WHAT CAUSES TYPE 1 DIABETES?

Autoimmune Response

Type 1 diabetes is usually a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved.

Certain factors are thought to be important in this process:

• White blood cells called T lymphocytes produce immune factors called cytokines that attack and gradually destroy the beta cells of the pancreas. Important cytokines are interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma.

• Specific proteins are also critical in the process. They include glutamic acid decarboxylase (GAD), insulin, and islet cell antigens. These proteins serve as autoantigens. That is, they trigger the self-attack of the immune system on its body's own beta cells.

Progression from the first stage, known as insulitis, to full-blown diabetes can take seven years or longer. Unfortunately, by the time a person is aware that something is wrong and goes to the doctor with symptoms of type 1 diabetes, about 80% to 90% of the beta cells have been destroyed.

It should be noted that more than half of those with insulitis does not develop diabetes. Researchers are greatly interested in discovering any factors that prevent the disease. (Of considerable interest in this regard is an immune factor called interleukin 4, which may prove to be protective.)

Genetic Abnormalities

Researchers have found at least 18 genetic locations that are related to type 1 diabetes. They appear to involve abnormal interactions among normal genes, mostly those known as class I and II major histocompatibility genes, which affect the immune response.

The odds of inheriting the disease, however, are only 10% if a first degree relative has diabetes, and even in identical twins, one twin has only a 33% chance of having diabetes if the other has it. Children are more likely to inherit the disease from a father with type 1 diabetes than from a mother with the disorder.

Genetic factors cannot fully explain the development of diabetes. Over the past 30 years, a major increase in the incidence of type 1 diabetes has been reported in certain European countries, and the incidence has nearly tripled in the Northeastern US. If genetic factors were the only cause of type 1 diabetes, such an increase in cases would take at least 400 years.

Viruses

Some researchers believe one or more viral infections may trigger the disease in genetically susceptible individuals. Researchers suggest the following scenario:

• An infection introduces a viral protein that resembles a beta-cell protein.

• T cells and antibodies are tricked by this resemblance into attacking the beta protein as well as the virus.

Among the viruses under scrutiny are enteric viruses, which attack the intestinal tract. Coxsackieviruses are an enteric virus of particular interest. (One study has suggested that respiratory infection in a child's first year, and not later, may be protective against diabetes, perhaps by priming the immune response so that it is better able to respond later on to other organisms.)