Discovery May Aid Detection of Diabetes : Science: Antibodies to protein identified by researchers are present in the bloodstream as long as seven years before disease develops.

A major step toward the identification of individuals likely to develop insulin-dependent diabetes is reported today by researchers from UC San Francisco and Yale University. Physicians hope that earlier detection of potential diabetics will allow intervention and prevent development of the disease.

The research team has identified a protein in the pancreas that is destroyed by an individual’s immune system, thereby causing the disease, according to a report in the British journal Nature. Antibodies to this protein are present in the bloodstream as long as seven years before diabetes develops, making it possible to identify individuals who are almost certain to develop the disease.

“This is a big deal . . . a very exciting piece of news,” said pathologist Noel Maclaren of the University of Florida.

Researchers have recently begun clinical trials using drugs such as azathioprine to suppress the so-called autoimmune attack in such individuals, hoping to forestall the onset of diabetes and give the patients at least several additional years without the need for daily injections of insulin.

Physicians are now using relatively crude tests for antibodies against insulin to identify individuals who will receive the treatment, but such procedures miss many potential victims.

Tests for antibodies against the newly identified protein, which should be available in a few months, are expected to be much more accurate in identifying potential diabetics, improving the odds that the screening process will identify all individuals likely to develop the disease.

Identification of the protein may also make possible other ways to interfere with the autoimmune attack, such as by selectively destroying antibodies directed against it.

“This really puts out hope for us being able to come to terms with the immune response that leads to diabetes,” said Robert E. Silverman, head of the diabetes branch at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md. “It’s pregnant with possibilities for potential breakthroughs.”

Between 750,000 and 1 million Americans suffer from insulin-dependent diabetes, also known as juvenile-onset or Type 1 diabetes, according to the American Diabetic Assn., and 13,000 to 15,000 new cases are diagnosed each year.

Although insulin injections can control the overt symptoms--such as excessive thirst and urination--that can lead to coma, most diabetics eventually develop serious complications, including kidney damage, nerve damage in the arms and legs and vision loss. By preventing, or at least delaying, the onset of the disease with the immune-suppressing drug, researchers hope to reduce the severity of these complications.

Researchers have known about the newly identified protein, which has been called the 64K protein because of its size, for several years. Researchers around the world have been trying to isolate and purify the protein, but this has been extremely difficult because it occurs in very low quantities in the pancreas.

The breakthrough came from an unexpected source. Biologist Pietro De Camilli, now at Yale in New Haven, Conn., and formerly at the University of Milan in Italy, has been studying a seemingly unrelated autoimmune disorder called “stiff-man syndrome.” That very rare disease of the central nervous system, which affects perhaps only 300 people worldwide, is characterized by progressive rigidity and painful spasms of muscles throughout the body.

The Yale team reported in May that patients with stiff-man syndrome showed very high concentrations of antibodies against an enzyme called glutamic acid decarboxylase (GAD), which plays a vital role in brain cells that are important in muscle activity.

Three key factors led to the conclusion that GAD was the 64K protein. First, as many as 20% of the individuals with stiff-man syndrome were also diabetic, De Camilli discovered, a much higher percentage than in the population at large.

Second, GAD is also found in the insulin-secreting cells of the pancreas. “That is practically the only place outside the nervous system where there is a significant concentration of the enzyme,” De Camilli said in an interview.

And third, GAD is the same size as the 64K protein.

Based on these factors, De Camilli contacted immunologist Steinunn Baekkeskov of UC San Francisco, who was attempting to isolate the 64K protein. “The collaboration very quickly resulted in the demonstration that the two proteins were the same,” he said.