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Glycosylated hemoglobin and the risk of chronic complications

Author: Dr Sorin Ioacara, MD, PhD
Last Updated on
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Discover here: Normal HbA1c values | Correct measurement | When it is not useful

Glycosylated hemoglobin (HbA1c) is the percentage of “anemia” hemoglobin that has “sugared” as a result of exposure to blood glucose. HbA1c is the official abbreviation for glycosylated hemoglobin.

“Anemia” hemoglobin is a protein located inside the red blood cells. Its role is to transport oxygen from the lungs to the tissues and CO2 from the tissues to the lungs. The decrease in hemoglobin blood concentration is called anemia.

Glucose usually present in the blood continuously sticks to hemoglobin. This also happens in healthy people without diabetes. Glucose binding to hemoglobin yields glycosylated hemoglobin. A synonym for glycosylated hemoglobin is glycated hemoglobin.

What is the normal glycosylated hemoglobin level?

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Normal glycosylated hemoglobin values are below 5.7% (39 mmol/mol). In the presence of higher blood sugar, it exceeds this amount. For values of 5.7-6.4% (39-47 mmol/mol) the patient is in the prediabetes area. Starting with 6.5% (48 mmol/mol) we enter the field of diabetes. What happens if the HbA1c value is high? Beginning with 7% (53 mmol/mol), the risk of developing chronic complications of diabetes increases significantly. For this reason, the target of glycosylated hemoglobin is below 7% (53 mmol/mol).

For reference, a glycosylated hemoglobin value of 7% (53 mmol/mol) corresponds to an average of all blood glucose levels of approximately 150 mg/dl (8.3 mmol/l). You can find the correspondence between various HbA1c values and mean blood glucose levels on the WebMD website.

HbA1c targets may be reduced to <6.5% (48 mmol/mol) in young patients without complications, if you can obtain them without an increased risk of hypoglycaemia. Time spent in hypoglycaemia should be less than 4% of the total.

For the same value of HbA1c, the time spent in normoglycemia matters a lot, i.e. between 70-180 mg/dl (3.9-10 mmol/l). This time must be over 70% of the analyzed period.

How is glycosylated hemoglobin measured correctly?

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HbA1c should be measured using a recognized and calibrated method (DCCT standard). The HbA1c dosing from the finger has the lowest measurement accuracy of all available options. The HPLC method has the best precision. On your test report, you will also find the analysis method. The HPLC method is the only one that accurately measures HbA1c. All other techniques dose HbA1c together with different other types of hemoglobin and estimate (bet) the HbA1c result if only it had been measured. The HPLC method is more expensive and therefore, more readily available.

Unexpected differences between HbA1c and plasma blood glucose levels should raise suspicion of laboratory kit malfunctions. These errors can sometimes occur due to the existence of unique variants of hemoglobin in the patient’s blood (hemoglobinopathies).

In this case, you should use a laboratory kit capable of providing a correct measurement even in such conditions (HPLC analyzer). The alternative is to use only plasma blood glucose for the diagnosis and follow-up of diabetes, not HbA1c.

When we must not rely on glycosylated hemoglobin

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HbA1c cannot be used to diagnose and monitor the treatment of diabetes in conditions associated with a rapid change in red blood cells. These conditions generally occur when there is a very high production and a very high destruction of red blood cells. The average lifespan of red blood cells is 120 days. Hence the three-month estimate of metabolic control by HbA1c. Consequently, any reduction in the life of red blood cells (e.g. pregnancy) is associated with metabolic control estimation for less than three months.

At their birth in the bone marrow, red blood cells have non-glycosylated hemoglobin. Consequently, if you suddenly have a lot of newly-born red blood cells, they will quickly dilute the amount of glycosylated hemoglobin. The reason is that glycosylated hemoglobin can exist only in mature red blood cells. Thus, there is a false decrease in the value of HbA1c, which will underestimate the quality of metabolic control.

The main situations in which glycosylated hemoglobin is not relevant are the following:

  1. Siclemia (a form of anemia)
  2. Iron deficiency anemia
  3. Pregnancy in trimesters 2 and 3
  4. Hemodialysis
  5. Recent blood loss
  6. Recent blood transfusion
  7. Erythropoietin treatment
  8. Diagnosis of type 1 diabetes with acute onset
  9. Diagnosis of diabetes associated with cystic fibrosis

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