Type 1A Diabetes develops because the body mistakenly identifies insulin-producing cells (beta cells) as being foreign, or "non-self." The immune system targets and ultimately destroys the beta cells, resulting in an absence of insulin and the subsequent diagnosis of diabetes. This autoimmune process is thought to smolder for years, and there are individuals at risk of developing diabetes who do not yet have the diagnosis.
During the "prodrome," or prior to the time of diagnosis, it is speculated that the regulatory T cells are unable to control cytotoxic T cells directed against self-proteins.
CD4 and CD8 T cells coordinate to attack and destroy insulin-producing cells (beta cells). At the same time, B cells are making antibodies against beta cell proteins.
There may be some beta cell re-formation (by cell division or by new cell formation) that replaces the destroyed cells. But over the years, the net destruction is greater than the replacement. When the number of beta cells is reduced by approximately 80%, the body is unable to secrete enough insulin, the blood glucose rises and clinical Diabetes is diagnosed. The diagnosis of Diabetes is based on an elevated blood glucose.
The prolonged development period prior to the diagnosis of Diabetes has several implications:
- At-risk individuals may be identified.
- At-risk individuals will still have significant beta cell function.
- What is happening in the autoimmune process on a cellular and molecular basis can be studied.
- If we know how to interrupt or stop the process, we may be able to delay and prevent progression to Diabetes.
Read more about Type 1 Diabetes research
Who is at risk?
Type 1 Diabetes is diagnosed worldwide, and occurs in every race and nationality.
The incidence (or frequency) of the disorder is increasing in every population. Type 1 Diabetes is most common in white people or individuals of Northern European heritage, in whom the incidence is 1 out of every 300 or 400 individuals. Finland and Sardinia are "hot spots" where the risk of Type 1 Diabetes is 1 out of every 100 to 200 people.
The reasons for the geographical and racial differences are not understood. The presence of antibodies directed against beta cell antigens or molecules is a significant risk factor for the development of Type 1 Diabetes. The antibodies are directed against proteins associated with the beta cells, such as glutamic acid decarboxylase, tyrosine phosphatase, insulin and heat shock proteins.
Commercial tests are available for:
- glutamic acid decarboxylase (GADAs)
- islet cell antigen 512 (ICA512s or ICA IA-2s)
- insulin auto-antibodies (IAAs)
- islet cell antibodies (ICAs)
- zinc transporter 8 (ZnT8)
Up to 3-5% of the general population may test positive for one of these antibodies, but only about 20% of these individuals will develop diabetes. The presence of two antibodies, however, creates a more than 75% risk of developing Type 1 Diabetes within the next 10 years. Among identical twins, if one twin has Type 1 Diabetes there is a 40% chance that the other twin will also develop Type 1 Diabetes. Recent research suggests that the number may be much higher. And if one identical twin is positive for antibodies directed against the beta cell, and the other has Type 1 Diabetes, it is almost certain that both will eventually have Diabetes.
A predictive test used in research – the intravenous glucose tolerance test:
Another predictive test, called an intravenous glucose tolerance test (IVGTT), evaluates "first phase" insulin secretion. "First phase" refers to the amount of insulin secreted within the first few minutes after the administration of the intravenous glucose. When someone has a low first phase insulin secretion and two or more antibody tests are positive, there is at least a 90% risk of developing clinical Diabetes within the next few years.