The "gold standard" test that diabetics have relied on for years to measure their glucose levels may be a good test for averaging a person's glucose levels over a period of two to three weeks, but it can miss dangerous glycemic swings, according to GlycoMark (Winston Salem, North Carolina/New York).

The company presented research Saturday at the American Diabetes Association (ADA; Alexandria, Virginia) meeting in New Orleans that suggests its test should be used as adjunct to the A1C blood test. The GlycoMark test is designed to accurately reveal dangerous swings in blood sugar that are undetectable by A1C, the company said.

Although the A1C has been the gold standard for many years for measuring glucose levels, GlycoMark President Eric Button told Medical Device Daily, the key word is average (mathematically speaking). "In statistics the first thing they teach you is that averages can be somewhat misleading – they can be accurate, but misleading – you can have very high high's and very low low's and it averages out to be a reasonable level," Button said. "So what can happen in particular in Type 1 patients is that high glucose levels can be averaged out by low levels and then your A1C value can look reasonable, in fact it can even look normal, and that can be misleading."

Button pointed out that even healthy people have ups and downs in their glucose level but for a diabetic whose ups and downs can be extreme, it's like riding a roller coaster. Yet, if they go by the A1C test, those swings may not show up.

The GlycoMark test, on the other hand, is designed to reflect glucose levels that are only high so that the "wild swings" will not get averaged out, Button said. But the study suggests the A1C test and GlycoMark's test should be ordered together, the company said. "In case you have an A1C look normal and an abnormal GlycoMark value it would indicate that the patient is having significant glucose swings and then you would want to treat the patient accordingly," he said. If the physician treating the patient just went by the A1C value it would look like the patient did not need to be treated, whereas the GlycoMark results would indicate that treatment is necessary, Button said.

"So in essence you'd want to use both tests, it makes the diagnostic picture more complete," Button said.

The results were from the ongoing DURABLE clinical trial showing that the GlycoMark blood test is a better reflection of glucose, particularly after-meal glucose levels, than the gold standard hemoglobin A1C test in moderately controlled patients with diabetes, according to the company. Kathleen Dungan, MD, of Ohio State University (Columbus) and investigators from Eli Lilly & Co. (Indianapolis) reported the findings. It is the largest clinical study to evaluate the use of GlycoMark to reflect after-meal glucose levels with 2,094 patients enrolled from 11 countries. The DURABLE trial (Assessing the Durability of Basal vs. Lispro Mix 75/25 Insulin Efficacy) confirms results from a smaller population study completed by John Buse, MD, of the University of North Carolina, Steven Wittlin, MD, of the University of Rochester, and Dungan in June 2006.

In the study, the 1,5-Anhydroglucitol blood test (GlycoMark) correlated more strongly than hemoglobin A1C with all self-monitored plasma glucose (SMPG) parameters, particularly after-meal glucose levels, in moderately controlled patients with A1C levels less than 8%. "The data support the use of 1,5-anhydroglucitol, in conjunction with A1C, in moderately controlled patients with Type 2 diabetes," Dungan said.

The GlycoMark already is FDA-approved and on the market, and it is available at major reference laboratories including Quest Diagnostics and LabCorp.

"This large clinical study validates the important role of the GlycoMark test to effectively monitor patients with diabetes," Button said. "Although patients may appear to be adequately controlled by A1C results, it may not readily reveal elevated postprandial spikes which are associated with dangerous cardiovascular complications. GlycoMark can detect 'hidden' glucose spikes, allowing physicians to target these spikes with specific treatments."

The company also reported that in a retrospective examination of studies evaluating the use of GlycoMark to monitor exenatide, pramlintide, sitagliptin, and biphasic insulin therapies, GlycoMark reflected changes in aftermeal glucose levels more dynamically than A1C in moderately controlled patients – underscoring the ability of GlycoMark to detect underlying treatment effects on after-meal glucose not revealed by A1C.

Also at the ADA meeting, Medtronic Diabetes (Northridge, California) has reported results of a randomized, controlled trial to demonstrate the benefits of an insulin pump therapy augmented with real-time continuous glucose monitoring (Personal CGM) vs. a conventional pump and self-monitoring of blood glucose in type 1 diabetes patients with poor metabolic control. Study findings showed that patients who used Personal CGM more than 70% of the time achieved nearly a full percentage point reduction in A1C (average blood glucose levels).

"The REAL Trend study validates a growing body of clinical evidence that demonstrates the power of combining insulin pump therapy with Personal CGM," said Chris O'Connell, president of the Diabetes business and senior vice president at Medtronic. "As the clinical evidence continues to build, we are seeing an impressive increase in CGM adoption globally."

The six-month, multi-center REAL Trend study was designed to determine whether patients with poorly controlled A1C (about 8%) who used multiple daily injections could improve their metabolic control with the MiniMed Paradigm REAL-Time System (insulin pump augmented with Personal CGM) vs. a conventional insulin pump and self-monitoring of blood glucose levels. The study enrolled 132 patients in France including 51 children age two and up.

"Diabetes is a complicated disease, and technologies like insulin pump therapy and Personal CGM can help patients best manage short- and long-term outcomes," said Dr. Francine Kaufman, chief medical officer of the Diabetes business at Medtronic. "This study reinforces the need for an integrated, management approach that uses multiple technologies to achieve significant results. Combining an insulin pump with Personal CGM and therapy management software are powerful tools for patients wanting to achieve optimal control."

As evident in previous studies, sensor compliance drove increased improvement of glycemic control, reflected by lower A1C results without increased hypoglycemia in the REAL Trend study. Among the compliant patient population, investigators saw a significant difference in each treatment group and between groups from baseline to study end, including an A1C reduction of 0.96% among the group fitted with the MiniMed Paradigm REAL-Time System. The conventional insulin pump arm only saw a 0.55% reduction. In the full study population, A1C measurements decreased in each treatment group without reaching statistical significance between the two groups from baseline to study end. This may be attributed to use of the CGM device less often than prescribed (70% of the time).

Medtronic said this study also reinforced the superiority of insulin pump therapy over multiple daily injections for poorly-controlled type 1 patients. Across study populations, A1C levels improved significantly after treatment was changed from multiple daily injections to a conventional insulin pump or an insulin pump augmented with personal CGM. Studies have shown that reducing A1C can result in reduced risk of long-term side effects associated with diabetes, including blindness and kidney disease.

According to the Centers for Disease Control and Prevention (Atlanta), diabetes affects nearly 24 million Americans. Of that, nearly one-quarter, or 6 million people, do not know they have the disease. Diabetes is the sixth-leading cause of death in the U.S. and costs about $174 billion per year in direct and indirect medical expenses.