Diabetes :: Study Tests Oral Insulin to Prevent Type 1 Diabetes

University of Florida researchers have begun a clinical study of oral insulin to prevent or delay type 1 diabetes in people at risk for the disease.

The UF Health Science Center and Shands at UF are among 14 centers in the United States working with affiliate sites and participating physicians in Type 1 Diabetes TrialNet, a research group dedicated to the understanding, prevention and early treatment of type 1 diabetes.

?This is a unique opportunity to attempt to prevent the disease in relatives at risk for type 1 diabetes,? said Desmond Schatz, M.D., medical director of UF?s Diabetes Center of Excellence and principal investigator with the UF TrialNet Clinical Center. ?The intervention may also offer hope for delaying the onset of the disease.?

An estimated 1 to 2 million people with the disease have type 1 diabetes, which occurs when white blood cells vital to the body?s defenses against infectious diseases attack insulin-producing beta cells in the pancreas. The insulin these cells produce regulates how the body uses and stores sugar and other food nutrients for energy.

Research has shown the pancreas is resilient and more than half its insulin-producing beta cells must be irreversibly destroyed before an individual develops symptoms of the disease, which can take months or even years to occur.

That long period prior to the onset of symptoms provides an opportunity for interventions aimed at preventing the disease?s development, Schatz said.

In the study, University of Florida researchers are testing whether an insulin capsule taken by mouth once a day can prevent or delay type 1 diabetes in a specific group of people at risk for the disease.

An earlier trial suggested that oral insulin might delay type 1 diabetes for about four years in some people with islet cell autoantibodies in their blood. The presence of these autoantibodies alerts physicians to the destruction of insulin-producing cells up to 10 years before symptoms set in and indicates an individual is at greater risk of developing the disease.

For a person with high-risk genes and all three autoantibodies, the risk of developing diabetes in the next five years is greater than 50 percent, Schatz said.

?We hope that learning about the underlying immune events that set the stage for diabetes will help us identify ways to rein in the autoimmune attack on beta cells,? he said.

Animal studies have also suggested that insulin taken orally might even prevent type 1 diabetes. Some scientists think that introducing insulin via the digestive tract induces tolerance, a quieting of the immune system.

First- and second-degree relatives of people with type 1 diabetes who may be at risk are initially being screened through TrialNet?s natural history study, which is examining the immune and metabolic events that precede diabetes symptoms. Screening involves a simple blood test. Individuals enrolled in the natural history study are closely monitored for diabetes development and may be eligible to participate in the oral insulin trial or future studies that try to arrest the autoimmune process.

To lower blood sugar levels once diabetes occurs, patients need three or more insulin injections a day or treatment with an insulin pump. To prevent complications, they must regularly monitor their blood glucose, striving for a range that is as close to normal as possible.

Other diabetes studies under way at UF include a trial aimed at preserving insulin production in people recently diagnosed with type 1 diabetes, who often still have a supply of functioning beta cells. If these remaining beta cells can be protected with the help of insulin injections, more patients would be able to tightly control their blood glucose, preventing or delaying damage to the eyes, nerves, kidneys, heart and blood vessels.

Another TrialNet study seeks to turn off the body?s attack on beta cells with rituximab, a monoclonal antibody that binds to and temporarily destroys a class of immune cells. The rituximab trial is recruiting patients with type 1 diabetes diagnosed within the previous three months. Also under way is a study testing whether a combination of two drugs approved by the FDA to prevent rejection after an organ transplant can slow or arrest the autoimmunity of type 1 diabetes.

Lastly, the Environmental Determinants of Diabetes in the Young, or TEDDY, study aims to discover the genes and environmental exposures that may cause type 1 diabetes through a newborn screening program. Babies found to be at a high risk of developing the disease may enroll in TEDDY II and will be tracked over time to examine environmental risk factors.

The Type 1 Diabetes TrialNet studies are funded by the National Institutes of Health. The Juvenile Diabetes Research Foundation International and the American Diabetes Association also support the initiative.


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Diabetes :: Study tests oral insulin to prevent type 1 diabetes

Researchers have begun a clinical study of oral insulin to prevent or delay type 1 diabetes in at-risk people, the National Institutes of Health (NIH) announced today.

Type 1 Diabetes TrialNet, an NIH-funded network of researchers dedicated to the understanding, prevention, and early treatment of type 1 diabetes, is conducting the study in more than 100 medical centers across the United States, Canada, Europe, and Australia.

?Our goal is to prevent type 1 diabetes or to delay it as long as possible. If diabetes can be delayed, even for several years, those at risk will be spared the difficult challenges of controlling glucose and the development of complications for that much longer,? said TrialNet study chair Jay Skyler, M.D., of the University of Miami.

In the study, researchers are testing whether an insulin capsule taken by mouth once a day can prevent or delay diabetes in a specific group of people at risk for type 1 diabetes. An earlier trial suggested that oral insulin might delay type 1 diabetes for about four years in some people with autoantibodies to insulin in their blood. Animal studies have also suggested that insulin taken orally may prevent type 1 diabetes. Some scientists think that introducing insulin via the digestive tract induces tolerance, or a quieting of the immune system. Insulin taken orally has no side effects because the digestive system breaks it down quickly. To lower blood glucose, insulin must be injected or administered by an insulin pump.

In type 1 diabetes, a person?s own immune cells destroy the beta cells of the pancreas. Beta cells sense blood glucose and produce the hormone insulin, which regulates glucose and converts it to energy. The immune attack on beta cells begins well before a person develops diabetes and continues long after the disease is diagnosed. In the early stages of autoimmunity, up to 10 years before diabetes is diagnosed, autoantibodies may appear in the blood. These autoantibodies to glutamate decarboxylase (GAD), IA-2, and to insulin itself indicate a greater risk for developing type 1 diabetes. For a person with high-risk genes and all three antibodies, the risk of developing diabetes in the next 5 years is greater than 50 percent.

First- and second-degree relatives of people with type 1 diabetes who may be at risk are being screened through TrialNet?s natural history study, which is examining the immune and metabolic events that precede diabetes symptoms. Screening involves a simple blood test for the autoantibodies that signify diabetes risk. Individuals enrolled in the natural history study are closely monitored for diabetes development and may be eligible to participate in the oral insulin trial or future studies that try to arrest the autoimmune process.

Studies for the Newly Diagnosed

TrialNet studies are also aimed at safely preserving insulin production in people recently diagnosed with type 1 diabetes. In the few months after diagnosis, most patients still have a supply of functioning beta cells that, with the help of insulin injections, contribute to good control of blood glucose. If beta cells can be protected, more patients would be able to tightly control their blood glucose, which prevents or delays damage to the eyes, nerves, kidneys, heart, and blood vessels.

One TrialNet study seeks to turn off the immune attack on beta cells with Rituximab, a monoclonal antibody that binds to and temporarily destroys a specific class of immune cells. The Rituximab trial is recruiting patients with type 1 diabetes diagnosed within the previous 3 months. Rituximab is approved by the Food and Drug Administration (FDA) to treat specific forms of lymphoma and moderate to severe rheumatoid arthritis. It is not approved for the prevention of type 1 diabetes.

Also under way is a study testing whether mycophenolate mofetil (MMF) or MMF plus daclizumab (DZB), drugs approved by FDA to prevent rejection after an organ transplant, can slow or arrest the autoimmunity of type 1 diabetes. This study has recruited the needed number of patients.

Study for Newborns at Risk for Type 1 Diabetes

The Nutritional Intervention to Prevent Type 1 Diabetes (NIP) Trial is a pilot study of docosahexaenoic acid (DHA), an omega-3 fatty acid that may have anti-inflammatory benefits that prevent development of the autoimmunity that leads to type 1 diabetes. The NIP study is being conducted in:

babies less than 5 months old who have immediate family members with type 1 diabetes, and

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.

About 5 to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. Type 1 diabetes tends to arise in children and young adults but is also diagnosed in older people. Patients need three or more insulin injections a day or treatment with an insulin pump to maintain blood glucose control. To prevent complications, they must regularly monitor their blood glucose, striving for a range that is as close to normal as possible. The constant challenge of managing the disease poses an enormous burden on patients and their families.


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