CHICAGO — Major changes are afoot for both the diagnosis and monitoring of diabetes as research has shown there is a substantial need for improvements.

Experts in the glucose monitoring field sounded off at the American Association for Clinical Chemistry's (AACC; Washington) annual meeting this week with research showing that the accuracy of glucose meters – which can be wrong by up to 20% – is no longer acceptable because the imprecision can lead to dosing errors and the ensuing complications of hyperglycemia or hypoglycemia. Groups are pushing to up the standards for all meters to an error rate of 5% or less and for hospitals to stop using them, particularly in intensive care units (ICU).

Also, new guidelines coming from the National Academy of Clinical Biochemistry, a section of the AACC, recommend the use of hemoglobin A1c (HbA1c) to diagnose diabetes, replacing the glucose gold standard test.

"It's hard to know at what level of error patients are harmed by imprecise meters," David Bruns, MD, director of clinical chemistry and toxicology and associate director of Molecular Diagnostics Laboratory, University of Virginia (Charlottesville) told Medical Device Daily. "In the first study I published on this topic, all we could say was that as meter errors go up there are dose errors. But we didn't carry it further to see at what level it leads to hypoglycemia. To my knowledge, I'm not aware of other studies that have come out since our study."

That study, first examining the meter error rates via computer modeling, was published in Clinical Chemistry in 2001. Since then Bruns and his colleagues have continued to focus on meters, but he has been unable to attract funding to do further studies that compare the imprecision of meters.

Bruns led a session today at the AACC titled "How Accurate Are Glucose Meters? How Accurate Do They Need to Be?" His lecture is based on studies he and colleagues performed that reveal performance specifications established by the American Diabetes Association (ADA; Alexandria, Virginia) could lead to dosing errors in up to 23% of insulin doses, while devices that conform to Clinical Laboratory Improvement Amendments (CLIA) '88 standards are susceptible to errors in 16% to 45% of dosing events.

He re-emphasized the dire need for outcomes studies to determine if dosing errors pose serious threats to diabetics and whether current technical specifications are sufficient to match clinical need.

"Frankly, I've never found anybody interested in funding such a study," he said. "It's not like a drug study where you can spend tens of millions of dollars and, if a drug works, it can make billions of dollars. But the meter market is now in the billions of dollars and you'd think somebody would want to fund a trial."

Despite that, enough evidence exists to motivate the ADA and the FDA to take action.

The American Association of Clinical Endocrinologists (Jacksonville, Florida) has formally opened the matter with the FDA and the agency reported late last month that it is recommending reform of International Standard Organization (ISO) requirements for glucose meters.

Bruns said that he's particularly concerned with tight glucose control of critically ill patients in hospitals, as outlined in an upcoming paper he co-authored in Clinical Chemistry entitled "Tight glucose control in the intensive care unit: are glucose meters up to the task?" An earlier paper revealed such control protocol results in a 34% reduction in ICU mortality.

"How good are the meters that are on the market? Plus or minus 20% error rate was OK and it's been out there now for 20 years. Most of the newer ones hit 15%. Now the ADA wants 5%. The ISO wants something different," he said.

When asked if companies such as Medtronic Diabetes (Northridge, California) are putting the cart before the horse in developing a device that combines both a meter and a pump before meters have a better error rate, Bruns said accuracy can be improved with such devices because they automatically take glucose measurements more frequently than people do manually, reducing the chances of errors in dosing (Medical Device Daily, June 10, 2009).

"If you have a system that can make measurements four times an hour then random error isn't such a big deal," he said. "In those cases, you can withstand the imprecision."

A1c – The new gold standard?

In addition to the evolution of glucose meters, another presentation at the AACC conference reported data from a new study from the International Expert Committee (IEC) that recommends the use of HbA1c rather than glucose for diagnosis of diabetes.

The test has been used for decades to measure long-term glycemic control in diabetics, but glucose was the primary test for diagnosing the disease.

The IEC included members appointed by the ADA, the European Association for the Study of Diabetes (D sseldorf, Germany) and the International Diabetes Federation (Brussels, Belgium).

"The report is being considered by the relevant committees of each of these groups," said David Sacks, MD, medical director of clinical chemistry, Brigham and Women's Hospital (Boston), who said, "Although the specific details of the recommendations to be proposed by these bodies have not been decided, it appears highly likely that all of the major clinical diabetes organizations will adopt HbA1c measurement for the diagnosis of diabetes."

Sacks authored an editorial to appear in the August issue Clinical Chemistry, titled "The Diagnosis of Diabetes is Changing: How Implementation of Hemoglobin A1c Will Impact Clinical Laboratories."

He moderated a symposium here this week called "Laboratory Medicine Practice Guidelines for Laboratory Analysis in Diabetes" where various speakers vetted criteria for screening and diagnosing diabetes and the ADA criteria for diagnosing diabetes in pregnant women.