Causes of Type 1 Diabetes

In the United States, there are approximately 1 million people with type 1 diabetes, and about thirty thousand new cases are diagnosed each year. Type 1 diabetes can occur at any age and in any ethnicity, but is more common in children and young adults of Caucasian ancestry. Most cases occur in families where there is no history of diabetes, but when you have a family member with diabetes, your risk of getting the disease is higher. Over the past forty years, there has been an increase in the incidence of type 1 diabetes in many countries, and it is occurring in younger children. For example, we have good data for Finland: in 1953, the incidence of diabetes was twelve people per one hundred thousand. In 1996, the incidence had increased to forty-five people per one hundred thousand.

In type 1 diabetes, we know a fair bit about the genes, but relatively little about how environmental factors impact the disease. Type 1 diabetes occurs when the immune system that normally protects the body against infections goes wrong and attacks the beta cells that make insulin. There are genetic factors and environmental factors that cause the immune system to do this.

Genetics

Scientists have identified a number of genes that increase an individual's risk for developing type 1 diabetes. The genes that are particularly important include the following:

·Several genes located in a region of the human genome called human leukocyte antigen (HLA). Two of the genes (called DR and DQ) code for proteins that help the immune system recognize foreign proteins such as those that make up viruses and bacteria. There are many forms of these two genes, and the ones that increase the individual's susceptibility to type 1 diabetes are called DR3.DQ2 and DR4.DQ8.

·The insulin gene. It has been shown that insulin teaches the immune system not to react against the beta cells-This teaching process is referred to as inducing tolerance. People with diabetes are more likely to have a form of the insulin gene that is less effective in maintaining tolerance.

These genetic factors explain why the risk of diabetes is increased if you have a family member with the disease. If you have a family member with diabetes, your risk is 5 to 6 percent, compared to the risk in the general population, which is 0.4 percent. In identical twins this risk increases to 30 to 40 percent.

Environment

The environment plays a big role in the development of type 1 diabetes-In fact it's twice as important as the genes. The evidence for this comes from several different observations:

·First, for the past forty years, the incidence of diabetes has been increasing, and it is occurring in younger children. This time period is too short for this to be a change in the genetic makeup of the population.

·Second, diabetes is more common in the northern latitudes (Scandinavia) and becomes less frequent as you go toward the equator.

This is not because people at the equator are genetically protected-when they migrate to northern latitudes, they too become susceptible to type 1 diabetes. For example, it was recently shown that Pakistani children born and raised in England have a higher risk for developing type 1 diabetes compared to children who have lived in Pakistan all their lives.

What is it in the environment that increases the risk of getting type 1 diabetes? We do not know. However, there have been a number of hypotheses: one hypothesis relates type 1 diabetes to infections with viruses such as rubella and Coxsackie B4; another hypothesis relates type 1 diabetes to the consumption of cow's milk. So far, neither of these has been confirmed as being the culprit.

One reason it is hard to figure out which environmental factor is important is that the factor may be important for initiating the autoimmune process, but not for maintaining it. Since the immune attack starts many years before a person develops diabetes, it is difficult to figure out what environmental factor was present right at the beginning when the autoimmune process first started. There has been a suggestion that in the developed countries, a lack of childhood infections means that the immune system does not develop properly, and this leads to autoimmunity and the development of conditions such as asthma and diabetes. This theory is known as the hygiene hypothesis