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H-B-A-1-C
(What It Is and Why It Matters)

by Mark Nakamoto

What’s in a name? If you look through both the scientific literature and the information produced specifically for people who have diabetes, you will probably see a variety of terms to describe the HbA1c test, such as glycosylated hemoglobin, glycated hemoglobin, and glycohemoglobin, and abbreviations such as GHb and A1C. For the purposes of the average person with diabetes and his health-care team, these terms are all basically referring to the same thing.

When a molecule is said to be glycosylated, it means it has been linked to a glycosyl group (a derivative of a glucose molecule). Glycosylation can either be aided by helper molecules called enzymes or occur chemically without the enzymes. The nonenzymatic form of glycosylation is called glycation. When being precise in their writings for scientific journals, biochemists tend to call the form of hemoglobin examined in the HbA1c test a “glycated hemoglobin,” because the process by which glucose links itself to hemoglobin is nonenzymatic. “Glyco-” is a prefix that usually refers to a sugar, so a glycohemoglobin is a hemoglobin with some sort of sugar attached. GHb is used as a catch-all shorthand for glycosylated and glycated hemoglobin and glycohemoglobin.

To reduce the confusion that all these different-sounding terms could cause, in August 2001, the American Association of Clinical Endocrinologists and the American College of Endocrinology recommended that health-care providers use the shorthand term “A1C” when speaking with people with diabetes, a change that the American Diabetes Association (ADA), the National Glycohemoglobin Standardization Program (NGSP), and the National Diabetes Education Program (NDEP) came to endorse. Researchers were encouraged to continue to use the term “glycated hemoglobin” in scientific papers aimed at their peers.

Setting a standard
In the past, a physician’s previous personal experience with a certain illness or the opinion solicited from a specialist at the local medical center used to be considered the basis for good medical care. Over the years, however, physicians came to desire more research-based, statistical data to support long-standing medical practices and to ensure that people were given the best medical care possible. The tail end of the 20th century saw the increasing use of controlled clinical trials to compare the effectiveness and safety of various drugs and therapies. To test theories on whether high blood glucose levels were responsible for some of the complications of diabetes and if complications could be reduced or reversed by lowering blood glucose levels, a number of trials involving volunteers with diabetes were conducted.

Type 1 diabetes. The longest and largest well-conducted study of controlling high blood glucose in people with Type 1 diabetes was the Diabetes Control and Complications Trial (DCCT). Between 1983 and 1993, the DCCT enrolled and studied over 1400 people with Type 1 diabetes, assigning them to receive either a conventional therapy (one or two daily injections of insulin and either urine testing for glucose several times per day or blood glucose monitoring once per day) or a more intensive regimen intended to achieve near-normal levels of blood glucose. The intensive regimen consisted of monitoring blood glucose levels four times daily and either the use of an insulin pump or three or four daily injections of insulin. The HbA1c test was used to assess the level of blood glucose control achieved by each group and to compare the groups. After an average of 6.5 years of follow-up, people in the intensive-treatment group attained an average HbA1c of 7.3%, while the average HbA1c in the conventional-therapy group was 9.1%.

These differences in HbA1c results translated into significant differences in risks for diabetes complications such as nephropathy (kidney disease), retinopathy (eye disease), and neuropathy (damage to and malfunctioning of nerves, especially those of the legs and feet). When the kidneys are functioning normally, they do not allow proteins from the blood to be filtered out in the urine. Kidneys damaged by diseases such diabetic nephropathy can allow a blood protein called albumin to pass into the urine. Intensive control of blood glucose reduced the development of macroalbuminuria (large amounts of albumin in the urine) by 56%. Every 10% decrease in HbA1c (say, from 11% to 9.9%) led to a 25% decrease in risk for developing signs of nephropathy.

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