December 1, 2022Chemical pathologyLab Tests
HbA1c (Glycosylated Hemoglobin)
Sample for HbA1c (Glycosylated Hemoglobin)
- The blood sample is taken in the EDTA.
- Washed RBC or hemolysate is prepared stable for 4 to 7 days at 4 °C.
- 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)
- This test is used to monitor diabetes control.
- This test shows the patient’s average glucose index over a long time (2 to 3 months).
- The index of diabetic control gives a direct relationship between poor control and the development of complications.
- It tracks glucose in the milder form of diabetes.
- It helps to determine which type of drugs may be needed.
- Predict the development and progression of diabetic microvascular complications.
- 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.
- It should be repeated every 3 to 4 months (some advise 2 to 3 months).
Definition of HbA1c (Glycosylated Hemoglobin)
- Glucose combine with hemoglobin continuously and irreversibly during the life span of RBC (120 days).
- The HbA1c will be proportional to the mean blood glucose level during the last 6 to 12 weeks.
Advantage of HbA1c (Glycosylated Hemoglobin)
- The sample can be drawn at any time.
- This test is not affected by short-term variations like:
- Hypoglycemic agents.
- Patient attitude or cooperation.
- It differentiates short-term hyperglycemia in nondiabetic patients like:
- Recent stress.
- Myocardial infarction.
- Gives information on glucose imbalance in a patient with mild diabetes mellitus.
- 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.
- Evaluating the success of diabetic treatment and patient compliance.
Limitation of HbA1c (Glycosylated Hemoglobin):
- This can not be used to find a day-to-day glucose fluctuation to adjust the insulin dose.
- It can not find a day-to-day presence of hypo or hyperglycemia.
Pathophysiology of HbA1c (Glycosylated Hemoglobin):
- In adults, hemoglobin is:
- Hemoglobin A is 98%.
- HbA2 is around 2.5%.
- HbF is 0.5%.
- Now 7% of hemoglobin A consists of hemoglobin A1.
- Glucose is attached to the terminal valine amino acid of the globulin β-chain. This process is called glycosylation.
- This hemoglobin A1 combines strongly with glucose through the process called glycosylation, called hemoglobin A1 (HbA1).
- The glycosylation process takes place when RBCs are exposed to glucose.
- Hemoglobin and glucose form a bond. Initially, it is labile; then, it becomes stable. It is very slowly and poorly reversible.
- Hemoglobin A1 consists of the following:
- HbA1c combines more strongly with glucose.
- HbA1c is 70% glycosylated.
- While HbA1a and HbA1b are only 20% glycosylated.
- If we measure total HbA1, the values are 2 to 4% higher than the HbA1c.
- The amount of glycohemoglobin depends upon the glucose concentration available in the circulation and the life span of RBCs which is 120 days.
- Therefore, glycohemoglobin estimates glucose over 100 to 120 days.
- Glycohemoglobin concentration depends upon the exposure of glucose to the RBCs.
- HbA1c may not reflect the recent change in glucose level.
- Glycohemoglobin is a normal, minor type of hemoglobin. This is blood glucose bound to hemoglobin.
- In the presence of hyperglycemia, an increase in glycohemoglobin causes an increase in the Hb A1c.
- When a measurable increase in the glycosylated or stable hemoglobin begins, it will appear in 2 to 3 weeks.
- Glycosylated hemoglobin reflects the average blood glucose level for a 2 to 3 months period before the test.
- 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|
- HbA1 c (% of total Hb) = 4.0 to 5.2
- Hb A1 (% of total Hb) = 5.0 to 7.5
- Non-Diabetic adults = 2.2 to 4.8 %.
- Non-Diabetic child = 1.8 to 4.0 %.
- Prediabetic = 5.7 to 6.4 %
- Diabetics = >6.5 %
- Diabetic HbA1c = > 8.1 % = corresponds with glucose >200 mg/dl.
Diabetic control and HbA1c:
- Good diabetic control = 2.5 to 5.9 %.
- Fair diabetic control = 6 to 8 %.
- Poor diabetic control = > 8 %.
- (Values may vary according to the lab)
- Another source
- Good diabetic control = <7%
- Fair diabetic control = 10%
- 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 :
HbA1c and recommendation for the treatment of diabetic patients:
|HbA1c level||Glucose mg/dL||Glucose mmol/L||Interpretations/recommendations|
HbA1c and estimated blood glucose level:
|HbA1c level||Glucose level mg/dL|
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:
- Newly diagnosed diabetic patient.
- Uncontrolled diabetic patient.
- Nondiabetic hyperglycemia is seen in:
- Cushing’s syndrome.
- Corticosteroids therapy.
- Acute stress.
- Patient with splenectomy.
- Alcohol toxicity.
- Iron deficiency anemia.
- Lead toxicity.
- Opiates toxicity.
- Chronic renal failure with or without hemodialysis.
- Salicylates treatment.
The decreased HbA1c level is seen in the following:
- Hemolytic anemia.
- After a blood transfusion.
- Chronic blood loss.
- Vitamin C or E intake in excess.
False raised level of HbA1c may be seen in the following conditions:
- Renal failure.
- Raised level of triglycerides (hypertriglyceridemia).
- In Chronic Alcoholics.
HbA1c can be controlled or lowered by:
- Diet control.
- Or a combination of these.
The significance of HbA1c in diabetic patients:
- The incidence of retinopathy increases in patients with an HbA1c level between 6.0 to 7.0%
- Fewer chances for retinopathy when the HbA1c level is <6.5%.
- HbA1c level in diabetic patients is recommended at <7.0%.
- HbA1c should be checked at least twice a year.
- 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:
- Reducing the weight of about 7% of your body weight.
- Exercise like brisk walking for 30 minutes, 5 days a week.
Questions and answers:
Question 1: Which glycosylated hemoglobin has more binding with the glucose?
Glycosylated hemoglobins are HbA1a, HbA1b. and HbA1c; out of these, HbA1c has more binding with the hemoglobin, so we measure HbA1c. When we say total glycosylated hemoglobin, we mean HbA1a + HbA1b + HbA1c.
Question 2: What is the recommendation of the HbA1c for diabetic patients?
Diabetic patients have good control when the HbA1c is <7.0.