Insulin - possible vaccine against type 1 diabetes

May 11 2005

It has taken scientists at the University of Miami's Diabetes Research Institute eight long years of painstaking research, but they believe they have finally pinned down Insulin, the hormone most closely linked to diabetes, to be the cause of the inherited form of the blood sugar disease.

The body's immune T-cells, for reasons that remain unclear, in patients with type 1 diabetes, react against insulin-producing cells in the pancreas shutting them down, which triggers the onset of the disease. The researchers believe that insulin is the prime antigen, immune system target, responsible for this shutdown.

Lead researcher Dr. David A. Hafler, Breakstone professor of neurology at Harvard Medical School says in the end, it was a very simple answer.

He says many studies done in science are complex, but in this case, they had a breakthrough.

Motivated by the findings, other researchers are already testing out insulin as the basis of a possible vaccine against type 1 diabetes.

According to the American Diabetes Association almost 16 million diabetic Americans have the type 1 form of the disease, the vast majority of diabetics suffer from type 2 diabetes, where other factors such as increasing weight gain gradually desensitize the body's cells to the effects of insulin.

Scientists already knew that type 1 diabetes is caused by the body's immune system turning against cells in the pancreas that produce insulin, but were unclear what the target for this immune response was. Hafler says it now seems that questioning ' what is the antigen', is such an obvious question.

He says the only way to properly answer that question in humans is to examine almost inaccessible pancreatic lymph tissues, which took them years to get, to clone the cells and then to characterize them and examine their activity. But the effort paid off, and is supported by evidence from other studies.

Dr. Jay Skyler, associate director of the Diabetes Research Institute says in his view the study provides the last piece of evidence in humans and is really very important.

He says it resolves a controversy which has been going on for 15 years because, based on animal models, there had been considerable debate as to whether the primary antigen for type 1 diabetes is insulin or glutamic acid decarboxylase (GAD), which though it might still play some role in type 1 disease, insulin appears to be the real culprit.

His team in Miami are already hard at work testing insulin as a potential basis for a vaccine against type 1 disease. 103,000 relatives of people with type 1 diabetes have been screened to pick out people at risk, they were then either injected or given oral insulin as a potential vaccine.

The team hope that by introducing insulin to individuals at high risk for type 1 diabetes it might desensitize their immune systems to the hormone, and prevent the disease.

The injection-based trial largely failed, possibly because safety concerns limited the dose researchers could administer, but in the oral trial, they have a subgroup where it appears to have had a beneficial effect. Further studies will clarify this says Skyler.

Edwin Gale, professor of diabetic medicine and head of the department of clinical science at the University of Bristol in England, cautions that a potent vaccine against the illness remains a distant goal. She says poor outcome of the Miami trials shows that the problems may have been underestimated.

Hafler does admit that while his findings are important to patients with type 1 diabetes, they have little significance for individuals with type 2, adult-onset diabetes, which he says is a totally different disease, ' the end result is the same, but the underlying cause is very different'.

The research appears in the May 12 issue of Nature.