A Medical Device Daily

The National Institutes of Health (NIH; Bethesda, Maryland) reported at the annual scientific meeting of the American Diabetes Association (ADA; Alexandria, Virginia) that 18 medical centers in the U.S., Canada, Europe and Australia have begun new clinical studies in Type 1 diabetes.

The NIH-funded studies seek to slow or stop the immune system's attack on insulin-producing cells in two groups of people: those newly diagnosed with Type 1 diabetes and those at risk for developing it.

“It would be a tremendous step forward if insulin-producing cells can be shielded from further destruction by immune cells,” said NIH Director Elias Zerhouni, MD. “We stand to learn a great deal from these promising studies, which are exploiting the knowledge gained from earlier research in immunology, endocrinology, and the biology of Type 1 diabetes.”

Type 1 diabetes accounts for 5% to 10% of diagnosed diabetes cases in the U.S. – up to 1 million people. Formerly called juvenile onset diabetes, Type 1 diabetes usually develops in children and young adults. People with this form of diabetes typically need three or more insulin injections a day or treatment with an insulin pump, as well as careful monitoring of blood glucose and attention to diet and exercise, to properly control their blood glucose.

Immune destruction of beta cells begins well before a person develops the symptoms of diabetes and continues long after the disease is diagnosed. During the months after diabetes is diagnosed, most patients still have a reservoir of functioning beta cells that, with the help of insulin injections, makes it easier to control blood glucose. If the “honeymoon” period can be extended, researchers hope that more patients would be able to tightly control their blood glucose.

Researchers participating in Type 1 Diabetes TrialNet are conducting two studies that seek to safely preserve insulin production in people diagnosed with Type 1 diabetes in the previous three months.

“The more beta cells a person has, the easier it is to control diabetes and prevent complications,” said TrialNet chair Jay Skyler, MD, of the University of Miami (Coral Gables, Florida). “With these studies, we hope to stop the immune system's attack on these cells and keep the disease from getting worse.”

A number of studies have already shown how a subgroup of T cells, the “warrior” cells of the immune system, seek out and attack insulin-producing cells. B cells, another group of immune cells that were initially seen as idle bystanders, are now thought to raise the alarm by presenting antigens to T cells, urging them to take action.

This new insight is being tested in a study that seeks to “turn off” the alert by reducing the number of circulating B cells. In this study, researchers are testing the use of Rituximab, a monoclonal antibody that binds to a receptor on the surface of B cells and destroys them.

Some studies show that the immune destruction of beta cells is linked to an inflammatory process triggered by specific cytokines, molecules that regulate communication among immune cells. TrialNet researchers hope to quell this inflammation and prevent the development of autoantibodies with docosahexaenoic acid (DHA), an omega-3 fatty acid that may have anti-inflammatory benefits.

Nutritional Intervention to Prevent Type 1 Diabetes (NIP) is a pilot study of DHA being conducted in babies less than 5 months old who have immediate family members with Type 1 diabetes. The NIP study also is screening pregnant mothers in their third trimester whose babies are at risk for Type 1 diabetes, either because the mother has Type 1 diabetes herself or other immediate relatives have the disease.

TrialNet researchers also are probing the causes of Type 1 diabetes by examining the immune and metabolic events that precede the onset of diabetes symptoms. They are screening two groups of relatives of those with Type 1 diabetes: first-degree relatives ages 1 to 45 and second-degree relatives ages 1 to 20.

Screening involves a simple blood test for the autoantibodies that appear in at-risk people years before diabetes develops. The presence of autoantibodies to GAD, IA-2 and insulin point to a greater risk for developing Type 1 diabetes. For a person with high-risk genes who has all three antibodies, the risk of developing diabetes in the next five years is greater than 50%.

Also at the ADA meeting:

• Abbott Diabetes Care (Alameda, California) cited the presentation of results from two new studies that met the predefined endpoints designed to assess the accuracy, safety and efficacy of the FreeStyle Navigator Continuous Glucose Monitoring System for children and adults. Both studies were presented during poster sessions.

The FreeStyle Navigator continuous glucose monitoring system is an investigational device under FDA review. The system includes a five-day sensor, a transmitter and a wireless receiver with a built-in FreeStyle blood glucose monitoring system. The system is designed to provide glucose readings once per minute, high/low glucose alarms and projected glucose alarms.

In an NIH-funded DirecNet trial of 30 children (ages 4 to 17) in both inpatient and outpatient settings, FreeStyle Navigator system accuracy and precision were sustained for five days of wear and were similar in different insertion locations (arm, abdomen or hip). In addition, accuracy of the system was similar during inpatient use and when used at home, and it was accurate during exercise and after meals.

“The need for frequent blood glucose monitoring remains a barrier to achieving excellent diabetes control. An accurate, real-time continuous glucose system such as FreeStyle Navigator would provide valuable information for improved diabetes management,” said Peter Chase, MD, professor of pediatrics and clinical director emeritus of the Barbara Davis Center for Childhood Diabetes at the University of Colorado Health Sciences Center (Denver). “These data are promising and suggest the potential value of FreeStyle Navigator in the management of Type 1 diabetes in both children and adults.”

Ed Fiorentino, president of Abbott Diabetes Care, said, “Based on the promising results obtained from the NIH DirecNet study, and via other clinical studies we hope to initiate, Abbott intends to file a supplemental PMA with the FDA for a pediatric indication in the post-approval period.”

In a second study, the safety and efficacy of the FreeStyle Navigator system was evaluated in the home use environment in 123 Type 1 and Type 2 diabetes subjects who completed the study. The data obtained from this trial were submitted to the FDA as part of Abbott's PMA for the FreeStyle Navigator system.

The study was designed for a total of 40 days of sensor wear (arm or abdomen), with performance evaluated through a comparison between more than 11,000 values obtained from the FreeStyle Navigator system and simultaneous pairs of blood glucose values. The overall mean absolute relative difference in these values was 14.4 +/- 13.4%, and in a Clarke Error Grid (CEG) analysis, 96.8% of the values fell in zone A or zone B. The CEG compares readings from a lab reference to a reading from a glucose monitoring device at a specific point in time.

• Results of a study by a group of clinicians at the Chaim Sheba Medical Center (Tel Hashomer, Israel) indicate that the NBM-100G, a noninvasive continuous glucose monitoring sensor developed by OrSense (Nes Ziona, Israel), accurately measures levels of glucose in a home-like setting.

The study consisted of three phases: one focused on low glucose levels and two additional trials that simulated home use, including night time measurements. The trials consisted of 107 daily sessions measuring 24 subjects, 11 females and 13 males, between the ages 20-74; 14 subjects were Type 1 diabetes patients and 10 were Type 2.

In all three trial settings, the results provided by the NBM-100G were compared to measurements obtained by conventional invasive methods collected every 20 to 60 minutes. The range of the glucose levels measured in the study was 38 to 485 mg/dl. The resulting median relative absolute difference was 12.9%. A Deming Regression yielded a slope of 0.94 and a Clarke error grid analysis showed that 95.3% of the measurements fell within the clinically accurate and acceptable zones A and B.