The document discusses the significance of glycated hemoglobin (HbA1c) as a clinical marker for diabetes management, detailing its discovery and development as a test to assess average blood glucose levels over a two to three-month period. It highlights the correlation between HbA1c levels and diabetes control, illustrating the test's importance in diagnosing diabetes and guiding treatment decisions. Additionally, the document provides insights into how HbA1c testing has evolved and its role in monitoring long-term glucose levels for individuals with diabetes.

1. Glycated Hemoglobin (HbA1C)
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The Discovery
The hemoglobin protein is a long chain of amino acids that folds upon itself to form a three-dimensional structure
capable of performing a specific task.
In the 1960s, hemoglobin was all the rage in biological research.
Haemoglobin's job is to carry oxygen from the lungs through the blood to all the tissues in the body so cells can do their
version of breathing.
Researchers discovered that there is more than just one type of hemoglobin and that some haemoglobins are linked to
disease. Sickle cell anaemia, for example, is caused by a mutation in the hemoglobin gene that results in a malformed
protein. The discovery of sickle cell hemoglobin, named hemoglobin S, set off a race to find additional versions of
hemoglobin related to human disease.
In 1968 Samuel Rahbar recognizes that hemoglobin A1C is elevated in people with diabetes.
Scientist Rahbar called this “The diabetic component of hemoglobin."

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What Is It
Scientists around the world were studying hemoglobin using a different separation method called chromatography.
They soon discovered several subtypes of hemoglobin A. "They could see a big peak of hemoglobin A, and all these little
peaks,“
In those little peaks were five new haemoglobins named A1a, A1b, A1c, A1d, and A1e, based on the order in which they
emerged from the chromatograph.
Rahbar found that the A1C molecule made up from 7.5 to 10.6 percent of the total hemoglobin in people with diabetes,
while it constituted only 4 to 6 percent of hemoglobin in those without the disease, again establishing the link between the
A1C molecule and diabetes.
Chemically, it differed from plain hemoglobin A.
They discovered that the A1C molecule was essentially hemoglobin A—they have the same sequence of amino acids—but
with one critical difference: a glucose molecule stuck to one end.

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The number of hemoglobin A proteins that become tethered to a glucose molecule, forming the A1C molecule, is
proportional to the concentration of glucose in the blood.
The A1C was a game changer because it reported on the average blood glucose over two to three months (because the
lifetime of a red blood cell is about two to three months). Before the A1C test, patients could eat well and exercise for two
days before an exam and get a stellar blood glucose result.
In 1975 Anthony Cerami and colleagues suggest that A1C is related to blood glucose control.
In the late 1970s, companies developed the first commercial tests of hemoglobin A1C
A1C was much, much better than self-monitoring" at predicting who was at high risk for diabetes complications
A1C as the gold-standard marker of long-term health in people with type 1 diabetes.
People with diabetes maintain an A1C of 7 percent or less.
People with diabetes have an A1C blood test two to four times a year. Doctors and patients use the number to make
decisions about medication selections and dosages and to assess the effects of lifestyle changes on blood glucose levels.

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In 1980 The American Diabetes Association first recommends A1C Tests
Blood glucose varies a lot over the course of a day, and even testing with a meter several times a day doesn't provide a
complete picture.
Then came Continuous Glucose Monitors (CGMs), which test glucose levels every few minutes.
Researchers finally had a way to see if A1C coincided with average blood glucose.
In 1993 The Diabetes Control and Complications Trial establishes A1C as a valuable clinical marker in people with type
1 diabetes.
In a 2008 study, 507 people, some with type 1 or type 2 diabetes and others without the disease, wore CGMs for three
months. The researchers used the 2,700 glucose measurements they obtained from each participant during that time to
calculate his or her average blood glucose, then compared the value to the measured A1Cs. The average glucose levels
aligned with the A1Cs, showing the A1C test's validity. Now, A1C test results can be translated in terms of an estimated
average glucose
HbA1c is a useful indicator of how well the blood glucose level has been controlled in the recent past (over two to three
months) and may be used to monitor the effects of diet, exercise, and drug therapy on blood glucose in people with
diabetes.

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In 1998 The United Kingdom Prospective Diabetes Study establishes A1C as a valuable clinical marker in people with
type 2 diabetes.
Translating A1C
The A1C is a measure of average blood glucose over the previous two to three months.
The chart below gives the estimated average glucose for a given A1C, in the same units
seen on a blood glucose meter.
A1C (%)
5% 6% 7% 8% 9% 10% 11% 12%
97mg/dl 126mg/dl 154mg/dl 183mg/dl 212mg/dl 240mg/dl 269mg/dl 298mg/dl
(eAG) Estimated Average Glucose (mg/dl)
It is recommend using it to diagnose diabetes and prediabetes .
An A1C of below 5.7 percent is considered normal, while A1C levels of 6.5 percent and above call for a diagnosis of
diabetes. Levels between those two percentages signal prediabetes.
In 2010 The American Diabetes Association recommends using the A1C to diagnose diabetes and prediabetes.

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HbA1C is the measures the amount of glucose attached to a protein called Hemoglobin.
ADA standards consider A1C values less than 7% as a satisfactory control for people for diabetes.
A1C fluctuated proportionately with fasting, postprandial and mean glucose over the past 8-12 weeks.
Intensive treatment to achieve A1C goals are associated with decreased diabetes complications in patients with type 1 or
type 2 diabetes.
Hemoglobin is the oxygen-carrying pigment that gives blood its red color and is also the predominant protein in red
blood cells.
About 90% of hemoglobin is hemoglobin A (the "A" stands for adult type).
Although one chemical component accounts for 92% of hemoglobin A, approximately 8% of hemoglobin A is made up
of minor components that are chemically slightly different.
These minor components include hemoglobin A1c, A1b, A1a1, and A1a2. Hemoglobin A1c (HbA1c) is a minor
component of hemoglobin to which glucose is bound.
HbA1c also is sometimes referred to as glycosylated or glycosylated hemoglobin or glycohemoglobin.

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Most Asked Questions About Diabetes
What is Diabetes?
Diabetes is a disease.
Can you ‘catch’ diabetes?
No
At what age do you get diabetes?
Anyone can get diabetes at any age
What type of people get diabetes?
Anyone may develop diabetes
How can I tell if I have diabetes
The symptoms of diabetes include:

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 Feeling Tried
Passing Urine Frequently
Feeling Constantly Thirsty
Blurredvisionitching of the skinor genital area
Slowhealing infections
Numbness and tingling in the hands of feet
Sometimes these problems come quickly, other times slowly.
People with type 2 diabetes oftenfeel unwell for long periods without knowing
Why?

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Can Diabetes be cured?
As yet thereis no cure. However, excellent treatment is available.
Diabetes can’t be cured; however it can be managed throughlifestyle, tablets or
insulinalong withhelp and advice fromyour doctor and other health professionals.
Perform the A1C test at least two times a year in patients who are meeting treatment goals (and who
have stable glycemic control). Perform the A1C test quarterly in patients whose therapy has changed or
who are not meeting glycemic goals. A1C testing should be performed routinely in all patients with
diabetes. The frequency of A1C testing should be dependent on the clinical situation, the treatment
regimen used, and the clinician’s judgment. Some patients with stable glycemia well within target may
do well with testing only twice per year. Unstable or highly intensively managed patients (e.g.,
pregnant type 1 diabetic women) may require testing more frequently than every 3 months.

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Red Blood Cells are freely permeable to glucose
molecules
Glucose irreversibly attaches to hemoglobin to
form Glycated hemoglobin (HbA1c)
Because Red Blood Cells have a life span of 120
days, glycated hemoglobin reflects glucose levels
over the preceding 2-3months
The HbA1c fraction is abnormally elevated in
people with chronic hyperglycemia
A HbAlc >6.5% is diagnostic of diabetes if
confirmed by repeat testing

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Prepared By
Sakshi Dubey
sakshikumaridubey@gmail.com