Of Diabetes Genes and Environment

Diabetes occurs as an interaction between the genes that you inherit and the environment in which you live. In type 1 diabetes, we know a fair bit about the genes, but relatively little about how environmental factors impact the disease. In contrast, for type 2 diabetes, the genetic causes are largely unknown, but we know that obesity and lack of exercise are important environmental risk factors.

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

Causes 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 type 1 diabetes, but when you have a family member with type 1 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.

WHAT CAUSES TYPE 1 DIABETES?

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.

Type 1 Diabetes and 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 type 1 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 type 1 diabetes is increased if you have a family member with the disease. If you have a family member with type 1 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. Table 2-1 summarizes the risk if a family member has type 1 diabetes:

Table 2-1 Genetic Risk of Type 1 Diabetes Based on Family History

Family member

Relative risk of getting type 1 diabetes, %

Affected mother

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