Interview: Dr. Zachary Bloomgarden on the HbA1c Assay

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During the normal 120-day life span of the red blood cell, glucose molecules react with hemoglobin forming glycated hemoglobin.  A few decades ago researchers discovered that 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 blood cell therefore reflects the average level of glucose to which the cell has been exposed during its 3 month life cycle. This is called HbA1c or gylcated hemoglobin and it is used by doctors (and patients) to monitor blood sugar control in diabetic patients.

Until this year, the HbA1c test was used only for monitoring patients once they had been diagnosed with diabetes. In January 2010, however, the  American Diabetes Association Standards of Medical Care in Diabetes added the measure of HbA1c  6.5% as a criterion for the diagnosis of diabetes, in addition to the fasting glucose test and the oral glucose tolerance test.

Dr. Zachary Bloomgarden, Clinical Professor in the Department of Medicine, Division of Endocrinology, Mount Sinai School of Medicine and one of the best-known diabetologists in New York, has written at length about the use of  HbA1c.  He took the time to answer some questions for us about the use of HbA1c as a diagnostic tool.

The HbA1c test has been around for decades, why is it being recommended as a diagnostic tool now?

What has changed is the continued and further standardization of the HbA1c assay. Analyses of the College of American Pathologists (CAP) surveys from 1993 to 2007 show much improvement in results. Furthermore, the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) has prepared new A1c standards to improve standardization.  Many people with diabetes (and many physicians and other healthcare providers taking care of diabetic patients) do not, however, realize that the current standard allows a HbA1c measurement to be within 8% – which means that a level of 6.5 could actually be a 6.0 or a 7.0.

What are the advantages of using HbA1c over glucose measurements?

There are several arguments in favor . One is that unless a specimen is taken to the lab right away (or the serum is separated from the plasma) then there is a drop in glucose levels from the time a sample is obtained to the time of processing, leading to inaccuracy. Furthermore, there is more variability week to week in fasting glucose levels than in HbA1c levels. Fasting glucose varies with the time of day, with acute stress and with many other factors, while HbA1c is a more integrated measurement of average glucose.  Also, it is already being used to guide treatment.

What are the disadvantages of using HbA1c to diagnose diabetes?

Because of the variability in glycation of hemoglobin there are some real practical issues.  People who have all sorts of medical illnesses, like kidney disease or infections will have abnormal red blood cell survival and will tend to have a lower HbA1c, interfering with the use of HbA1c in understanding their glucose exposure. It turns out that in a number of studies, African Americans have a higher level of HbA1c for a given level of blood sugar than do non-Hispanic whites. For example, a diabetic who has an HbA1c of 7.2% might be considered to have  worse blood sugar than  someone with a HbA1c of 6.8%, but if the first is African American and the second is non-Hispanic white, then they might actually have the exact same degree of blood sugar control.

Age is another factor that affects HbA1c. There are likely genetic differences from one person to another which have not yet been recognized but which cause one person to be a “high glycator” and another person to be a “low glycator.”

What are other medical factors that affect HbA1c?

Many medical conditions are associated with alterations in the relationship between mean glycemia and HbA1c.  The main conditions are those affecting red blood cells, such as persistent fetal hemoglobin, hemoglobin S, C, or D, advanced kidney disease, or illness characterized by hemolysis (the breaking up of red blood cells) or other states with shortened life span of red blood cells. There are a variety of systemic conditions including certain forms of dyslipidemia, malignancies,and cirrhosis. The common condition of iron deficiency anemia can, for unexplained reasons, lead to an increase in HbA1c by 1–1.5% that subsequently falls following iron treatment. Pregnancy is well recognized to be associated with a substantial reduction in HbA1c levels.

Given the frequency with which subjects with diabetes have other medical illnesses, the likelihood that such factors may alter HbA1C is widely underestimated.

Who would be diagnosed with diabetes, even if they didn’t have it?

It is reasonable to think that the use of HbA1c will lead to over-diagnosis among the elderly, blacks, people with iron deficiency, and individuals genetically predisposed to greater levels of hemoglobin glycation.

And who would not be diagnosed when they should be diagnosed?

Those with anemia, kidney disease, and many hemoglobinopathies, as well as those with other genetic variations, would be incorrectly told that they do not have diabetes.

Is this test available throughout the world?

A further entirely distinct argument against the use of HbA1c for diagnosis is the lack of access to this test in many of the countries where diabetes is likely to increase most in prevalence in the coming decades.

What about diagnosing prediabetes? Is it useful?

HbA1c has a low sensitivity for diagnosis of prediabetes.

Do you believe we are ready to embrace this change?

Given the fact that there is this heterogeneity, and that this has been shown in a number of studies, it is not apparent to me that the suggestion of the ADA that HbA1c be used in diagnosis  is something that we should rush to adopt.  A1c is very useful but not the same as glucose itself.

 

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Umesh

RBC lifespan is 120 days as also mentioned 1st in the article.

Then why is A1c test a 3 month average and not a 4 month average.

Can you clarify this?

Regards,

J Weber

I am a 53 years old WM, 5’11”, 175 lbs,eat right and have never had an elevated fasting or random serum glucose and yet my A1C is 6.2. I do have high cholesterol (235) which appear to be genetic, but no family history of CAD. What does the A1C mean to me? Should I be treated?

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i think this test is the way to go, at least as a guide anyway.  The test is not affected by too many other variables, with the glucose it can fluctuate through stress and other things too.

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