Scientists at the National Institutes of Health have identified a protein that is an important marker for type I (insulin dependent) diabetes. The protein can be used in combination with two other known marker proteins to improve diagnosis of individuals who have diabetes, and identify those at risk of developing the disease. It and other marker proteins are candidates for experimental treatments aimed at preventing the onset of type I diabetes.

The identification of the new marker protein, as reported in the "Procedings of the National Academy of Sciences", is part of an ongoing study at the National Institute of Dental Research. Scientists at NIDR's Laboratory of Oral Medicine are investigating the molecular biology of diabetes, a condition which, on top of the risk of heart, kidney, and eye complications, is known to increase risk of gum disease and tooth loss.

IDDM, type I diabetes, is an autoimmune disease in which the immune system produces antibodies that attack the body's own insulin-manufacturing cells in the pancreas. These antibodies, called autoantibodies, form the basis of the existing diagnostic test for IDDM. In this test patient serum reacts with sections of human pancreas tissue, a labor-intensive procedure. Recently, however, scientists have been able to identify some of the target proteins (that react with the antibodies) in the pancreas, and are using this knowledge to improve detection of diabetes and streamline the screening process.

Doctors Michael Lan and Abner Notkins have now identified two protein markers, IA-1, and IA-2, and cloned and sequenced the genes for both. Genetically engineered versions of both have been produced in the laboratory. The two markers, when used in diagnostic tests, "recognized" antibodies in 70% of IDDM patients. Combining them with a third marker, a protein called GAD-65, increased the recognition rate to 90% in persons with IDDM. Furthermore, the presence of autoantibodies to the marker proteins in otherwise normal individuals was highly predictive in identifying those at risk of ultimately developing clinical symptoms of the disease.

"The identification and production of these markers makes it possible to develop a rapid and effective test to screen large populations for IDDM," says Dr. Notkins. "In addition, the proteins are candidates for immune tolerance studies, which attempt to prevent the development of destructive antibodies and subsequent disease."

Persons without diabetes also have the marker proteins on their beta cells, but do not make antibodies. The scientists are hopeful their research will aid in uncovering the actual cause of type I diabetes.