Diabetes Forecast May 2005

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FOR TYPE 1/TYPE 2

Research Profile

You Say Tomato…
Same Blood Glucose, Different A1Cs
by Terri Kordella

Stuart A. Chalew, MD, with colleague and co-investigator James M. Hempe, PhD, is studying how glucose attaches to hemoglobin in red blood cells. He wants to learn why two people with the same average blood glucose can have different A1C measurements.	Stuart A. Chalew, MD Occupation Director of Pediatric Endocrinology, Professor of Pediatrics, Louisiana State University Health Sciences Center and Children's Hospital Professional Focus Pediatric endocrinology and diabetes Outside Interests Listening to classical music Research Funding ADA Clinical Research Award

When you have diabetes, you have to take a lot of blood tests.

There are your daily, routine blood glucose checks, when you get out your meter and check your levels in real time. Then there are A1C tests, which provide a snapshot of blood glucose control over 3 months.

Blood glucose measurements are pretty simple: They tell you how many milligrams of glucose are in each deciliter of your blood. But the A1C is a little bit more complex: It reveals the percentage of hemoglobin within your red blood cells with glucose attached.

Hemoglobin is the substance in your red blood cells that carries oxygen from your lungs to different parts of your body. It's also what makes your red blood cells red. Glucose may become attached to hemoglobin through a complex process called glycation. (Sometimes your doctor may refer to the A1C as glycated hemoglobin or HbA1C. The Hb is for "hemoglobin," and the A1C designates a specific kind of hemoglobin.) The higher your average daily blood glucose, the more glucose will attach to your hemoglobin, and the higher your A1C measurement will be.

There's just one catch, says Stuart A. Chalew, MD, director of pediatric endocrinology and professor of pediatrics at the Louisiana State University Health Sciences Center and Children's Hospital in New Orleans. According to Chalew, it's possible for different people with the same average blood glucose to have different A1C levels.

For instance, someone whose average blood glucose is 175 mg/dl typically will have a higher A1C than someone whose average blood glucose is 100 mg/dl. But two people who have an average blood glucose of 175 mg/dl may have different A1Cs.

"Some people have higher or lower A1Cs despite exposure to the same amount of blood glucose," Chalew says. "The glycation process appears to be individualized."

Chalew is using funds from an American Diabetes Association Clinical Research Award to study this phenomenon.

High Glycators, Low Glycators

To delve into the mysteries of glycation, Chalew and his team will look at the blood glucose and A1C measurements of roughly 500 children with type 1, with an average age of 12 years. They will compare the children's average blood glucose measurements to their A1C measurements and divide the children into four or five groups according to how high their A1Cs are in relation to their average blood glucose. Those with the highest A1Cs in relation to their blood glucose—the "high glycators"—will be at one end of the spectrum, while those whose A1Cs are the lowest in relation to their blood glucose—the "low glycators"—will be at the other.

Much of the research will focus on how glycation occurs in the high glycators and the low glycators. How does it differ between those two groups? Is there anything special in the process among either the high glycators or the low glycators that sets them apart from each other?

The answers may lie in the blood. At a lab run by Chalew's co-investigator James M. Hempe, PhD, at the Children's Hospital Research Institute, the team will study blood samples drawn from the children every 3 or 4 months during routine diabetes care visits at the clinic. The team will measure how much glucose is surrounding the red blood cells and how much of the hemoglobin has glucose attached. Then they will "wash" the glucose out of the blood and out of the red blood cells and expose the blood to new glucose. This will enable them to observe exactly how the glucose gets into the red blood cells to attach to the hemoglobin.

"Hemoglobin glycation is a chemical process that occurs slowly," says Chalew. "The glucose gets into the red blood cells, but not through insulin, like in other cells. Once it's there, it can be metabolized [used for energy], or it can attach to hemoglobin."

The team's job, then, is to see exactly how much glucose gets into the cells, how it is metabolized, and how much it attaches to the hemoglobin. They will also look at how metabolism in the cells determines glycation. Then they will compare what they observed in each group of children and note the differences.

"There could be an additional component that could be manipulated, something that helps regulate metabolism in the red blood cells. Once it's identified, therapies could be designed to affect or control that component," Chalew says.

Such a therapy could mean a lower risk for diabetes-related complications. Several studies have revealed that, daily blood glucose readings aside, the higher your A1C, the more likely you are to develop diabetes-related complications. (The American Diabetes Association recommends that you aim for an A1C of 7 percent or lower.)

"Blood glucose is a powerful determinant of what your A1C is, but we may be able to get an even better, more sophisticated prediction of A1C if we know whether a person is a high glycator or low glycator" Chalew says. "Even if your blood glucose is okay, if you are a high glycator, you would want to get the A1C down because of the risk for complications. The trick is finding out how to help high glycators lower their A1Cs."