Home >> ALL ISSUES >> 2018 Issues >> Could CGM dethrone HbA1c for office-based diabetes care?

Could CGM dethrone HbA1c for office-based diabetes care?

image_pdfCreate PDF

Anne Paxton

December 2018—A glucose sensor the size of a quarter placed on the body and a sensor filament inserted under the skin could potentially disrupt traditional diabetes care with its continuous monitoring of glucose almost 300 times a day.

Blood glucose can fluctuate widely during the day even in completely healthy people, said David Sacks, MB, ChB, chief of clinical chemistry services in the Department of Laboratory Medicine, National Institutes of Health, in an interview with CAP TODAY. “With CGM, the patient can monitor glucose continuously over days by getting a reading every few minutes.”

The implications of CGM for HbA1c, long respected as a marker of the risk of complications from diabetes, are beginning to emerge, as studies show the devices can help patients avoid hypoglycemia and lower their average blood glucose concentrations. Endocrinologist Richard Bergenstal, MD, speaking in a session on refining measurement of HbA1c at this year’s AACC annual meeting, gave audience members and Dr. Sacks, the moderator, cause to wonder: “Is this the beginning of the end of HbA1c?”

Dr. Bergenstal

Dr. Bergenstal, executive director of the International Diabetes Center at Park Nicollet Institute in Minneapolis, is one of a growing number of experts who believe that single HbA1c results of a patient may be telling only part of the story. “In the clinic, A1c is missing a lot of the key elements we need for day-to-day management of diabetes,” Dr. Bergenstal said in his presentation, “What HbA1c Results Don’t Tell You.”

“Since 1993,” when the 10-year Diabetes Control and Complications Trial was completed, “we’ve really been living in an A1c era,” he said. “It’s a good population health measure. It’s a good accountability measure. We use it every day in the clinic where I live.” But “Is the A1c the be all and end all, end of story?” He doesn’t think so. The goal of his talk, he told the audience, was “to move you past A1c into the world of CGM.”

HbA1c is used to diagnose diabetes, to evaluate how effective therapy is, and, probably most important, to predict the risk of irreversible complications, Dr. Sacks notes. “If a patient just sticks a finger, that only tells the glucose at the second when the blood was drawn, and that varies a lot at different times of the day.” HbA1c, on the other hand, reflects the average glucose over the preceding two to three months. “That’s because glucose goes into the red cells, binds the hemoglobin, and the glucose molecule gets irreversibly stuck onto the hemoglobin forming this molecule called HbA1c.”

The current guidelines for almost all clinical organizations are that individuals with type 1 or 2 diabetes have their HbA1c measured at least twice a year and more often if there is a change in therapy or if the patient is not meeting therapeutic goals, Dr. Sacks says.

But HbA1c is imperfect because factors other than glucose can alter it. Analytic factors make up one group; they can interfere with measurement and usually can be addressed by use of a different method. “The second group of factors are more of an issue. They are things that change the HbA1c and have nothing to do with glucose,” he notes. Race is one factor because there is convincing evidence that African Americans have higher HbA1c than Caucasians. Other factors include iron deficiency or chronic kidney disease. “Are the changes these factors make in HbA1c clinically meaningful? There are studies ongoing to resolve this question. It’s become a very important topic that people weren’t aware of 20 years ago,” Dr. Sacks says.

Clinicians in many countries are increasingly using CGM to estimate HbA1c in addition to measuring it in the laboratory, he says. He compares this to estimating glomerular filtration rate in addition to measuring creatinine to measure kidney function. But clinicians and patients are often confused when the estimated HbA1c (derived from CGM) and the laboratory-measured HbA1c differ. Thus, “estimated HbA1c” is not the term that will be commonly used in the future. Glucose management indicator is the new term preferred by the Food and Drug Administration. Dr. Bergenstal and Dr. Sacks are coauthors of a paper explaining the GMI, published in November in Diabetes Care (Bergenstal RM, et al. 2018;41:2275–2280).

A1c certainly correlates with bad things happening, even on the large vessel side,” Dr. Bergenstal pointed out in his AACC presentation. “For every one percent increase in the A1c, there is a 17 percent higher chance of a patient having her first stroke, or 49 percent higher chance of having an ischemic stroke in people without diabetes, and a 24 percent increase in stroke in people with diabetes.”

HbA1c is also an important regulatory metric—for example, when it’s used to compare the performance of new drugs in improving A1c. “And now clinicians are being paid to achieve a certain A1c, so it’s a reimbursement metric as well.”

But, Dr. Bergenstal noted, “We can’t quite agree in the diabetes community on what the goal is for A1c. Is it six and a half? Is it seven? Is it eight?” The value of lowering HbA1c is clear when you are talking about reducing microvascular complications in type 1 and type 2 diabetes. “But there is a little more question when you talk about cardiovascular disease and mortality,” he said. “One large study even finds if you try to get an A1c that is perfectly normal, in some situations that can actually increase mortality.”

Even if the community could agree on a goal, HbA1c still falls short as a guide to managing patients, Dr. Bergenstal said. “A1c might be a good risk marker overall for the population, maybe even for an individual, but it doesn’t really help me get a better A1c.”

CAP TODAY
X