When you received a diagnosis of diabetes, it likely was based on the results of one of three tests (or a combination of these tests): a fasting plasma glucose test, an oral glucose tolerance test, or a random plasma glucose reading. For many years, these have been the standard tests for assessing people with symptoms of diabetes and for screening people believed to be at risk of developing diabetes.
In 2010, the American Diabetes Association began recommending that another blood test, the glycosylated hemoglobin test — abbreviated either HbA1c or A1C — be used for diagnosing Type 1 or Type 2 diabetes. The A1C test has already proved its usefulness for monitoring the level of blood glucose control over time in people already diagnosed with diabetes. In its new, diagnostic, role, it is not intended to completely replace the older options, which still may be preferred in certain circumstances. But the A1C test is believed to have certain advantages over the older options, particularly when screening for Type 2 diabetes.
Changes over the years
This is not the first time in history that new methods of diagnosing diabetes have been developed or have become more widely accepted by the medical profession. Indeed, diabetes has been around a lot longer than any modern laboratory blood test.
The word “diabetes” is derived from a Greek word that means to siphon, pass through, or rapidly drain. (Accounts differ as to when it was coined; some say 200 BC, others during the second century AD.) But many centuries before the term was ever applied to the condition we now know as diabetes, a disease in which too much urine is eliminated was recognized. Somewhere along the line, it was noticed that this urine had a sweet smell and taste (and attracted insects and other animals), and for hundreds of years, the sweet taste of urine was the key to diagnosing diabetes.
The relationship between sweetness in the urine and sweetness in the blood was observed in 1776 by English physician Matthew Dobson. When Dobson evaporated the urine of people with diabetes, he found a substance that looked and tasted like brown sugar, and he also observed that people with diabetes had a sweetish taste to their blood. This led to the understanding of diabetes as not just a disease of the kidneys but as a system-wide disorder.
In the 1800’s, the first laboratory tests for glucose in the urine were developed, sparing physicians from having to taste it. The first tests simply identified that glucose was present in urine; later ones were able to measure the amount of glucose. A further advance, attributed to British physician Frederick Pavy, was to establish a quantitative relationship between the level of glucose in the blood with the level of glucose in the urine.
The 1900’s brought better ways to measure glucose in urine, as well as the first blood glucose tests.
As might be expected, the first blood glucose tests were not all that accurate, but over time, more and more accurate blood tests have been developed, leading to a greater understanding of the disease itself.
How today’s tests work
As mentioned earlier, the four tests currently used in the United States to diagnose diabetes are the fasting plasma glucose (FPG) test, the oral glucose tolerance test (OGTT), the random plasma glucose test, and the A1C test.
FPG. The FPG measures the concentration of glucose in the plasma (liquid) portion of the blood after a person has fasted for at least eight hours. Currently, a plasma glucose level over 126 milligrams per deciliter (mg/dl) is called diabetes, and, according to American Diabetes Association criteria, a level from 100 mg/dl to 125 mg/dl is called prediabetes.
OGTT. The OGTT involves two measurements of glucose in blood plasma: the first after a person has fasted for at least eight hours, the second two hours after the person has ingested 75 grams of glucose. A two-hour level of 200 mg/dl or higher is called diabetes, and a level from 140 mg/dl to 199 mg/dl is called prediabetes. (When the OGTT is used to detect gestational diabetes, or diabetes that occurs during pregnancy, different amounts of glucose and more frequent blood tests may be used, and the blood glucose levels at which diabetes is diagnosed are different, too.)
Random plasma glucose. This test measures blood glucose without regard to when a person last ate. A level of 200 mg/dl in a person who also has symptoms of diabetes can mean a person has diabetes. Generally, the diagnosis is confirmed with an FPG or an OGTT.
A1C. The A1C test measures the percentage of hemoglobin molecules in the blood that have glucose molecules attached to them. Currently, a test result of 6.5% or higher is diagnostic of diabetes.
From test to diagnosis
As early scientists no doubt discovered, everyone has some glucose in their blood. So how do you know whether a person has diabetes?
Just as methods of diagnosing diabetes have changed over the years, so have beliefs about what level of blood glucose should be called diabetes. In 1979, for example, the World Health Organization and the National Diabetes Data Group issued criteria for the diagnosis of diabetes stating that a fasting plasma glucose test result of 140 mg/dl or higher indicated diabetes. For the oral glucose tolerance test, a two-hour blood glucose level of 200 mg/dl or higher meant diabetes.
Almost 20 years later, in 1997, the American Diabetes Association updated these criteria, stating that a fasting plasma glucose test result of 126 mg/dl or higher indicated diabetes. But they retained the diagnostic level of a two-hour reading of 200 mg/dl or higher for the oral glucose tolerance test (for people who are not pregnant).
Why the change? High blood glucose may or may not cause symptoms, depending on how high it is and how accustomed a person has become to living with elevated blood glucose. (This is why people with Type 2 diabetes often have the condition for many years before they are diagnosed.) But whether or not high blood glucose is causing noticeable symptoms, it is potentially damaging a variety of bodily systems and setting the stage for long-term diabetes complications. The change from 140 mg/dl to 126 mg/dl when using the fasting plasma glucose test was largely based on studies showing that the number of cases of retinopathy (a form of diabetes-related damage to the eye) increased at fasting plasma glucose levels of 126 mg/dl and higher.
As researchers continue to conduct studies in which they measure participants’ blood glucose levels and whether and when these people develop diabetes-related complications, it’s possible the diagnostic cut point will change again.
In 2002, the term “prediabetes” became more widely used to describe blood glucose levels that are higher than normal but not high enough for a diagnosis of diabetes. Many people with prediabetes go on to develop Type 2 diabetes, but it is possible to take preventive action. There is evidence that increasing physical activity and improving eating habits can delay or prevent the onset of Type 2 diabetes in those with prediabetes.
Using the A1C for diagnosis
Among the benefits of using the A1C test to diagnose diabetes or prediabetes is that a blood sample for the test can be obtained at any time. It is not necessary to fast before having the test done, nor does the test re-quire drinking a glucose solution as part of the test. In addition, A1C level is unaffected by stress or illness at the time of the blood draw.
The A1C test may be less useful for diagnosing Type 1 diabetes than Type 2 because people with Type 1 diabetes often have acute symptoms and very high blood glucose levels when they are diagnosed. A random plasma glucose test, which also doesn’t require fasting or drinking glucose, can easily pick this up.
The A1C test is not recommended for diagnosing gestational diabetes, because a woman with gestational diabetes would likely not have an elevated A1C, even when her OGTT result is diagnostic of diabetes. This is because the A1C test gives an estimate of average blood glucose level over the past two to three months, and the OGTT is done when a woman would typically start having high blood glucose during pregnancy, not three months after she might start having high blood glucose. Waiting for her A1C to rise would delay necessary treatment.
The A1C test is also not recommended for diagnosing previously undiagnosed Type 1 or Type 2 diabetes during pregnancy, because changes in the rate of red blood cell turnover that occur during pregnancy would make the test inaccurate.
There are also some medical conditions affecting the blood that make A1C testing inaccurate. For people who have these conditions, either the FPG or the OGTT must be used for diagnosis (and different tests must be used for evaluating long-term blood glucose control).
When the A1C test is used to test for diabetes, the ADA’s International Expert Committee has proposed 6.5% as the level at which diabetes is diagnosed. (Diagnosis should be confirmed with a repeat A1C test unless symptoms of diabetes and blood glucose levels over 200 mg/dl are present.) The committee has also proposed the range of 6% to 6.5% as the level of highest risk for progression to diabetes, indicating that preventive measures might be in order. However, when a person has known risk factors for diabetes, an A1C level lower than 6% might also call for preventive measures.
These recommended cutoffs are based on research showing the usual range of A1C levels found among people who do not have diabetes, those with prediabetes, and those with diabetes. However, researchers have already raised concerns that these cutoffs underdiagnose diabetes in the elderly population as well as in certain ethnic and minority groups. The cutoffs may also not be right for diagnosing diabetes in nonwestern countries. Also, in some countries, the higher cost of A1C testing and/or the lack of standardization among laboratories may make the A1C test less useful as a screening tool.
Research will no doubt continue as use of the A1C test for diagnostic purposes becomes more widespread, and more will be learned about how best to use it in different populations.
Refining the diagnosis
The vast majority of cases of diabetes are either Type 1 diabetes, Type 2 diabetes, or gestational diabetes. All are diagnosed on the basis of high blood glucose, but none of the tests used for diagnosis discriminates between types of diabetes. For that, physicians use other criteria, such as symptoms, whether a woman is pregnant, and personal characteristics such as age, body-mass index, family history, and the presence of certain other health conditions.
In many if not most cases, that’s enough to make a correct diagnosis. But sometimes it’s not clear what type of diabetes a person has. In those cases, a health-care provider may order further tests, since a misdiagnosis can lead to suboptimal treatment.
One type of testing that may be done is autoantibody testing. When Type 1 diabetes or latent autoimmune diabetes in adults (LADA) is suspected, a blood test that screens for autoantibodies to islet cells, insulin, and glutamic acid decarboxylase (and possibly some others) may be done. The presence of such autoantibodies indicates that the body is engaged in a destructive immune response against its insulin-producing cells.
Another test that may be done if a doctor suspects Type 1 diabetes or LADA is a C-peptide test. C-peptide is a by-product of insulin formation in the pancreas. The pancreas first creates proinsulin, a large protein that breaks down into three chains of amino acids, two of which recombine to become insulin, and one of which, known as C-peptide, is secreted into the bloodstream along with insulin. While the function of C-peptide is currently not known, a person’s C-peptide level gives an indication of how much insulin his pancreas is producing.
Infants who develop diabetes within the first six months of life may undergo genetic testing to see whether they have a rare form of diabetes called neonatal diabetes, which occurs because of a genetic defect. Neonatal diabetes may be mistaken for Type 1 diabetes, but infants who have it may do better when treated with sulfonylureas (a type of oral drug) than with insulin.
Another type of diabetes that is caused by a genetic defect is Maturity Onset Diabetes of Youth (MODY). In fact, there are several varieties of MODY, each caused by a different gene abnormality. Some forms of MODY can be treated well with pills, while others require insulin therapy. Because genetic testing for MODY is expensive, it is not done frequently. However, if a parent has a form of MODY, his children have a 50% chance of also having it. Detecting it early in children allows for early treatment and possibly prevention of long-term complications.
When to screen
Currently, the ADA recommends testing for diabetes when a person has symptoms of diabetes such as frequently passing large volumes of urine, excessive thirst, weight loss, and sometimes increased hunger and blurred vision.
The ADA states that health-care providers should consider screening for Type 2 diabetes in adults of any age who are overweight or obese and who have one or more additional risk factors for Type 2 diabetes. Those risk factors include the following:
- Physical inactivity
- Having a first-degree relative with diabetes
- Being a member of an ethnic population with a high prevalence of diabetes (African-American, Latino, Native American, Asian American, Pacific Islander)
- Having delivered a baby weighing more than 9 pounds or having been diagnosed with gestational diabetes
- Having high blood pressure (equal to or higher than 140/90 mm Hg) or being treated for high blood pressure
- Having an HDL cholesterol level lower than 35 mg/dl and/or a triglyceride level higher than 250 mg/dl
- Having polycystic ovary syndrome
- Having an A1C equal to or greater than 5.7% or having been diagnosed with impaired glucose tolerance or impaired fasting glucose on a previous occasion
- Having other conditions associated with insulin resistance such as severe obesity or acanthosis nigricans (a darkening of the skin that commonly occurs in the folds of the armpits, neck, or groin)
- Having a history of cardiovascular disease
In adults without these risk factors, the ADA states that diabetes screening should begin at age 45. If tests do not show elevated blood glucose, testing should be repeated at least every three years.
However, at least one recent study concludes that it is cost-effective to screen US adults for Type 2 diabetes between the ages of 30 and 45. So it’s possible the criteria for screening for Type 2 diabetes may change some day, too.
News you can use?
The news that the A1C test will now be used to diagnose diabetes in the United States will likely have no great impact on people already diagnosed with diabetes. However, because Type 2 diabetes is known to have a genetic component — meaning that the risk of developing Type 2 diabetes is higher if your close relatives have it — this new use of the A1C test is something you may want to share with your family members. If they’ve been putting off getting screened for diabetes because of the inconvenience of fasting for eight hours before having blood drawn, now there’s no more reason to delay. And if they’re still not convinced to get screened, direct your relatives to the Web page www.diabetes.org/risk-test.jsp. This online tool can tell an individual whether he is at low, moderate, or high risk of having prediabetes or Type 2 diabetes.
If your family members have a little more time (about 15 minutes), the ADA’s “My Health Advisor” tool, found at http://myhealthadvisor.diabetes.org/cmrm/index.jsp, can calculate a person’s risk of developing Type 2 diabetes, heart attack, or stroke. It can additionally show how much a person’s risk of these conditions can be changed by making certain lifestyle changes.
There’s never a good time to be diagnosed with diabetes, but if you have it — or you have prediabetes — the best time to know about it is as soon as possible. Once you know, you can start taking steps to prevent prediabetes from becoming Type 2 diabetes or to prevent long-term diabetes complications if you already have Type 2 diabetes. Encourage your friends and family members to take advantage of today’s modern laboratory tests and to get screened for Type 2 diabetes if they have any risk factors.