LOS ANGELES — Type 2 diabetes, like Type 1, may be an autoimmune disease, but the immune system’s target cells are different, Stanford University researchers said Sunday. The discovery sheds light on how obesity contributes to the onset of Type 2 diabetes and could lead to new types of treatment, 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 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 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. In studies of mice and a group of obese men with and without diabetes, they found that the diabetic men had a distinct group of antibodies against cellular proteins that were not present in the healthy men, suggesting that an unusual autoimmune reaction was taking place. The findings suggest that some people are genetically more susceptible to the immune reaction, which is typical of autoimmune diseases.
“We are in the process of redefining one of the most common diseases in America as an autoimmune disease, rather than a purely metabolic disease,” Daniel Winer said in a statement. “This work will change the way people think about obesity, and will likely impact medicine for years to come as physicians begin to switch their focus to immune-modulating treatments for Type 2 diabetes.”
