The Hemoglobin A1c (HbA1c) Test for Diabetes
A1c testing is gaining support as the best standard of measuring blood sugar levels.
Glycosylated (or glycated) hemoglobin (hemoglobin A1c, Hb1c , HbA1c, or A1C; sometimes also HgA1c) is a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic pathway by hemoglobin's normal exposure to high plasma levels of glucose. Glycosylation of hemoglobin has been implicated in nephropathy and retinopathy in diabetes mellitus. Monitoring the HbA1c in type-1 diabetic patients may improve treatment.
Importance of Hemoglobin A1c Test
The hemoglobin A1c test -- also called HbA1c, glycated hemoglobin test, or glycohemoglobin -- is an important blood test used to determine how well your diabetes is being controlled. Hemoglobin A1c provides an average of your blood sugar control over a six to 12 week period and is used in conjunction with home blood sugar monitoring to make adjustments in your diabetes medicines.
Hemoglobin is a substance within red blood cells that carries oxygen throughout your body. When your diabetes is not controlled (meaning that your blood sugar is too high), sugar builds up in your blood and combines with your hemoglobin, becoming "glycated." Therefore, the average amount of sugar in your blood can be determined by measuring a hemoglobin A1c level. If your glucose levels have been high over recent weeks, your hemoglobin A1c test will be higher. The amount of hemoglobin A1c will reflect the last several weeks of blood sugar levels, typically encompassing a period of 120 days.
History of the A1c test
Hemoglobin A1c was first separated from other forms of hemoglobin by Huisman and Meyering in 1958 using a chromatographic column. It was first characterized as a glycoprotein by Bookchin and Gallop in 1968. Its increase in diabetes was first described in 1969 by Samuel Rahbar and coworkers. The reactions leading to its formation were characterized by Bunn and his co-workers in 1975. The use of hemoglobin A1c for monitoring the degree of control of glucose metabolism in diabetic patients was proposed in 1976 by Anthony Cerami, Ronald Koenig and coworkers.
In the normal 120-day life span of the red blood cell, glucose molecules react with hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, the quantities of these glycated hemoglobins are much higher than in healthy people.
Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell therefore reflects the average level of glucose to which the cell has been exposed during its life cycle. Measuring glycated hemoglobin assesses the effectiveness of therapy by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months. Some researchers state that the major proportion of its value is related to a rather shorter period of two to four weeks.
Laboratory results may differ depending on the analytical technique, the age of the subject, and biological variation among individuals. Two individuals with the same average blood sugar can have A1C values that differ by as much as 1 percentage point. In general, the reference range (that found in healthy persons), is about 4%–5.9%.
Higher levels of Hb A1c are found in people with persistently elevated blood sugar, as in diabetes mellitus. While diabetic patient treatment goals vary, many include a target range of Hb A1c values. A diabetic person with good glucose control has a Hb A1c level that is close to or within the reference range. The International Diabetes Federation and American College of Endocrinology recommend Hb A1c values below 6.5%, while American Diabetes Association recommends that the Hb A1c be below 7.0% for most patients. Recent results from large trials suggest that a target below 7% may be excessive: Below 7% the health benefits of reduced A1C become smaller, and the intensive glycemic control required to reach this level leads to an increased rate of dangerous hypoglycemic episodes.
Practitioners need to consider an individual patient's health, their risk of hypoglycemia, and their specific health risks when setting a target A1C level. For example, patients at high risk of microvascular complications may gain further benefits from reducing A1C below 7%. Because patients are responsible for averting or responding to their own hypoglycemic episodes, the patient's input and the doctor's assessment of the patient's self-care skills are also important.
A high HbA1c represents poor glucose control. However, a 'good' HbA1c in a patient with diabetes can still be riddled with a history of recent hypoglycemia, or, alternatively, spikes of hyperglycemia. Regular blood glucose monitoring is still the best method for the analysis of overall vascular health with respect to blood sugar control. Often, patients with diabetes mellitus are scolded by their doctors for having a HbA1c which is too low, because a lower A1c would indicate a likelihood of frequent hypoglycemia in the recent past. This is often assessed with blood sugar data and receptions are typically mixed. A balance of long term health (hyperglycemia prevention) versus short term health (hypoglycemia prevention) is always a constant concern for both patients and their doctors. Doctors are especially sensitive about lower level HbA1c's with patients who regularly drive, this being a prime example of a short-term motivation for preventing hypoglycemia. Many diabetics have died behind the wheel as a result of a low blood sugar, especially for the reason that frequent hypoglycemia results in a higher tolerance (ideally the patient is seized with a feeling of panic, an increased heart rate, profuse sweating, etc.) for the condition and some patients may not even consciously realize their blood sugar has dropped to dangerous levels. In addition to acquired tolerance, the use of alcohol and certain drugs (marijuana, for example) can create moderately similar symptoms to those of hypoglycemia (especially when used in combination) and for this reason the patient may not realize he/she has contracted hypoglycemia.
Persistent elevations in blood sugar (and therefore HbA1c) increase the risk for the long-term vascular complications of diabetes such as coronary disease, heart attack, stroke, heart failure, kidney failure, blindness, erectile dysfunction, neuropathy (loss of sensation, especially in the feet), gangrene, and gastroparesis (slowed emptying of the stomach). Poor blood glucose control also increases the risk of short-term complications of surgery such as poor wound healing.
Lower than expected levels of HbA1c can be seen in people with shortened red blood cell life span, such as with glucose-6-phosphate dehydrogenase deficiency, sickle-cell disease, or any other condition causing premature red blood cell death. Conversely, higher than expected levels can be seen in people with a longer red blood cell life span, such as with Vitamin B12 or folate deficiency.
The approximate mapping between HbA1c values and average blood glucose measurements over the previous 4–12 weeks is shown in the
Normal Hemoglobin A1c Test
For people without diabetes, the normal range for the hemoglobin A1c test is between 4% and 6%. Because studies have repeatedly shown that out-of-control diabetes results in complications from the disease, the goal for people with diabetes is an hemoglobin A1c less than 7%. The higher the hemoglobin A1c, the higher the risks of developing complications related to diabetes.
People with diabetes should have this test every three months to determine whether their blood sugars have reached the target level of control. Those who have their diabetes under good control may be able to wait longer between the blood tests, but experts recommend checking at least 2 times a year.
Patients with diseases affecting hemoglobin such as anemia may get abnormal results with this test. Other abnormalities that can affect the results of the hemoglobin A1c include supplements such as vitamins C and E and high cholesterol levels. Kidney disease and liver disease may also affect the result of the hemoglobin A1c test.
How it's used
The A1c test and eAG calculation are used primarily to monitor the glucose control of diabetics over time. The goal of those with diabetes is to keep their blood glucose levels as close to normal as possible. This helps to minimize the complications caused by chronically elevated glucose levels, such as progressive damage to body organs like the kidneys, eyes, cardiovascular system, and nerves. The A1c test and eAG result give a picture of the average amount of glucose in the blood over the last few months. They can help you and your doctor know if the measures you are taking to control your diabetes are successful or need to be adjusted.
The A1c test is frequently used to help newly diagnosed diabetics determine how elevated their uncontrolled blood glucose levels have been. It may be ordered several times while control is being achieved, and then several times a year to verify that good control is being maintained.
When the test should be used
Depending on the type of diabetes that you have, how well your diabetes is controlled, and your doctor, your A1c may be measured 2 to 4 times each year. The American Diabetes Association recommends testing your A1c at least twice a year. When someone is first diagnosed with diabetes or if control is not good, A1c may be ordered more frequently.
What the test means
A1c is currently reported as a percentage, and it is recommended that diabetics aim to keep their A1c below 7%. The report for your A1c test also may include an estimated Average Glucose (eAG), which is a calculated result based on your A1c levels. The purpose of reporting eAG is to help you relate your A1c results to your everyday glucose monitoring levels. The formula for eAG converts percentage A1c to units of mg/dL or mmol/L so that you can compare it to your glucose levels from home monitoring systems or laboratory tests.
It should be noted that the eAG is still an evaluation of your glucose over the last couple of months. It will not match up exactly to any one daily glucose test result. The American Diabetes Association has adopted this calculation and provides a calculator and information on the eAG on their web site.
A nondiabetic person will have an A1c between 4% and 6%. The closer a diabetic can keep their A1c to 6% without experiencing excessive hypoglycemia, the better their diabetes is in control. As the A1c and eAG increase, so does the risk of complications.
The A1c test will not reflect temporary, acute blood glucose increases or decreases. The glucose swings of someone who has “brittle” diabetes will not be reflected in the A1c.
If you have a hemoglobin variant, such as sickle cell hemoglobin (hemoglobin S), you will have a decreased amount of hemoglobin A. This may limit the usefulness of the A1c test in monitoring your diabetes. If you have anemia, hemolysis, or heavy bleeding, your test results may be falsely low. If you are iron deficient, you may have an increased A1c measurement. If you have had a recent transfusion, then your A1c will be falsely increased (blood preservative solutions contain high glucose levels) and not accurately reflect your glucose control for 2 to 3 months.
Everyone with diabetes is familiar with the standard, fasting blood-glucose test that is used to indicate your current blood sugar levels. The fasting test is the warhorse of diabetes management, and it helps you and your doctor see how your treatment is going.
But while the fasting test remains an important part of diabetes treatment, its weakness is that it is an indication of your glucose level only at the moment you take the test. A fasting blood sugar doesn't tell you anything about your blood-sugar levels the rest of the time.
The hemoglobin A1c test -- usually called the A1c -- fills this gap by testing your blood sugar in a different way. As your body processes blood sugar, small amounts of glucose naturally bond with hemoglobin, a protein in the red blood cells. What's significant is that the amount of glucose that combines with the hemoglobin is directly proportional to the total amount of glucose that is currently in your system.
As a result, the hemoglobin bonded with glucose (glycated hemoglobin, or A1c) can be used as an overall record of glucose levels for as long as the individual red blood cell lives, which is about two to three months. While a fasting test gives you an indication only of current glucose levels, the A1c gives you the big picture of what your average levels are over this whole two to three month period.
The Benefits of the A1c test
Getting a reading of overall blood glucose, instead of relying only on a series of fasting readings, has made a big difference in diabetes management.
Goldstein says that fasting-glucose tests alone were not a very good indicator of how well a person was doing in controlling his or her blood sugars. He says that he and other experts used to be surprised by patients who appeared to have good glycemic control -- based on fasting sugars -- but who would then suddenly develop serious complications.
"By checking the A1c, we don't see surprises like that anymore," Goldstein tells WebMD. "When we monitor people in the long term, we don't see people with great A1c levels developing classic complications of diabetes."
The test itself is simple and quick and thanks to the work of the NGSP (formerly the National Glycohemoglobin Standardization Program), more than 90% of all A1c tests are now standardized, meaning that the results from different labs should be comparable. Experts are not yet sure how often people with diabetes need to have their A1c tested, but the American Diabetes Association settled on a range of two to four times per year based on current evidence.
Target A1c numbers
Experts agree that a normal A1c for someone without diabetes is between 4%-6%; anything above that should be considered a sign of diabetes.
But exactly where you should be on that scale is debated and the recommendations for target A1c levels vary. For instance, the American Diabetes Association recently changed its recommended A1c from under 8% to 7% or below. Meanwhile, the American Association of Clinical Endocrinologists (AACE) recommends an even lower number of less than 6.5%.
All of these different numbers might leave you a bit confused. However, the general rule is that the closer to a normal A1c a person can get, the better, provided that the glucose control is not so strict -- or tight, in medical terminology -- that it induces hypoglycemia, a level of blood sugar that is too low. Treatment almost always includes behavioral techniques, such as weight loss and exercise, and may include medications to lower blood sugar levels.
But it's important to know that not everyone can reach these goals. "I've been delighted with the number of patients I have with A1c levels in the low 6% area," says Paul Jellinger, MD, past president of the American Association of Endocrinologists. "But in some patients who have unstable blood sugar levels, you're content with 7.2% or 7.4%, since that's the best you can do."
Goldstein is somewhat doubtful of the new, lower targets. "I agree that people should strive for the lowest A1c possible," he says, "but most patients can't achieve either the ADA or the AACE goals with current therapies because they're so low. And I think that you have to be careful not to set a goal that most people can't attain."
So what's the upshot? Get your A1c tested regularly and consult with your doctor about what target you should set. In general, aim for below 6.5% or 7%, but understand that it may not always be possible to get there.
At least one at-home test kit for A1c levels has been developed, and more are probably on the way. While it may be somewhat more convenient than trudging into the doctor's office, Goldstein and Kaufman are a little skeptical of their usefulness.
"If A1c levels were something that you had to monitor every few days, a home test would make more sense," says Goldstein. "But A1c is a long-term measure of blood sugars and you don't need to do it very often, maybe every few months. So why do people need to do it at home and why would doctors want them to?"
"I'm concerned about people doing these at home," Kaufman tells WebMD. "I don't want people to start doing A1c tests on their own and then thinking they can skip healthcare visits. It's not a substitute."
Instead, Kaufman and Goldstein recommend that A1c tests be administered in the doctor's office, where other indications -- such as blood pressure, cholesterol levels, and weight -- can also be checked. "People with diabetes need to be seeing their doctors regularly anyway," says Goldstein.
However, Goldstein does see at least one useful application of the home A1c test. "I think it might be good as a home-screening test, like a home pregnancy test," he says, "for people who haven't been diagnosed with diabetes but who are concerned about getting the disease."
Various health organizations have been stressing the importance of A1c in recent years. The U. S. Department of Health and Human Services partnered with the ADA to develop the "ABCs of Diabetes Program," encouraging regular monitoring of A1c, blood pressure, and cholesterol. More recently, the American Association of Diabetes Educators began the "Aim. Believe. Achieve. Diabetes A1c Initiative," a national educational campaign to raise awareness about the A1c test.
Given the importance of the A1c and the risks of diabetes, you must get your doctor to tell you what your A1c is and, if it's too high, what you can do to lower it. Experts stress the importance of aggressive management of diabetes, and you may have to push yourself and your doctor to achieve a better A1c level.
"There are still some doctors out there who don't understand what A1c targets should be or how to achieve them," says Kaufman. "If you've got a high A1c and your healthcare provider isn't helping you, it's time to get a consultation with somebody else."
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