Florida Researchers Embark On Major Studies Of Oral Insulin Capsule For Diabetes

April 25, 1996

GAINESVILLE—In two new nationwide studies, an oral insulin capsule will be tested for the first time in hundreds of people in an attempt to prevent or stall the onset of insulin-dependent diabetes.

University of Florida researchers, whose discoveries have helped lay the foundation for the studies, are at the forefront of a worldwide effort to better understand the disease.

Diabetes is a serious, lifelong disease afflicting more than 1 million Americans. The disease can lead to blindness, kidney failure, heart attacks and circulatory problems that sometimes require amputation of affected limbs. Total diabetes health-care costs in the United States exceed $120 billion, and insulin-dependent diabetes accounts for a disproportionate share of those costs.

Hundreds of study participants will have to be tracked for years before physicians know whether the capsule — taken every day before breakfast — is effective. But for diabetics who must endure daily insulin injections, not to mention the disease’s troubling side effects, the studies are an encouraging first step:

  • In the second phase of a two-part, $31 million multicenter study, UF physicians will give insulin capsules to relatives of people with diabetes, who have a 20 percent to 50 percent risk of developing the disease in the next five years. Participants will be divided into two groups: one will receive oral insulin, the other, a “placebo,” which is a capsule containing no active ingredient.

  • About 60,000 Americans will be screened to find 500 patients, ages 3 to 45, who will be followed for five years. The national trial is funded by the National Institutes of Health, the Juvenile Diabetes Foundation, the American Diabetes Foundation and Eli Lilly & Co.
    UF researchers also are involved in the first part of the trial, which entails giving daily insulin injections to relatives of people with diabetes in an attempt to hold the disease at bay. These relatives have a greater than 50 percent risk of developing diabetes during the next five years. This trial involves hundreds of medical centers and physician practices throughout the United States.

  • The second study, sponsored by Eli Lilly, involves 300 patients, ages 5 to 60, who are newly diagnosed with diabetes but have not been treated with insulin injections for more than six weeks. More than 3,000 prospective participants will be screened. Those who are selected will receive oral insulin. Researchers will focus more on adults, not children, in this study.

Researchers hope their efforts will enable people to avoid the need for insulin injections, said principal investigator Dr. Noel Maclaren, professor and chairman of pathology at UF’s College of Medicine, and an internationally recognized diabetes authority.
“In mice bred to develop diabetes, feeding insulin from early life delays the disease significantly,” Maclaren said. “We hope humans will behave the same way — that by giving insulin by mouth we will be able to halt or delay the body’s attack on the insulin-producing cells in the pancreas, and prevent or delay the need for injectable insulin therapy. The premise is that by giving insulin orally we may be able to alert the immune system that it is about to encounter something beneficial, like food, and thereby suppress an immune response that is harmful.

“However, taking insulin by mouth is not a substitute for diabetics who already are taking shots,” he cautioned. “It won’t work for people whose bodies no longer manufacture insulin. They need shots or they will get very sick and could even die from their disease. It is not a new way of taking insulin replacement, but may be a way of interrupting the process that causes diabetes.”

Insulin-dependent diabetes occurs when white blood cells vital to the

body’s defenses against infectious diseases launch a self-directed or “autoimmune” attack on the insulin-producing beta cells in the pancreas. The insulin produced by these beta cells regulates how body cells use and store sugar and other food nutrients for energy.

This insidious attack, thought to occur in individuals who are genetically predisposed, can continue for months to years before enough beta cells are destroyed that diabetes results.

Research has shown that more than half of the pancreas’ insulin-producing beta cells must be irreversibly destroyed before an individual develops symptoms.

Physicians can now detect the autoimmune attack that leads to diabetes by searching the blood for specific antibodies (disease fighting proteins), which signal that insulin-secreting beta cells are being destroyed.

An important antibody, islet cell autoantibodies (ICA), will be present in 3 percent to 4 percent of relatives of people with Type I diabetes and 10 percent to 15 percent of newly diagnosed adults with diabetes. These ICA react to several proteins within islet cells, known as GAD, IA-2 and IA-2b, all of which can be separately detected.