Medical Device Daily Washington Editor

WASHINGTON – Real-time continuous glucose-monitoring systems, which are just now coming of age, suggest a paradigm shift for sufferers of diabetes. While they do not yet offer the accuracy of the traditional pinprick glucose test, the very existence of these monitors holds the promise of a more normal life for diabetics, especially for sufferers of Type 1 (juvenile) diabetes when coupled with an insulin pump.

Diabetes is a sufficiently prominent public health concern that the FDA has listed the “artificial pancreas” in its Critical Path Initiative, and the Juvenile Diabetes Research Foundation (JDRF; New York) also has made the development of an artificial pancreas a major initiative.

Diabetics got a bolus of good news on April 13 when the FDA reported its approval of the premarket approval application for the MiniMed Paradigm, a combined insulin pump/glucose monitor device made by Medtronic (Minneapolis). Thus, the JDRF had much to celebrate when it held its annual conference here last week.

However, the advent of combination systems is not quite the end of the search for diabetics. While medical advances have been impressive, the $900 million that JDRF has raised and channeled into research since its inception in 1970 has not yet made diabetes a hands-off and worry-free state of affairs for all its sufferers. This is because any unusual readings generated by the MiniMed Paradigm must be confirmed by the traditional glucose test method. Also, the patient still has to augment the pump's function, especially if the system alerts the patient that their glucose levels have slipped out of bounds.

Most Americans have a rough idea of the prevalence of the disease. As many as 3 million Americans suffer from Type 1 diabetes, which appears in childhood as the result of an autoimmune disorder that shuts down pancreatic production of insulin. According to the American Diabetes Association (Alexandria, Virginia), diabetes of both kinds consumed $132 billion in healthcare costs in 2002, and more than 13,000 new diagnoses are made each year.

Despite the fact that diabetes has not been beaten, these new medical technologies demonstrate that researchers have covered a lot of ground. However, Medtronic might not have the market to itself for long.

DexCom (San Diego, California) has FDA approval to market the STS Sensor, another continuous monitor, and Abbott Labs (Abbott Park, Illinois) is working to obtain FDA approval for the Navigator Sensor. It seems only a question of time before one or both of these companies bundles their sensors with a glucose pump and expand the patient's array of choices. Both Medtronic's Paradigm and the Freestyle Navigator rely on samples of interstitial fluid at five-minute intervals to detect glucose levels. Interstitial fluid measurements typically track those of blood with about a five-minute delay.

While the Paradigm and Navigator represent groundbreaking advances, they are not quite the hands-off devices as embodied by the idea of the “closed-loop” system. As noted previously, patients on the MiniMed must occasionally supplement the function of the meter/pump combination, especially at meal times. An area of perhaps even greater concern is nighttime glucose levels. Parents of children with Type 1 diabetes must awake several times a night to check their offsprings' glucose levels, but the arrival of a combination meter and pump may shortly mean that Mom and Dad can stay in bed all night.

JDRF awarded Robert Tamborlane, MD, deputy director of the Yale General Clinical Research Center (New Haven, Connecticut) with the fifth annual JDRF Excellence in Clinical Research award at the conference. He gave an historical perspective on the research of diabetes, noting that he was in practice in the “bad old days in the 1980s when our children were under horrible metabolic control.”

Tamborlane pointed out that in the “early days,” researchers often were working “in their garages,” figuratively speaking, on treatment modalities for diabetes, but that the JDRF funding for research, along with interest in universities and the private sector, have spurred the development of much more advanced devices and drugs to treat diabetes.

He said that in the current approved use of the Minimed system, the meter can be set to begin pumping insulin at 120 mg/dl rather than a more common trigger point of 90, making it “extremely unlikely that you ever” get below a safe level of blood glucose (serum glucose readings up to 100 mg/dl are considered normal, and a reading between 100 and 126 mg/dl suggests a pre-diabetic state. Anything higher than 126 is almost certainly indicative of diabetes).

Tamborlane also said that most of the “severe hypoglycemic events that occur in patients with Type 1 diabetes occur during the night when the patient is sleeping. An important factor that contributes to the risk of nocturnal hypoglycemia is that the body's defense system against hypoglycemia (i.e., the release of anti-insulin hormones epinephrine and norepinephrine and cortisol) is also sleeping – there is no rise in these hormones in response to falling blood glucose levels at night.”

As for the ability of the MiniMed Paradigm to exert exact control of the insulin/glucose mechanism, he admitted that the after-meal levels of insulin are “higher than we would like,” but that the knowledgeable user would be able to compensate with a “priming dose” to reduce these out-of-specification levels.

At present, the sensors used in the Medtronic unit have to be changed every three days, but Steve Sabicer, a senior manager in Medtronic's public relations office, said that the rate of infections was much lower than 1% and that efficacy was not the issue. Previous clinical experience has been the primary determinant of the useful life of these sensors, he noted.

Reimbursement for monitor/pump devices is one of the objectives of JDRF. On the subject of coverage by the Centers for Medicare & Medicaid Services (CMS; Baltimore), Cynthia Rice, JDRF's director of new technology access, said that while the association will communicate extensively with the CMS to prompt the agency to cover such devices, she noted that “there are times when private plans lead CMS” in coverage of diabetes treatments.

Rice also suggested that given the morbidities most Type 1 sufferers encounter later in life, “it would help Medicare's bottom line” if private payers offered coverage.