Type 2 diabetes occurs when a person's tissues become progressively resistant to insulin, a hormone required for the body to metabolize dietary glucose properly. The root cause of the insulin resistance in type-2 diabetes is not known, but it's associated with obesity and can run in families. On the other hand, type 1 diabetes, an autoimmune disease, occurs when the immune system attacks and destroys insulin-producing cells in the pancreas.

     Two researchers, twin brothers Daniel Winer, M.D., of Stanford University School of Medicine, and Shawn Winer, M.D., of the Hospital for Sick Children at the University of Toronto, speculated that different types of immune cells, including T cells and B cells, can cause inflammation in the fatty tissue that surrounds and cushions organs in the body. This inflammation occurs in mice fed a high-fat, high calorie diet when the rapidly growing fat cells outstrip their blood supply and begin to die. (It's also seen in humans with type-2 diabetes). The dying cells spew their contents, and immune system cells called macrophages are summoned to clean up the mess.

     Dr. Edgar Engleman, director of Stanford's Blood Center and senior author of the research, said, "This immune reaction causes havoc in the fatty tissue, and we've found that it involves two other immune system cells--T cells and B cells--in addition to macrophages."
The resulting attack by the immune system inhibits the ability of the remaining fat cells to respond to insulin and causes fatty acids to be shed into the blood. This sets into motion a physiological process that leads to fatty liver disease, high blood pressure, and further insulin resistance throughout the body.

     The researchers turned their attention to the B cells. "The interesting thing about B cells is that, in addition to stimulating T cells, they also produce antibodies, which can have far-reaching effects," said Dr. Shawn Winer. "Antibodies are typically involved in protecting the body from infection, but they can also cause disease."

     The researchers found that mice genetically engineered to lack B cells were protected from developing insulin resistance even when they grew obese on the high-fat diet. However, injecting these mice with B cells or purified antibodies from obese, insulin-resistant mice significantly impaired their ability to metabolize glucose and caused their fasting insulin levels to increase.

     Switching the research to humans, the researchers were able to show that people with insulin resistance make antibodies to a select group of their own proteins. In contrast, equally overweight people who are not insulin-resistant do not express these antibodies.

     Dr. Daniel Winer commented, "It's highly suggestive that your body targets its own proteins as part of the development of insulin resistance. It really links the concept of insulin resistance to autoimmunity." He added, "Conversely, if we could identify a panel of antibodies that might protect against developing insulin resistance, we could begin to think about a vaccine to prevent type-2 diabetes."

--Source: Excerpted from "Type-2 diabetes linked to autoimmune reaction in study," Krista Conger, Stanford University School of Medicine, April 17, 2011