Causes of Type 1 Diabetes

Insulin is produced by the beta cells in the pancreas. In people with type 1 diabetes, the immune system mistakenly destroys these cells. The body responds to the beta cells as if they were foreign invaders.  This is called an autoimmune response.

Autoimmune responses also occur in other diseases such as multiple sclerosis, lupus, and thyroid diseases such as hypothyroidism (Hashimoto’s disease) and hyperthyroidism (Graves’ disease). Researchers do not know exactly why this happens.

But for diabetes, researchers have found many factors that appear to be linked to type 1 diabetes. These include genetics, autoantibodies, viruses, cow’s milk, and oxygen free radicals.

Scientists have long suspected that genetics play a role in type 1 diabetes.  If your mother or father had diabetes,  for example, you are more likely to develop the disease than someone without a family history. Also, type 1 diabetes seems to be more common in certain racial groups. Caucasians, for example, are more likely to develop the disease than are people from other racial backgrounds. Type 1 diabetes occurs in less than 1 of 100,000 people in Shanghai, China, but occurs in more than 35 of 100,000 people in Finland.

Everyone is born with a set of instructions that tells the cells in your body how to grow, live, and function. These instructions lie in the particular chemical sequence of units known as bases, which make up the DNA in every cell in your body. Each cell in your body contains 46 chromosomes,  which are made up of DNA and protein. Each DNA strand is like a long string that contains millions of bases. Along the strand lie the genes, unique segments of DNA that tell your cells what kind of protein to make.

But just as books sometimes contain typographical errors, so too does the sequence of DNA. If there is a mistake, or mutation, in the DNA within a gene, then a faulty protein may be made that can’t do its job. Scientists are trying to determine how mistakes in specific genes cause diabetes. If mutated genes occur in germ cells-the eggs and sperm-then the DNA mutations can be passed on from generation to generation.

Researchers have identified several different genes that might make a person more likely to develop type 1 diabetes. However, they have not found one single gene that makes all people who inherit it develop the disease. Instead, it seems that there are several genes known as “diabetes susceptibility” genes.

One particular set of genes that may predispose a person to diabetes is responsible for a set of proteins known as the human leukocyte antigens, or HLAs. These genes code for certain proteins called antigens, which identify a person’s own cells as “self.” They tell the immune cells not to destroy the cells that are part of a person’s body. Scientists believe that some HLAs incorrectly tag a person’s own beta cells as “non-self.” Then the immune cells,  which normally destroy foreign invading cells,  destroy these cells.  This is called autoimmunity-an immune attack on a person’s own cells. In type 1 diabetes, the beta cells of the pancreas are destroyed in an autoimmune attack, and the body can no longer make insulin. This destructive process occurs over many months or years.

Each person has many kinds of HLA genes, and thus there are many types of HLAs. Each person inherits one of each kind of HLA gene from each parent. One type of HLA gene, known as HLA-DR, is most strongly linked to type 1 diabetes. There are many variations of HLA-DR, but 95 percent of people with type 1 diabetes have the DR3 form, the DR4 form, or both.

This makes researchers suspect that having the DR3 and DR4 variants may make a person more likely to get type 1 diabetes.

However, this is not the whole answer, because 45 percent of people without type 1 diabetes have the DR3 or DR4 variants.

Also, variants of another HLA gene, known as HLA-DQ, may also play a role in type 1 diabetes.

Just because a person inherits a susceptible HLA variant doesn’t mean that person will develop diabetes. Most people with DR3 or DR4 variants remain healthy. But if there is a family history of type 1 diabetes, then screening may help predict the risk of developing the disease. For example, brothers and sisters of a person with diabetes who have two of the same HLA-DR variants have a 15 percent chance of getting type 1 diabetes. But if they share only one variant, the risk is only 5 percent. If no variants are the same, the risk of developing type 1 diabetes is 1 percent or less.

The more we study how people get type 1 diabetes, the more we understand that the answers are not simple. No one event or characteristic seems to bring on diabetes. Researchers have identified several other gene clusters on different chromosomes in addition to these HLA variants that may also play a role in type 1 diabetes.

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