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Insulin Identified as Trigger for Causing Type 1 Diabetes

Jun 7, 2005

Insulin, the hormone most closely linked to diabetes, has turned out to be the cause of the inherited form of the blood sugar disease. For reasons that remain unclear, in patients with type 1 diabetes the body’s immune T-cells react against insulin-producing cells in the pancreas — effectively shutting them down and triggering disease onset.

After eight long years of painstaking research, scientists believe they’ve finally pegged insulin as the prime antigen — immune system target — responsible for this shutdown. "In the end, it’s a very simple answer. A lot of studies that we do in science tend to be complex, but in this case, we get a break," said lead researcher Dr. David A. Hafler, Breakstone professor of neurology at Harvard Medical School. Buoyed by the findings, researchers elsewhere are already hard at work testing out insulin as the basis of a possible vaccine against type 1 diabetes.

Scientists have long known that type 1 diabetes is caused by the body’s immune system turning against cells in the pancreas that produce insulin. What’s remained unclear is the target for this immune response.

"Of course, it’s been such an obvious question — what’s the antigen?"

Unfortunately, the only way to adequately answer that question in humans is to examine tough-to-obtain pancreatic lymph tissues. "It took us years to get these tissues, to clone the cells and then to really characterize them and examine their activity," he said. That effort has paid off, however: Supported by evidence from other, smaller papers, the Nature study "really weaves a rather compelling story that indeed the target — the cause — of type 1 diabetes may be T-cell reactivity to insulin," Hafler said.
"I think this really clinches it, in my view," said Dr. Jay Skyler, associate director of the University of Miami’s Diabetes Research Institute. "The study provides the last bit of evidence in humans; it’s really very important," he added. "It resolves a controversy because, based on animal models, there had been considerable debate as to whether the primary antigen for type 1 diabetes is insulin or [a second compound] glutamic acid decarboxylase (GAD)," Skyler said. "That controversy has been going on for 15 years."

While GAD might still play some role in type 1 disease, Hafler’s group seems to have proven that insulin is the real culprit, Skyler said.

Long before this week’s announcement, his team in Miami was already hard at work testing insulin as a potential basis for a vaccine against type 1 disease. "We screened 103,000 relatives of people with type 1 diabetes to pick out people at risk," Skyler explained. "Then we gave them either injected or oral insulin as a potential vaccine."

The hope is that introducing insulin to individuals at high risk for type 1 diabetes might desensitize their immune systems to the hormone, thereby preventing the disease. The injection-based trial largely failed, Skyler noted, perhaps because safety concerns limited the dose researchers could administer.

"But in the oral trial, we actually have a subgroup where it appears to have a beneficial effect. We’re going to do further studies on that, to clarify it," Skyler said.

Nature, May 12, 2005


DID YOU KNOW: 75% of Type 2’s do not know their A1c number. Explain to them what their number means by converting the A1c number into a number they can understand like a 6%A1c is equal to them having a BG reading of 135mg/dL every second of the day for the last 90 days. If they are only checking their fasting readings, they will see that it is much higher then what they thought it was.