Type 2 diabetes, like Type 1, may be an autoimmune disease, researchers say

Type 2 diabetes, like Type 1, may be an autoimmune disease, but the immune system's target cells are different, Stanford researchers said Sunday. The discovery sheds new light on how obesity contributes to the onset of Type 2 diabetes and could lead to new types of treatment for the disorder, the researchers reported in the journal Nature Medicine.

Diabetes is a growing problem in the United States, triggered in large part by the obesity epidemic. An estimated 27 million Americans are now thought to have diabetes, with the vast majority of them -- all but about a million -- afflicted with Type 2 diabetes. That disorder strikes in adulthood and is marked by a growing inability of cells to respond to insulin in the bloodstream, which necessitates using drugs to increase the output of the hormone by the pancreas. Intriguingly, not everyone who becomes obese develops diabetes, however, and researchers have never been sure why.

Dr. Daniel Winer, an endocrine pathologist now at the University of Toronto, and his twin, Dr. Shawn Winer of the University of Toronto's Hospital for Sick Children, reasoned that the death of excess fat cells might trigger an autoimmune reaction. In an earlier study with senior author Dr. Edgar Engleman of the Stanford University School of Medicine, they demonstrated in mice that, as fat accumulates in the tissues surrounding organs, it outstrips its blood supply, leading to the death of cells on the periphery of the fat deposits. When that occurs, the body mobilizes its immune system to break down and carry off the dead cells. But that produces antibodies against the cells and many of the proteins normally found only inside the cells.

In the new study, the team turned its attention to B cells, the lymphocytes or white blood cells that manufacture antibodies against foreign invaders. They genetically engineered mice so that they could not produce B cells and found that the rodents never became diabetic, no matter how fat they became. They next looked at normal mice that were prone to becoming diabetic when they became obese. One group they treated with a biological drug called anti-CD20 that binds to B cells and blocks their activity. The second group received no treatment. The mice that received the drug did not become diabetic when they became obese, while those that did not receive it did become diabetic. The effect lasted only about 40 days, however, and then needed to be repeated...