Limits of Glycated Hemoglobin and the Importance of Other Glycated Proteins
Glycated hemoglobin is a gold standard in the diagnosis and management of diabetes treatment. However, its disadvantages include numerous factors that can cause false increases or decreases in its levels. Therefore, the scientific community is also interested in researching other glycated proteins that could be used in diabetes control. So, what should we keep in mind when collecting glycated hemoglobin?
What influences glycation?
Glycation is a non-enzymatic binding of sugar to proteins, forming fructosamine.
Factors that influence non-enzymatic protein glycation:
- concentration of carbohydrates and proteins and their fluctuations in the blood
- biological half-life of a given protein
- temperature
Glycated Hemoglobin
Types of Hemoglobin
95% of hemoglobin in adults is composed of hemoglobin HbA, 2-3% hemoglobin HbA2, and less than 2% fetal hemoglobin HbF. Hemoglobin HbA is further divided into non-glycated and glycated components. 94% of hemoglobin HbA is non-glycated hemoglobin, labeled as HbA0. Glycated hemoglobin, known as HbA1, is further divided into HbA1a, HbA1b, and HbA1c. The latter is the main hemoglobin used in monitoring diabetes mellitus.
Practical Advantages of Glycated Hemoglobin over Glycemia
- Glycated hemoglobin represents a long-term average of individual glycemias over the period of 8-12 weeks before blood collection.
- The patient does not need to be fasting for the blood draw. Laboratories recommend that the patient be at rest for about 15 minutes before the draw.
Factors Influencing HbA1c Values
Factors that can increase HbA1c levels:
- polycythemia
- iron deficiency anemia (increase in HbA1c of up to 2%, can be reversed with iron supplementation)
- folic acid or vitamin B12 deficiency anemia
- post-splenectomy state
- renal insufficiency
- hypertriglyceridemia
- hyperbilirubinemia
- chronic alcoholism
- aspirin use
- opioid use
Factors that can decrease HbA1c levels:
- thalassemia
- spherocytosis
- hemolytic anemia
- hemorrhagic conditions
- severe burns with loss of fluids and proteins
- lead poisoning
- secondary erythropoietin deficiency following renal failure
- multiple myeloma
- leukemia
- hyperthyroidism
- vitamin C use
- vitamin E use
Limits of Glycated Hemoglobin Determination
Determination of glycated hemoglobin values is a gold standard in diagnosing and monitoring diabetes compensation. However, with significant changes in erythrocyte lifespan, the reliability of its determination is significantly reduced, and the clinical effectiveness of measurement results can be notably limited.
Other Glycated Proteins
In cases where factors affecting the standard lifespan of erythrocytes are present, there are increasing opinions about the advantage of using glycated albumin or glycated fructosamine as a mid-term indicator of blood glucose concentration.
Glycated Albumin (GA)
The half-life of albumin is 15 days. GA levels correlate with average glucose values over the past 2-3 weeks. The advantage is that its levels are not affected by the lifespan of erythrocytes or erythropoietin therapy. On the other hand, its values can be distorted by age, nutritional status, albuminuria, liver cirrhosis, thyroid dysfunction, or smoking. GA is also indirectly affected by body mass index and the amount of adipose tissue. Nonetheless, glycated albumin appears to be a better marker that reflects the accuracy of glycemia control compared to HbA1c in patients with chronic kidney disease.
Glycated Fructosamine
The determination of glycated protein—fructosamine—appears to be clinically less effective. Fructosamine levels reflect average glucose levels over the previous 10-14 days. Because it measures total glycated serum proteins, of which glycated albumin accounts for approximately 90%, fructosamine concentrations can be influenced by the concentrations of various serum proteins. Fructosamine is further influenced by bilirubin, urea, and uric acid levels.
1,5-anhydroglucitol (1,5-AG)
1,5-AG is a glucose analog found in plasma after food intake. It is a short-term marker; 1,5-AG values reflect hyperglycemia over approximately 1 week.
Conclusion
Current data do not suggest that other glycated proteins will replace HbA1c testing in the future, but they could play an adjunctive role in diabetes control.
(tich)
Sources:
1. Pecoits-Filho R., Abensur H., Betônico C. C. et al. Interactions between kidney disease and diabetes: dangerous liaisons. Diabetol Metab Syndr 2016; 8: 50, doi: 10.1186/s13098-016-0159-z.
2. Breinek P. Glycated hemoglobin A1c. Masaryk University, Brno, 2014. Available at: https://is.muni.cz/el/med/podzim2014/BLKKB0321p/HbA1c_2014.pdf
3. Glycated hemoglobin (HbA1c) in blood. Thomayer University Hospital. Available at: www.ftn.cz/upload/ftn/Kliniky/okb/Dokumenty/prirucka/_LP_15194-L0000013.htm
4. Friedecký B., Kratochvíla J. Glycated albumin in blood serum/plasma. A brief overview of the current state. Clinical Biochemistry and Metabolism 2018; 26 (2): 79-81.
Did you like this article? Would you like to comment on it? Write to us. We are interested in your opinion. We will not publish it, but we will gladly answer you.
