The hemoglobin A1c (glycated hemoglobin, glycosylated hemoglobin, HbA1c, or A1c) test is used to evaluate a person's level of glucose control. The test shows an average of the blood sugar level over the past 90 days and represents a percentage. The test can also be used to diagnose diabetes.
Hemoglobin is a protein only found in red blood cells. In fact, hemoglobin is what gives blood its bright red coloring. Since red blood cells live about an average of three months, the A1c test will reflect those red blood cells that are present in the bloodstream at the time of the test; this is why the A1c serves as an average of blood sugar control.
The main job of hemoglobin is to carry oxygen from the lungs to all the cells of the body. Hemoglobin becomes glycated or coated with glucose from the bloodstream. The amount of glucose that is present in the blood will attach to the hemoglobin protein, and increased glucose levels will reflect on the surface of the hemoglobin protein, thereby rendering a higher A1c level.
The Diabetes Control and Complications Trial (DCCT) was a landmark trial that provided a wealth of data on A1c and its correlation to blood glucose levels, as well as establishing specific treat to target A1c goals. From the completion of the trial, the National Glycohemoglobin Standardization Program (NGSP) was formed to define a standardized assay that was usable across laboratories.
The DCCT trial reported that a higher mean A1c level was the dominant predictor of diabetic retinopathy progression. In addition to the determination of A1c levels predicting progression of retinopathy, the trial also found that a 10% decrease in A1c can lower the risk of retinopathy progression from 43% to 45%. Additionally, if the A1c level is decreased by 1% overall, there is a critical effect on the progression of diabetic retinopathy.
People with diabetes need to have their A1c checked regularly to determine if their average blood glucose levels are within the target range.
The A1c test can either be done as a point of care (POC), STAT test, or by sending a sample to a laboratory. The POC test uses a STAT analyzer that evaluates the A1c from a capillary fingerstick. The laboratory test uses about a teaspoon of blood drawn from a venous sample into a K2 EDTA (lavender top) tube. The sample gets processed as whole blood.
Using A1c as a diagnostic tool
The venous sample A1c test may be used as a diagnostic tool in clinical practice when determining diabetes risk or onset. Due to the variability of capillary point of care testing, any A1c done by capillary sample should be confirmed with a venous sample before rendering the diagnosis.
For an A1c test to classify as normal, or in the non-diabetic range the value must be below 5.7 %. Anyone with an A1c value of 5.7 % to 6.4 % is considered to be prediabetic, while diabetes can be diagnosed with an A1c of 6.5% or higher.
Tests should be sent to a laboratory certified by the NGSP to ensure results are standardized.
The A1c test done by a point of care machine in a doctor's office may be less accurate than one that is drawn from a venous sample and processed in a laboratory. Typically, the results can vary by different laboratories by as much as 0.5%.
The A1c test should be performed using an NGSP-approved method.
There are several conditions where the A1c test can produce inaccurate results. People diagnosed with sickle cell anemia, thalassemia, anemia, kidney failure, liver disease, or patients receiving blood transfusions can experience altered results due to the longevity of the red blood cell. A1c test in these patients must be interpreted with caution and should be confirmed with plasma glucose samples to diagnose diabetes.
A falsely low A1c value can result from several conditions including high altitude, pregnancy, hemorrhages, blood transfusions, erythropoietin administration, iron supplementation, hemolytic anemia, chronic kidney failure, liver cirrhosis, alcoholism, folic acid deficiency, sickle cell anemia, and spherocytosis. One the other end of the spectrum, a falsely high A1c be due to a lack of available iron in the blood. This condition can result from iron deficiency anemia, infection-induced anemia, or tumor-induced anemia. Hemoglobinopathies such as thalassemia can also cause a falsely high A1c. Other causes of false high A1c levels include hypertriglyceridemia, organ transplantation, and hyperglycation in certain ethnic groups. Medications such as immunosuppressants and protease inhibitors can sometimes lead to a falsely high A1c.
Relationship Between A1c and Glucose Level
The A1c percentage equates to an average glucose level in the body that the patient experienced over the past 90 days.
A1c (%) Average Blood Glucose (mg/dL)
Hemoglobin A1c serves as an indicator of overall glycemic control and a reflection of the average blood sugar over the past three months.
Laboratories can use several methods to determine A1c. High-performance liquid chromatography (HPLC) method is one of the more popular methods because the method eliminates labile components that other methods such as immunoassay or affinity chromatography.
Point of care machines is widely used as well to determine A1c levels. The variety of POC machines on the market can make it difficult to determine the one best suited for one's practice. Also, there is a shortage of information comparing the different machines. When using POC testing, one should keep in mind that POC values are often below results reported by a laboratory test, with the mean difference being -0.5%.
All clinicians who look after diabetic patients need to know what A1c means. In general, A1c provides a measure of the glucose concentration over three months.
Hemoglobin A1c is often used as an outcome measure to determine if an intervention in a population is successful by showing a decrease in A1c by a certain percentage. There is a movement within the diabetes community to move away from using A1c as a standard to measure patient response to treatment. The Estimated Average Glucose (eAG) is the newest proposed method. This method uses data obtained by continuous glucose monitors (CGMs) that record blood glucose 24 hours a day. This method gives providers a more accurate view of the blood sugar average and fluctuations, but the method is not available to all patients on a wide-spread basis.
Levels of A1c should be measured twice a year in stable patients and at least four times in patients who have glucose fluctuations or those who have had a change in their diabetic treatment. A1c is the preferred diabetes diagnostic test today. The blood draw can occur at any time, and there are no special handling requirements. However, to ensure that the A1c value is correct, clinicians need to be aware of the causes of false-positive and false-negative results.
Since many diabetic patients have their condition managed in outpatient clinics, the diabetic nurse should be fully aware of A1c values and when to refer the patient to an endocrinologist for further workup. Pharmacists are also required to fully understand and interpret this test, as they will be involved in glycemic management medication agent selection, dosing, and monitoring. Both the nurse and/or pharmacist need to inform the treating physician regarding any changes in hemoglobin A1c and verify patient medication compliance. Hemoglobin A1c is a very valuable tool in the fight against diabetes and other glycemic control disorders, but to be effective, it functions best in an interprofessional healthcare team environment. [Level V]
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