Monday, April 29, 2019

Is Type 2 Diabetes Autoimmune?

Is type 2 diabetes as well as type 1 diabetes autoimmune?

The classic description of type 1 diabetes is that it's an autoimmune disease. Normally, control mechanisms make sure that the body doesn't attack itself, but in type 1 diabetes, something has gone wrong with this process and the immune system does attack the beta cells, eventually almost totally wiping them out, so people have to inject insulin.

Type 2 diabetes, on the other hand, is described as a disease of insulin resistance. The beta cells can still produce insulin, but not enough to overcome the insulin resistance, and as time goes on and the beta cells deteriorate, type 2 patients may need insulin as well.

But researchers at the Stanford University School of Medicine and the University of Toronto say their research suggests that type 2 diabetes is also an autoimmune disease.

This makes sense to me. I've always felt that the two types of diabetes have a similar underlying cause and secondary effects that modulate this response. Also, studies show that people with type 1 diabetes can have some insulin resistance but not usually as much as in people with type 2, and people with type 2 diabetes can produce some autoantibodies but not usually as much as people with type 1.

In other words, there may not be a sharp line between the two versions of the disease but a continuum, with some people having more of one type of defect and others more of another.

But because of the classic understanding of the two types of diabetes, doctors don't usually test for antibodies in patients with typical signs of type 2, those who are overweight and don't get much exercise, and they don't test for insulin resistance in thin patients who have autoimmune antibodies.

Of course, this new theory wouldn't mean that classic approaches to type 2 diabetes such as weight loss and increased exercise wouldn't help. When such approaches reduce insulin resistance enough, then the defective beta cells may be able to produce enough insulin to keep blood glucose normal, depending on how damaged the beta cells are by the time of diagnosis.

But if these new ideas are confirmed with more research, it would open the door to new treatments for patients with type 2, focussing on the autoimmune aspects of the disease.

The researchers say that immune cells cause inflammation in fat when the fat cells are growing so fast that new blood vessels to support the fat cells can't keep up. Some of the fat cells die as a result and spill their contents into the fat, causing inflammation. This is seen in mice on a high-fat, high-calorie diet and in humans with type 2 diabetes.

The inflammation then causes insulin resistance, according to the researchers. And mice genetically engineered so they didn't produce antibody-producing B cells did not become insulin restant when they became fat. Injecting such mice with B cells or antibodies from obese insulin-resistant mice made the mice insulin resistant. So the immune system clearly plays a role in this.

In humans, “We were able to show that people with insulin resistance make antibodies to a select group of their own proteins,” said Edgar Engleman, senior author of the paper. “In contrast, equally overweight people who are not insulin-resistant do not express these antibodies.”

This line of investigation is in early stages, but it suggests new avenues of research. And new ways of looking at a problem often lead to new solutions.

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