the plasma concentration of Glucose.

Since diabetic patients have persistently high

blood glucose, more glucose enters into the
RBCs through Glut-1. And so more HbA gets
glycated i.e., high HbA1c.

Why HbA1c is important?

• Diagnosis

Regarding diabetes, a worldwide guideline followed by

physicians is the American Diabetic Association, ADA
guideline. If you read this guideline, you will notice that
almost every advice about diabetes mellitus mentions
HbA1c. Following, you can have a glance on HbA1c ranges
for DM diagnosis.

HbA1c range in DM diagnosis | ADA guideline.

• Treatment- choice of hypoglycemic agents

When you get diagnosed as Type-II DM, initially your

doctor will start your treatment with metformin. As this
disease progresses, your doctor needs to add second
agents for your proper treatment. But the question is how
your doctor would know-

'When to add a second agent with Messaging

metformin?'

5 of 9 8/26/2023, 9:16 PM
(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

metformin?'

Here HbA1c will help you to find the answer. You have to
follow the goal HbA1c as mentioned in the ADA guideline.
For a non-pregnant adult, the goal HbA1c is below 7%.
That means, if you are taking hypoglycemic drugs and your
HbA1c is above 7%, then probably your treatment is not
going well.

Glycemic target (Goal HbA1c) for Diabetic patients by ADA guideline

Now, imagine you have tested your ever first

HbA1c and found it as 9%. Would your doctor
only prescribe metformin to treat your T2DM
(Type-II DM)?

The answer is 'no'. Because you are 2 points ahead of your

target HbA1c i.e., below 7% and the metformin can reduce
your HbA1c by 1.5 point maximum. So, you must be
prescribed with metformin + other hypoglycemic agents.

ADA says 'when A1c is >= 1.5 % (point) above the glycemic
target many patients will require dual combination
therapy to achieve their target A1c level' and

'Initial combination therapy should be considered in

patients presenting with A1c levels 1.5–2.0 % (points) above
target.'

Messaging

6 of 9 8/26/2023, 9:16 PM
(23) HbA1c: Basic understanding of the diabetes yardstick. | LinkedIn https://www.linkedin.com/pulse/hba1c-basic-understanding-diabetes-yar...

Logo | ADA

Again, imagine Mr. Rahman is a patient of

T2DM and his HbA1c is found 11%. Do we need
insulin to treat this T2DM patient?

The answer is 'YES'. According to ADA guidelines, 'it is

common practice to initiate insulin therapy for patients
who present with blood glucose levels A1C >10%.'

So don't hold the idea that only T1DM patients

need to take insulin.

• Monitoring- is the status quo going well?

If you are meeting glycemic goals with the help of your

current medications, ADA says you should assess your
HbA1c at least two times a year.

If your therapy (hypoglycemic agents or their dose) has

recently changed and/or you are not meeting glycemic
goals then, you should assess your HbA1c at least
quarterly.

Written by-

Md. Atikur Rahman

Certified trainer | CLDP by WARD-UK

References:

• Journal: doi: 10.4137/Bmi.S38440.

• ADA guidelines

Abbreviation:

• ADA =American Diabetes Association

• T2DM= Type-II Diabetes Mellitus

• DM = Diabetes Mellitus

• T1DM= Type-I Diabetes Mellitus

• Hb = Haemoglobin/Hemoglobin

• Glut-4 = Glucose Transporter- 4

• Glut-1 = Glucose Transporter- 1

Disclaimer: Information in this article has been simplified for

better understanding. Please be referred to ADA guideline for Messaging
detail treatment protocol of DM.

7 of 9 8/26/2023, 9:16 PM