HbA1c (Glycosylated Hemoglobin)

Sample

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.

Purpose of the test (Indications)

1. This test is used to monitor diabetes control.
2. This test tells us the patient’s average glucose index over a long time (2 to 3 months).
3. 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 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).

Advantage of HbA1c

1. The sample can be drawn at any time.
2. This test is not affected by short-term variation 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 stoping 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

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

1. In adults, 98% of the hemoglobin is hemoglobin A. While HbA2 is around 2.5% and HbF is 0.5%.
2. Now 7% of hemoglobin A consists of hemoglobin A1.
3. Glucose is attached to the valine amino acid of β-globulin of the hemoglobin molecule; this process is called glycosylation.
   

   Hb A1c formation

4. This hemoglobin A1 combines strongly with glucose by the process called glycosylation.
   

   Glycosylation and formation of HbA1c

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

      HbA1c synthesis

7. If we measure total HbA1, the values are 2 to 4% higher than the HbA1c.
8. The amount of glycohemoglobin depends upon the glucose concentration available in the circulation and life span of RBCs which is 120 days.
   1. Therefore, glycohemoglobin estimates glucose over a period of 100 to 120 days.
   2. Glycohemoglobin concentration depends upon the exposure of glucose to the RBCs.
9. 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.
10. Glycosylated hemoglobin reflects the average blood glucose level for a 2 to 3 months period before the test.
11. Glycated hemoglobin concentration reflects the mean blood glucose level concentration over the last 4 to 8 weeks.

HbA1c positivity rate:

Blood glucose level	Positivity of HbA1c
Fasting Glucose <110 mg/dL	HbA1c Normal in>96% of the cases
Fasting Glucose 110 to 125 mg/dL	HbA1c Normal in >80% of the cases
Fasting glucose >126 mg/dL	HbA1c Normal in >60% of the cases

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 adult = 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 mathematical calculations where Glycated Hb can be correlated with daily mean plasma glucose level (MPG).

• • The formula is as follows :

HbA1c and recommendation for the treatment of diabetic patients:

HbA1c level	Glucose mg/dL	Glucose mmol/L	Interpretations/recommendations
4	65	3.6	non-diabetic
5	100	5.55	non-diabetic
6	135	7.5	non-diabetic
7	170	9.5	ADA target
8	205	11.5	treatment needed
9	240	13.5	treatment needed
10	275	15.5	treatment needed
11	269	14.9	treatment needed
12	298	16.5	treatment needed
13	326	18.0	treatment needed
14	355	19.7	treatment needed

HbA1c and estimated blood glucose level:

HbA1c level	Glucose level  mg/dL
4%	65
5%	100
6%	126
7%	154
8%	185
9%	212
10%	240
11%	270
12%	300
19.4%	350
22.2%	400
24.9%	450
27.7%	500

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.

The decreased HbA1c level is seen in:

1. Hemolytic anemia.
2. Chronic blood loss.
3. Chronic renal failure.
4. 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  recommended <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.

 

---