HbA1c (Glycosylated Hemoglobin)

Sample for HbA1c (Glycosylated Hemoglobin)

1. The blood sample is taken in the EDTA.
2. Washed RBC or hemolysate is prepared stable for 4 to 7 days at 4 °C.
3. A blood sample can be drawn at any time. No need for fasting or dietary need.

Purpose of the test (Indications) of HbA1c (Glycosylated Hemoglobin)

1. This test is used to monitor diabetes control.
2. This test shows the patient’s average glucose index over a long time (2 to 3 months).
3. The index of diabetic control gives a direct relationship between poor control and the development of complications.
4. It tracks glucose in the milder form of diabetes.
5. It helps to determine which type of drugs may be needed.
6. Predict the development and progression of diabetic microvascular complications.
7. Its measurement is of value in a specific group of patients like:
   1. Diabetic children.
   2. Diabetic patients whose renal threshold for glucose is abnormal.
   3. Unstable diabetes type I, taking insulin.
   4. Type II diabetic women who become pregnant.
   5. Patients with changing dietary or other habits.
8. It should be repeated every 3 to 4 months (some advise 2 to 3 months).

Definition of HbA1c (Glycosylated Hemoglobin)

1. Glucose combine with hemoglobin continuously and irreversibly during the life span of RBC (120 days).
2. The HbA1c will be proportional to the mean blood glucose level during the last 6 to 12 weeks.

Advantage of HbA1c (Glycosylated Hemoglobin)

1. The sample can be drawn at any time.
2. This test is not affected by short-term variations like:
   1. Food.
   2. Exercise.
   3. Hypoglycemic agents.
   4. Stress.
   5. Patient attitude or cooperation.
3. It differentiates short-term hyperglycemia in nondiabetic patients like:
   1. Recent stress.
   2. Myocardial infarction.
4. Gives information on glucose imbalance in a patient with mild diabetes mellitus.
5. It may rise within one week after the rise in blood glucose due to stopping the therapy. It will not fall for 2 to 4 weeks after blood glucose decreases when treatment starts again.
6. Evaluating the success of diabetic treatment and patient compliance.

Limitation of HbA1c (Glycosylated Hemoglobin):

1. This can not be used to find a day-to-day glucose fluctuation to adjust the insulin dose.
2. It can not find a day-to-day presence of hypo or hyperglycemia.

Pathophysiology of HbA1c (Glycosylated Hemoglobin):

1. In adults, hemoglobin is:
   1. Hemoglobin A is 98%.
   2. HbA2 is around 2.5%.
   3. HbF is 0.5%.
   4. Now 7% of hemoglobin A consists of hemoglobin A1.
2. Glucose is attached to the terminal valine amino acid of the globulin β-chain. This process is called glycosylation.

3. This hemoglobin A1 combines strongly with glucose through the process called glycosylation, called hemoglobin A1 (HbA1).
   1. The glycosylation process takes place when RBCs are exposed to glucose.
   2. Hemoglobin and glucose form a bond. Initially, it is labile; then, it becomes stable. It is very slowly and poorly reversible.

HbA1c (Glycosylated Hemoglobin): Glycosylation and formation of HbA1c

4. Hemoglobin A1 consists of the following:
   1. HbA1a
   2. HbA1b
   3. HbA1c
5. HbA1c combines more strongly with glucose.
   1. HbA1c is 70% glycosylated.
   2. While HbA1a and HbA1b are only 20% glycosylated.

6. If we measure total HbA1, the values are 2 to 4% higher than the HbA1c.
7. The amount of glycohemoglobin depends upon the glucose concentration available in the circulation and the life span of RBCs which is 120 days.
   1. Therefore, glycohemoglobin estimates glucose over 100 to 120 days.
   2. Glycohemoglobin concentration depends upon the exposure of glucose to the RBCs.
8. HbA1c may not reflect the recent change in glucose level.
   1. Glycohemoglobin is a normal,  minor type of hemoglobin. This is blood glucose bound to hemoglobin.
   2. In the presence of hyperglycemia, an increase in glycohemoglobin causes an increase in the Hb A1c.
   3. When a measurable increase in the glycosylated or stable hemoglobin begins, it will appear in 2 to 3 weeks.
9. Glycosylated hemoglobin reflects the average blood glucose level for a 2 to 3 months period before the test.
10. Glycated hemoglobin concentration reflects the mean blood glucose level concentration over the last 4 to 8 weeks.

Role of HbA1c in Diabetics

HbA1c positivity rate:

Normal HbA1c

Source 1

• HbA1 c (% of total Hb) = 4.0 to 5.2
• Hb A₁  (%  of  total Hb) ₌ 5.0 to  7.5

Source 2

1. Non-Diabetic adults = 2.2 to 4.8 %.
2. Non-Diabetic child = 1.8 to 4.0 %.
   1. Prediabetic              = 5.7 to 6.4 %
   2. Diabetics                  = >6.5 %
   3. Diabetic HbA1c = > 8.1 % = corresponds with glucose >200 mg/dl.

Diabetic control and HbA1c:

1. Good diabetic control = 2.5 to 5.9 %.
2. Fair diabetic control = 6 to 8 %.
3. Poor diabetic control = > 8 %.
   • (Values may vary according to the lab)
4. Another source
   1. Good diabetic control = <7%
   2. Fair diabetic control = 10%
   3. poor diabetic control = 13% to 20%

Mean Plasma glucose:

• It is a mathematical calculation where HbA1c (Glycosylated Hemoglobin) and Glycated Hb can be correlated with daily mean plasma glucose level (MPG).
• • The formula is as follows :

The formula of mean plasma glucose

HbA1c and recommendation for the treatment of diabetic patients:

HbA1c and estimated blood glucose level:

Formula = Glucose in mg/dL /18 = Glucose in mmol/L

                    Glucose in mmol/L  x 18 = Glucose in mg/dL

The HbA1c Increased level is seen in:

1. Newly diagnosed diabetic patient.
2. Uncontrolled diabetic patient.
3. Nondiabetic hyperglycemia is seen in:
   1. Cushing’s syndrome.
   2. Acromegaly.
   3. Corticosteroids therapy.
   4. Pheochromocytoma.
   5. Acute stress.
   6. Glucagonoma.
4. Patient with splenectomy.
5. Alcohol toxicity.
6. Iron deficiency anemia.
7. Lead toxicity.
8. Opiates toxicity.
9. Chronic renal failure with or without hemodialysis.
10. Salicylates treatment.

The decreased HbA1c level is seen in the following:

1. Hemolytic anemia.
2. Hemoglobinopathies.
3. After a blood transfusion.
4. Chronic blood loss.
5. Vitamin C or E intake in excess.
6. Pregnancy.

False raised level of HbA1c may be seen in the following conditions:

1. Renal failure.
2. Raised level of triglycerides (hypertriglyceridemia).
3. In Chronic Alcoholics.

HbA1c can be controlled or lowered by:

1. Exercise.
2. Diet control.
3. Medication.
4. Or a combination of these.

The significance of HbA1c in diabetic patients:

1. The incidence of retinopathy increases in patients with an HbA1c level between  6.0 to 7.0%
2. Fewer chances for retinopathy when the HbA1c level is <6.5%.
3. HbA1c level in diabetic patients is recommended at <7.0%.
4. HbA1c should be checked at least twice a year.
5. It is suggested that HbA1c levels >6.5% favor diabetes mellitus.

Diabetes type II risk can be lowered by around 58% of the cases by:

1. Reducing the weight of about 7%  of your body weight.
2. Exercise like brisk walking for 30 minutes, 5 days a week.

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