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ORLANDO, Florida With more than 18 million Americans suffering diabetes and expectations for increases driven by rising rates of the disease in childhood the new products and services rolled out at this year's American Diabetes Association (Alexandria, Virginia) annual meeting, held last month at the Orange County Convention Center, are serving to profile the growing armamentarium of weapons being deployed in this ongoing fight.

In a poster presentation, researchers for Medtronic (Minneapolis, Minnesota) subsidiary, Medtronic MiniMed (Northridge, California) presented feasibility study results highlighting the potential benefits of "real-time" glucose readings in children with Type 1 diabetes using an external insulin pump and an external continuous glucose monitoring system.

A particular advantage that pump users enjoy, compared to patients using injections, is the flexibility to fine-tune and start or stop insulin delivery upon demand. Patients in the study used their pumps to make immediate therapy adjustments based upon real-time continuous glucose readings displayed every five minutes and by viewing a graph with 24-hour glucose trends, according to Medtronic MiniMed. The prototype sensor-augmented system used in the study, which is not yet FDA-cleared, will be evaluated in a larger study later this year.

At the four-week evaluation point of the study, 10 patients with Type 1 diabetes between the ages of 10 and 18 (median age 14.5 years) showed trends toward improved HbA1c (a decrease from 8% to 7.7%) and daily blood glucose levels (a decrease from 166 mg/dL to 154 mg/dL). Treatment changes were made based upon real-time glucose information gathered in this feasibility study, together with retrospective trend data. The mean absolute difference using 1,096 sensor-meter paired readings was reported to be 17%.

"Although the patient cohort was small and the blood sugar improvement was not statistically significant, we are encouraged by the outcome which showed positive trends in blood sugar control in only four weeks," said Francine Kaufman, MD, head of the Center of Diabetes and Endocrinology at Childrens Hospital of Los Angeles, professor of pediatrics at the Keck School of Medicine of University of Southern California (both Los Angeles) and immediate past president of the ADA. "Real-time readings and glucose trends allowed us to see where glucose levels were over the past 24 hours, where they were currently, and allowed us to project where they were going to be in the near future. This patient-empowering technology helped us improve diabetes management and certainly bodes well for the use of future sensor-augmented systems."

Studies have demonstrated that treating diabetes patients to a target HbA1c level of 6.5% to 7% and below can reduce their risk of diabetes-related complications as much as 76%, improve health and extend life.

An HbA1c test measures the average percentage of glucose concentration in the blood over a two- to three-month period. People without diabetes naturally maintain an HbA1c below 6%. However, roughly one-third of Americans with diabetes have an HbA1c above 9.5%, and elevated HbA1c levels can lead to serious short- and long-term complications of diabetes: blindness, kidney failure, amputation, impotence and heart disease.

"We are extremely encouraged by the results observed in this small patient population and look forward to initiating a large, multi-center study later this year," said Jeffery McCaulley, vice president and general manager of Medtronic's diabetes business. "The ability for patients to accurately receive real-time glucose readings and make immediate diabetes management adjustments will be a major step toward the creation of an artificial pancreas."

When commercially available, this new therapy is expected to be marketed as the Paradigm 522/722 sensor-augmented insulin pump system. This external system will be designed to utilize a subcutaneous glucose sensor, which is inserted under the skin by a patient or healthcare professional, to continuously record blood sugar readings for up to three days. The system's small transmitter is designed to send continuous glucose readings via radio frequency to the pump, which is expected to display real-time glucose readings every five minutes, trend graphs and provide hypoglycemia and hyperglycemia alerts to patients, enabling them to monitor trends in their blood sugar levels and make immediate corrective adjustments using their insulin pump.

More focus needed on BP, cholesterol

Several reports issued at the meeting indicated that diabetes patients and their doctors are failing to give cholesterol and blood pressure control the attention needed to reduce the high risk for heart attacks and strokes in diabetes. "Diabetes management requires equal attention to control of blood glucose, cholesterol, blood pressure and other cardiovascular risk factors but it's not happening, as today's research reports show," said Eugene Barrett, MD, PhD, president of the ADA. "Physicians around the world and their patients are failing to make the link science has long since proven that two out of three people with diabetes die from heart disease and stroke."

Two reports showed that only 37% of people with diabetes achieved LDL cholesterol levels of less than 100 mg/dL, as recommended by the association. (LDL-C is the so-called "bad" cholesterol closely associated with cardiovascular disease).

A third report showed that, despite the efforts of the ADA and other organizations, most diabetes specialists around the world still do not consider diabetes a "coronary equivalent" and still do not have low enough LDL-C goals for their diabetes patients.

A fourth report showed that almost half of those with diabetes have uncontrolled hypertension and that up to 75% of those in the study who also had kidney disease had uncontrolled hypertension.

The first study retrospectively reviewed a group of 9,642 enrollees with diabetes in a major HMO in Michigan, according to Manel Pladevall, MD, clinical epidemiologist at the Center for Health Services Research in the Henry Ford Health System (Detroit, Michigan). Researchers assessed what percentage of those people were tested for LDL-C, what percentage were treated and what percentage achieved the goal of <100 mg/dL at five time points over the course of five years starting in 1997.

The percentage of patients who reached LDL-C levels of <100 mg/dL improved from 22% to only 37% over five years through 2001, despite a near-doubling of the percentage of patients tested for LDL-C.

The second study reviewed the database of a 1.1 million member managed care group in the southeastern U.S. Researchers at Health Core (Wilmington, Delaware), a health outcomes and clinical research group, identified 8,855 people with diabetes who were tested for cholesterol levels between Oct. 1, 1999 and Sept. 30, 2000. They found that only 37% of these people were at the LDL-C cholesterol goal of <100 mg/dL three years later.

The third study, known as the AUDIT Study, was a worldwide survey of physician attitudes comparing practice patterns related to lipid levels in people with Type 2 diabetes. "AUDIT was designed to help discern a paradox: while mounting evidence from clinical trials has proven that people with diabetes benefit from lipid-lowering therapy, which reduces their risk of heart attacks and strokes, only a minority of patients actually achieve healthy lipid goals," said Lawrence Leiter, MD, head of the division of endocrinology at St. Michael's Hospital and a professor at the University of Toronto (both Toronto, Ontario).

"Despite the recommendations of the American Diabetes Association and other organizations around the world, that people with diabetes have their cholesterol managed as aggressively as people with heart disease, our survey of diabetes specialists in 50 countries showed this is not happening," Leiter said.

The survey showed that the targets that diabetes specialists set for their patients are frequently not as low as their professional organizations recommend. In their daily clinical practice, many diabetes specialists still do not recognize that diabetes is a "coronary equivalent." Some 45% of physicians have a different LDL-C goal for people with cardiovascular disease (CVD) vs. those without CVD; 85% of physicians have an LDL-C goal of <100 mg/dL for those with CVD vs. 59% for people with diabetes but without CVD.

Leiter said diabetes specialists estimate that only about half of their patients with Type 2 diabetes achieve the cholesterol goals set for them goals that may not be low enough to begin with. He said the physicians surveyed perceive the primary barrier to goal-achievement to be patient compliance, i.e., the traditional tendency to blame the patient.

The fourth report focused on uncontrolled blood pressure found in a free screening program offered to individuals 18 years or older who had a personal or family history of diabetes, hypertension or kidney disease. Some 10,043 participants with complete data were reviewed.

"Almost half 48.7% of those who had diabetes but no kidney disease were found to have uncontrolled hypertension," reported Janet McGill, MD, associate professor of medicine in the division of endocrinology, metabolism and lipid research at Washington University (St. Louis, Missouri). Among those who had kidney disease, uncontrolled hypertension increased with each stage of the disease and ranged from 55% to 75%. Further, the prevalence of uncontrolled hypertension was significantly higher in people with diabetes, compared to those without, across the spectrum of kidney function, from normal to severely impaired.

Teleconference program unveiled

A program that uses videoconferencing to bring pediatric diabetes specialists to families in underserved areas of Florida was introduced at the meeting. The video teleconferencing program, established in 2002 to improve access to pediatric diabetes care, is called the Florida Initiative in Telehealth and Education (FITE).

All children and teens in the program were enrolled in Medicaid and/or Children's Medical Services of Florida, a program designed, it said "for families with overwhelming health costs and inadequate financial resources."

Previously, clinics were held every three months requiring 2 1/2 hours of travel time in each direction to and from the university. Two doctors, a nurse and a nutritionist traveled to a small local clinic in Daytona and tried to see about 40 children in one day. Any children who missed their appointments either had to travel to Gainesville or wait until the next clinic session and therefore often were not seen by a pediatric diabetes specialist for six months.

"Our telemedicine program saves healthcare dollars, extends the outreach of scarce pediatric diabetes specialists and has improved the health of our children and teenagers with diabetes," said Toree Malasanos, MD, assistant professor of pediatric endocrinology at the University of Florida College of Medicine (Gainesville, Florida). "Replication of our video teleconferencing program around the country would be an excellent way to avoid the enormous waste of travel time and expense that remote programs incur while improving patient outcomes," she added.

Only some 700 board-certified pediatric endocrinologists many of whom don't practice full time because they do research are available to care for the more than 200,000 U.S. children and teens with diabetes, and many clinics have long waiting times for appointments, according to Malasanos.

"This shortage will only worsen, especially in view of the growing number of overweight children and teens now developing Type 2 diabetes," she said. Malasanos said that the long delays in visits "can be an extremely serious problem in many pediatric diabetes situations because growing children may need more frequent changes in their insulin regimen."

After two years, the outcomes for youngsters in the program have been described as "dramatic." Before FITE, the group averaged 13 hospitalizations per year 47 hospital days per year. This has decreased to three hospitalizations per year nine days per year. The average number of emergency room visits per year for the group has decreased from eight to 1.5 per year. Further, the total financial savings over two years amounted to more than $38,000, based on the reduction in hospital days and emergency room visits and taking into account equipment and communication costs, but not accounting does for savings in travel costs.

Tighter control pays off

New research findings released at the ADA sessions have shown that tight control of Type 1 diabetes pays off in reduced rates of nerve damage years later, when control has become less intense, possibly due to mechanisms beyond blood glucose levels alone. "People who were treated with intensive therapy to try to keep their blood glucose levels as close to normal as possible for an average of six years continue to demonstrate a lower risk for developing neuropathy, compared to those who were never treated with such intensive therapy, even eight years after the period of intensive therapy ended," said Catherine Martin, MS, a study coordinator at the University of Michigan (Ann Arbor, Michigan). Those who had previously been on intensive therapy were about one-third less likely to develop nerve damage years later, even though their control had become less intense. "The take-home message is that good glucose control should be started as early as possible," said Martin.

In another report at the ADA, the Edmonton Protocol for transplanting islets, through an injection that frees people with diabetes from daily insulin injections, has been shown to be effective and safe in its first international multicenter trial, according to a report released during the ADA sessions. "We are delighted that the success of the protocol has now been replicated internationally in our Immune Tolerance Network trial, in which nine centers in the U.S., Canada and Europe have participated over the past four years," said James Shapiro, MD, PhD, director of the Clinical Islet Transplant Program, University of Alberta (Edmonton, Alberta).

The Edmonton Protocol breakthrough occurred, the researchers said, because of exquisite care in the isolation and preparation of islets; use of a unique drug combination and timing of their use to protect the islets and prevent their rejection; and selection of only patients most likely to benefit from the transplant and participate successfully in the trial.

Shapiro reported that 19 of 36 participants continue to be insulin-independent for up to one year of follow-up after their transplant five of them having achieved such independence after only one infusion, seven after two infusions, and seven more after three infusions. Of the 17 participants who continue to require insulin, seven have derived some benefit with ongoing partial islet graft function and improvement in their ability to manage their diabetes.

Elsewhere at ADA

Abbott Laboratories (Abbott Park, Illinois), through its recently formed Abbott Diabetes Care (Alameda, California) unit, introduced the new iteration of its Precision Xtra Advanced Diabetes Management System. The new monitor is designed to offer advanced diabetes management as well as measure both blood glucose and blood ketone with a single monitor.

Abbott said that Precision Xtra is the first home glucose monitor that also allows people with diabetes to test their blood for ketone levels. Elevated ketone levels can signify a risk for developing diabetic ketoacidosis (DKA), a life-threatening condition caused by acute insulin deficiency. DKA must be recognized and treated as soon as possible in order to prevent serious illness or even death. In addition, the ADA affirms that blood ketone testing is preferred over urine ketone testing as a more reliable method of diagnosing diabetic ketoacidosis.

"Proper and regular blood glucose testing is one of the most important ways to manage diabetes," said Arturo Rolla, MD, assistant clinical professor of medicine, Harvard Medical School (Boston, Massachusetts). "The Precision Xtra Advanced Diabetes Management System with the unique blood ketone testing capability provides people with diabetes an effective and convenient method for ketone testing and an opportunity to better manage their condition."

The new system will be available for sale in 3Q04, the company said. Abbott Diabetes Care was formed via the $1.2 billion merger of Abbott's MediSense (Bedford, Massachusetts) business with TheraSense (also Alameda) in April.

The ADA is working to make it easier for people with diabetes, and those at risk for the disease, to take more control of their health with a new tool that can be used to make better healthcare decisions and developed as part of the association's new initiative, "Doing Better: Tools for Diabetes Care." Previewed at the annual meeting, the Diabetes Personal Health Decisions Tool, or "Diabetes PHD," is an interactive web-based technology that enables people to enter personal health parameters such as age, sex, height, race, weight, family history, medications and a variety of blood values, and then receive in return an accurate risk profile.

Most important, the risk profile will provide a concrete picture of how the individual can alter his or her risk by changing modifiable health parameters such as weight, blood pressure or cholesterol. The tool will help both patients and health professionals make informed choices about how best to reduce a patient's risk for diabetes and its complications. Free and accessible on ADA's web site, the tool will be publicly launched later this year. The underpinning software is Archimedes, developed by Kaiser Permanente (Oakland, California) and described as an extremely comprehensive model that simulates both the underlying biology impacting the development of diabetes and a variety of risk factors, medications and treatments on outcomes relevant to people with diabetes.

Emisphere Technologies (Tarrytown, New York) reported that results from a multiple-dose clinical study of an oral insulin tablet using its eligen technology were presented as a poster at the meeting. The study was conducted at Profil Institute (Neuss, Germany), an internationally recognized diabetes research center. Lead investigator Tim Heise, MD, said that treatment with Emisphere oral insulin was well tolerated, led to improvements in post-prandial blood glucose concentrations both under oral glucose tolerance test (OGTT) and standardized meal conditions, and tended to improve fasting blood glucose concentrations and insulin resistance.

Heise termed the results from the pilot study "very promising," adding that the study "confirmed oral insulin could achieve an early indication of glycemic control in a modest sized patient population."

The ADA announced a collaboration with Entelos (Foster City, California) to initiate a research program aimed at preventing Type 1 diabetes. Entelos is pioneering in silico research and the use of computer models to advance pharmaceutical R&D. The in silico research platform will initially be used by Entelos and certain academic research laboratories to address key scientific questions related to the onset and progression of the disease. The first academic centers to receive the technology will be those led by members of the ADA's Type 1 diabetes scientific advisory board, which has been formed to provide scientific guidance and oversight to the collaboration. Over time, the platform will be made available to other academic researchers through the association's grant process.

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