Ten years ago, you probably hadn’t heard of the glycohemoglobin test. Today, it seems everybody’s talking about it. (You’ve probably heard of the most common one—the HbA1C.)

A glycohemoglobin (GHb) test tells you what your average blood glucose level was over the past 4 months, yet it requires only a single drop of blood, collected at any time of day. GHb testing is being used routinely all around the world to help people with insulin-dependent (type I) diabetes and non-insulin-dependent (type II) diabetes manage their disease. The test has also played an important role in many diabetes research projects, including the recently completed Diabetes Control and Complications Trial (DCCT).

Despite all the talk about GHb, many people don’t clearly understand what the GHb test is and what it does. Do you know the answers to the most commonly asked questions about the GHb test? Let’s find out.

What is glycohemoglobin?

Hemoglobin is a protein molecule inside red blood cells that carries oxygen from the lungs to all the cells and tissues of the body. Like all other proteins, hemoglobin can link up with sugars, such as glucose. Glucose in your bloodstream is constantly entering your red blood cells and linking up with, or glycosylating (glycating means the same thing) hemoglobin.

Once the hemoglobin gets glycosylated, it stays glycosylated. If your blood glucose was high last week, then more of your hemoglobin was glycosylated than usual. This week, your blood glucose might be back under control again, but your red blood cells will still be carrying the "memory" of last week’s high blood glucose level. That memory will not be erased completely until the last of the red blood cells now in your blood have died and been replaced by fresh cells which contain fresh hemoglobin. That takes about 4 months.

The more glucose there is in the blood, the more hemoglobin will become glycosylated. About 5 percent of the hemoglobin of a person who doesn’t have diabetes is glycosylated. In a person with diabetes, the level is typically higher because of the higher blood glucose levels.

How much higher depends on what the person’s average blood glucose level has been. For example, if average blood glucose is 120 milligrams per deciliter (mg/dl), the GHb is about 6 percent. An average blood glucose level of 330 will produce a GHb of about 13 percent. (See insert)

Is GHb the same thing as hemoglobin A1C (pronounced A-one-C)?

All hemoglobin-glucose linkages are considered to be glycohemoglobins or GHbs. Hemoglobin A1C (also written HbA1C) is a very specific GHb in which the hemoglobin-glucose linkage takes place at only one place on the hemoglobin molecule. Some GHb test methods measure only hemoglobin A1C while others measure all GHbs together. Other terms you may encounter include hemoglobin A1, total glycated hemoglobin, or total GHb. Again, these are just different forms of GHb.

It doesn’t matter which form of GHb is measured. Each can provide the same useful information about your average blood glucose levels. What complicates things is that different GHb tests give different numbers. A "7 percent" on one test is the same as a "9 percent" using another test, even though both indicate the same average blood glucose level.

This problem will be solved only when all test numbers are reported on the same scale. The American Diabetes Association and many Canadian organisations are working hard to develop standards so that the results from one laboratory will be directly comparable to results from another. For now, it is very important that your doctor knows how to translate your GHb result into your average blood glucose level.

How long is the blood glucose memory of this test?

Some articles say 4 months, others say 2 to 3 months, and still others say weeks-to-months. Can’t the experts agree?

The GHb level is not a simple average of all the blood glucose level ups-and-downs over the past 4 months. It is a "weighted average."

An individual red blood cell lives 120 days—about 4 months. But you don’t get a complete turnover of red blood cells once every 4 months. Old ones are constantly dying, and new ones are constantly being produced. At any one time, some of your red blood cells will be old, some middle-aged, and some young.

The GHb result is affected more by recent blood glucose levels than by older ones. Blood glucose levels from 3 to 4 months ago contribute only about 10 percent to the result. That’s because most of the red blood cells that were around then have died off. Your blood glucose levels over the past month count more—they contribute about one-half to the result. That’s what is meant by a weighted average.

Because of this, GHb results can be a bit misleading at times. For example, let’s say your blood glucose levels were near-normal during January, February, and March, but were high during April. Your GHb level will indicate a higher average blood glucose level than what it really was over the entire previous 4 months, because April counted more in the GHb result than did January.

The other side of the coin is that if your blood glucose levels had been well controlled the past month but high for several months before, the GHb level would indicate a somewhat lower average blood glucose than what it actually had been.

Your best protection against being misled by a GHb result is to have your GHb level checked at regular intervals.



Average Blood
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How often should I have my GHb level measured?

The ADA recommends that the GHb level first be measured at the time of diagnosis and initiation of treatment. Thereafter, the test should be done at least twice a year in people with non-insulin-dependent (type II) diabetes who don’t use insulin; four times a year in people with insulin-dependent (type I) diabetes or those with type II diabetes who use insulin. It should be done more frequently in people with either type I or type II diabetes whose blood glucose levels are not well controlled.

These are just guidelines. The actual frequency of testing should be decided by you and your health-care team.

I am not sure if my doctor has been ordering the GHb test on me. How do I find out?

Finally, an easy answer! Just ask your doctor. If necessary, give your doctor a copy of this article.

If my blood glucose control improves quite a bit, how long does it take to see it in my GHb test?

As we discussed above, it takes about 4 months to see all the effects of a change in blood glucose levels. But you don’t need to wait 4 months to see a meaningful change in your GHb level after your blood glucose control changes. Depending on how great the change is (up or down), your GHb test can show quite a big change after only one to two weeks. On the practical side, it’s probably not very useful to check a GHb level more than once a month.

My friend and I both have diabetes but we go to different doctors. My friend said her last GHb was 10

percent and her doctor was very pleased. My doctor gets pretty upset when my level is over 9 percent. What gives?

Remember that GHb tests done in different laboratories may give different numbers that mean the same thing when they are translated into the average blood glucose level. It’s likely that your friend’s doctor does not use the same laboratory to measure the GHb test as your doctor does. One other possibility is that your friend has had a much more difficult time controlling her blood glucose levels than you, and the test result was quite an improvement over the time before. Each person should work with his or her health-care team to set GHb goals.

If the GHb test can tell my average blood glucose level for months at a time, why do I need to do blood glucose tests every day?

A GHb level is akin to a baseball player’s season batting average. The batting average provides useful information about overall batting success. But the season batting average can’t help much with batting success in a single game.

The blood glucose tests you do yourself measure the level of glucose in your blood at the time of the test. These are very important for the day-to-day management of your diabetes. They may prompt you to eat a snack, take more insulin, or exercise more or less. The steps you take because of your daily blood glucose results will be reflected in your next GHb.

OK, if I’m doing at-home tests every day, why do I need a GHb test?

Because you can’t do enough tests every day to get the full picture. The GHb test gives you the full picture.

Let’s say you have type II diabetes and you test your blood glucose once a day, before breakfast. The level is usually around 120 mg/dl. But your last GHb test tells you that your average blood glucose is more like 250. That’s worth knowing.

You’ll rarely get the pleasant surprise of a low GHb. If you get a surprise, it will almost always be a high GHb. That will come from "hidden" high blood glucose levels—the times when your blood glucose was high, but you didn’t know because you didn’t test your blood then.

You need to figure out why there is this difference between your daily recorded value and your GHb result. Your health-care team will probably advise you to test your blood more often for a few weeks, or to test at different times.

Doing this, you may discover, for example, that your after-dinner blood glucose level is often higher than 200. There’s your answer. You can discuss these results with your health-care team and make the appropriate changes in your diabetes regimen. You might alter your meal plan or try to increase your activity level. Changes in your treatment plan—increasing your oral medication dose or even starting insulin—might also be considered.

Here’s another example. Your son is 14 years old and has had type I diabetes since he was 5. He tests his blood glucose three or four times each day and the results are excellent—almost always between 70 and 140. But his last two GHb results were very high, indicating an average blood glucose level of about 300. Why?

This situation requires major detective work. Rarely, a medication that a person is taking interferes with the GHb result, and the reading is too high. Some people have unusual types of hemoglobin that fool the test. (Also, GHb results can be too low in people with certain anemias or recent blood loss.)

What’s most likely, however, is that your son’s home blood glucose tests results are not accurate. It’s possible that he’s doing his test readings incorrectly or that his glucose meter is defective.

It’s also possible that he records "better" values than what his meter shows, so that he won’t get a lecture from his doctor. That’s understandable, but it isn’t good for his health.

Whatever the reason, it’s very important to solve the mystery so your son and his health-care team can work to get the best blood glucose levels that are possible for him.

What did they learn about GHb in the Diabetes Control and Complications Trial?

The purpose of the DCCT was to determine if people who kept their blood glucose levels in the near-normal range developed fewer complications than people whose average blood glucose levels were higher (see Forecast, Sept. 1993, pp. 39–78). The DCCT results showed that there is a direct link between the glycohemoglobin levels and the risk of developing the complications. (The test used in the DCCT was the HbA1C.)

People who had GHb levels of about 7 percent had a much lower risk of developing complications of the eyes, kidneys, and nerves compared with people who had levels of about 9 percent. (On this scale, under 6.05 percent was the non-diabetic level.)

A high GHb is definitely a risk factor for diabetic complications.

What should my GHb test result be?

There is no easy answer to this question. It’s not possible to recommend that all people with diabetes aim for any specific GHb level. For one thing, GHb tests done in different laboratories may give different numbers, even from the same blood sample.

But more important, goals for GHb must be individualized. For example, people with type I diabetes are rarely able to achieve and maintain GHb levels in the nondiabetic range without experiencing frequent episodes of hypoglycemia (low blood glucose). On the other hand, many people with type II who are not on insulin can get near-normal glucose levels safely.

But remember that the DCCT showed that any improvement in GHb levels lowers your risk for developing complications. You may be able to improve your GHb levels. Discuss with your health-care team what your goal should be and how to reach it.

Wouldn’t GHb be a good test for diabetes screening and for diagnosis?

Maybe. The gold standard for diagnosis of diabetes is the oral glucose tolerance test (OGTT), even though it’s rarely necessary to perform the test to diagnose diabetes. Recent studies suggest that GHb may be useful to confirm, and perhaps to diagnose, diabetes. We predict that GHb will replace the OGTT as a diagnostic tool, but more studies are still needed. (We do know that GHb is not sensitive enough for diagnosing gestational diabetes.)

Your test is over. How’d you do? We confess that the test questions were very difficult, so don’t feel bad if you didn’t know all the answers. But now you do. So take the test with the memory and put it to work for you!

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