HbA1c (Glycosylated Hemoglobin), Glycohemoglobin (G-Hb), Glycated Hemoglobin, Diabetic control index

Sample

1. The blood sample is taken in the EDTA 3 to 4 ml.
2. Washed RBC or hemolysate is prepared and this is 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 average glucose index over a long period of time (2 to 3 months).
3. It tracks glucose in the milder form of diabetes.
4. It helps to determine which type of drugs may be needed.
5. Its measurement is of value in a specific group of patients like:
   • Diabetic children
   • Diabetic patients whose renal threshold for glucose is abnormal.
   • Unstable diabetes type I, taking insulin.
   • Type II diabetic women who become pregnant.
   • Patients with changing dietary or other habits.
6. It should be repeated every 3 to 4 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. Evaluating the success of diabetic treatment and patient compliance.

Limitation of HbA1c

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

pathophysiology

1. In the adult, 98% of the Hemoglobin is hemoglobin A.
2. Now 7% of hemoglobin A consists of hemoglobin A1.
   1. HbA + glucose ⇔ Pre HbA1c  → HbA1c
3. This hemoglobin A1 combines strongly with glucose by the process called glycosylation.
4. Hemoglobin A1 consists of :
   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%.

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

Normal

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)

Mean Plasma glucose:

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

• The formula is as follows :
• 

  Mean plasma glucose calculation

The following table gives a recommendation for the treatment:

HbA1c level	mg/dL	mmol/L	Interpretation
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 = mg/dL /18 = mmol/L

                    mmol/L  x 18 = 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. This is suggested that HbA1c level above 6.5% favor diabetes mellitus.

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

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

 

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