For the first time, researchers are closing in on ways to prevent or at least limit the devastating effects of type 1 diabetes.

By using new treatments, including drugs normally given to organ-transplant patients, doctors hope to stem the progress of the disease -- in which the body's own immune system destroys its ability to produce insulin, leading to serious and potentially fatal complications. If proven effective, the new therapies could offer one of the first major advances in treatment since injectable insulin was first made available in 1922, researchers say.

At least one million adults and children in the U.S. suffer from type 1 diabetes, an autoimmune disease also known as juvenile diabetes because it typically strikes between the ages of 10 and 14. Type 1 diabetes is very different from the more-prevalent type 2 diabetes, which is often linked to obesity. People with type 2 diabetes can't use the insulin they do produce, or they don't produce enough. Insulin is a hormone needed to convert food into body fuel, and without it, blood-sugar levels soar.

While type 2 diabetes can often be managed with diet and exercise, there has been little that endocrinologists have been able to do to stem the progression of type 1. The immune systems of type 1 diabetics gradually kill off insulin-producing cells in the pancreas, leaving patients far more vulnerable to complications, ranging from fainting to blindness, heart disease and loss of limbs. The disease is fatal without regular injections of artificial insulin.

Doctors have tried immunosuppressant drugs to slow type 1 diabetes, but the treatments were too toxic for patients to use long term. Now, the development of less-harmful drugs has helped prompt immunologists and endocrinologists to again try treatments that affect the immune system. In addition to testing drugs that keep transplant recipients from rejecting new organs, they are studying therapies used for other autoimmune diseases such as rheumatoid arthritis, and new uses for insulin itself.

Researchers believe that giving these treatments early on, before the disease can shut down insulin production, may eventually prevent the disease in people who are at risk -- such as those with a family history. Or it may lessen the effects of type 1 diabetes in those who have recently developed it. Patients may not be cured, but they would be much better able to regulate their blood sugar and thus less at risk for complications.

"We're talking about changing the fundamental course of this disease," says Kevan Herold, associate professor of clinical medicine at Columbia University, who is leading some of the new research. A number of diabetes centers across North America, Europe, Australia and New Zealand are participating in clinical trials of the treatments.

In one clinical trial, conducted by an international network of researchers known as Type 1 Diabetes Trialnet, patients diagnosed with diabetes within the past three months are given two immunosuppressant drugs: Mycophenolate mofetil, or MMF, and Daclizumab, or DZB, from Roche Holding AG. The hope is that the drugs will prevent diabetics' immune systems from attacking and killing insulin-producing beta cells in the pancreas, just as they prevent a transplant patient from rejecting a new heart or kidney. Trialnet is funded by the National Institutes of Health and diabetes groups such as the Juvenile Diabetes Research Foundation.

Two other trials, offered by Trialnet and another group known as the Immune Tolerance Network, will test antibodies known to block parts of the immune cells responsible for attacking insulin-producing cells. One of the antibodies, known as anti-CD3, appeared to halt the destruction of insulin-producing cells in an initial study with a small number of new-onset patients, says Jeffrey Bluestone, an author of that study and director of the Immune Tolerance Network, funded by the NIH and diabetes groups. The other antibody, anti-CD20, is also known as Rituxan, a drug co-marketed by Genentech Inc. and Biogen Idec Inc. for rheumatoid arthritis, cancer and other diseases.

The new tests can be arduous and time-consuming, particularly for children, who make up the bulk of recently diagnosed patients. Participants in the Trialnet MMF/DZB trial must undergo extensive blood tests, two intravenous injections of medication in the first month, and then take pills two or three times a day for two years. They travel sometimes hundreds or even thousands of miles for regular visits to the clinic overseeing the trials.

"It's a great challenge to enroll people," acknowledges Desmond Schatz, associate chairman of pediatrics and medical director of the Diabetes Center at the University of Florida in Gainesville, Fla., who is helping conduct some of the studies. The task is particularly difficult for a new diabetic, who is adjusting to frequent blood-sugar checks and insulin injections, he says.

Moreover, most of the trials are limited to children age 8 or older; some, like the MMF/DZB study, won't enroll anyone under 12 years of age. One reason: The immunosuppressant drugs leave the immune system less primed to fight off infections. And there is no guarantee of a benefit, because a portion of participants end up in control groups, which take only placebo medications.

Still, Ana Paredes, a pediatric nephrologist in Miami, says enrolling her son, Alejandro Perez, in the MMF/DZB trial has been worth it. When he was diagnosed in October 2004 at the age of 13, she and her husband made the six-hour drive to Gainesville to enroll him. More than a year later, "he's doing great," she says.

Dr. Paredes wasn't told whether Alejandro is getting the real medications or a placebo, and she worries about how he will fare once the treatment period ends. Regardless, though, she says he has benefited from close monitoring and checkups from the doctors. "It's been a tremendous educational experience, and we're getting good medical advice," she says.

A number of studies plan to probe whether doses of insulin itself can prevent the onset of type 1 diabetes by toughening regulatory cells in the immune system so that they keep the destructive cells that trigger diabetes in check. A trial under way in Finland, and another scheduled to begin in Australia in April, will study the effect of daily doses of insulin administered nasally to children who are deemed to be at risk of developing diabetes. Scientists determine who is at risk with a special blood test to detect autoantibodies that indicate the immune system may already be attacking insulin-producing cells.

Another trial, which researchers hope to start in June in the U.S. and four other countries, will offer insulin capsules to relatives of diabetics between the ages of three and 45 who are at risk of developing the disease themselves. Doctors don't know exactly what causes diabetes, but it is believed to be a combination of genetic and environmental factors. A preliminary study of 372 people showed that taking insulin delayed the onset of diabetes for 4.5 years, says Jay Skyler, an endocrinologist at the University of Miami and director of Trialnet, which will conduct the test.

Other planned clinical trials include trying a Genzyme Corp. immunosuppressant drug called thymoglobulin, and a treatment for prediabetics using the anti-CD3 antibody and another drug.

The Latest Fronts

Some treatments being studied to prevent or slow the progression of type 1 diabetes:

Immunosuppressant drugs MMF/DZB, normally given to organ-transplant patients.

An antibody known as anti-CD3 that blocks some parts of the immune system.

Rituximab, an antibody also known as anti-CD20 that destroys a part of the immune system implicated in diabetes.

Insulin -- the hormone that type 1 diabetics lose the ability to produce.