The development of insulin resistance that leads to type 2 diabetes could be due to an immune system reaction. New research has identified immune system antibodies among obese people who are insulin-resistant that are not found in people lacking insulin resistance. The findings of the study were recently published online in the journal Nature Medicine.
According to study co-author Dr. Daniel Winer, an endocrine pathologist at the University Health Network of the University of Toronto in Ontario, Canada, “We are in the process of redefining one of the most common diseases in American as an autoimmune disease, rather than a purely metabolic disease.” He went on to explain, “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.”
Winer, along with his twin brother, Shawn Winer, of the Hospital for Sick Children at the University of Toronto, and Stanford research associate Lei Shen are co-first authors of the study. Winer was a postdoctoral fellow at Stanford University in California when the research began. Edgar Engleman, a Stanford pathology professor, and director of Stanford’s Blood Center, is the senior author of the study.
Almost 26 million Americans suffer from diabetes, according to the U.S. Centers for Disease Control and Prevention. The vast majority of cases (90 to 95 percent) are type 2 diabetes. With type 2 diabetes, the body either does not produce enough insulin, or the boy’s cells ignore the insulin. The body needs insulin in order to use glucose for energy. When food is consumed, sugars and starches are broken down into glucose to fuel the body’s cells, and insulin transfers it from the blood into the cells. A build up of glucose in the blood that is not taken to the cells leads to diabetes complications. In Type 1 diabetes, defined as an autoimmune disease, the body fails to produce insulin due to destruction of the insulin-producing beta cells in the pancreas by the immune system.
For their study, the researchers tested blood samples from 32 obese males, among whom half had insulin resistance. Only those who were insulin-resistant were found to have a distinct set of antibodies when compared to those who were not insulin-resistant. According to Winer, because those who were not insulin-resistant appear to have protective antibodies, it may be possible to develop a vaccine for type 2 diabetes.
The researchers believe that insulin resistance may result from immune system B cells and other immune cells attacking the body's own tissues. Instead of creating antibodies against a foreign substance to protect the body, the B cells create antibodies against fat cells. These antibodies begin attacking the fat cells, making them insulin resistant and thwarting their ability to process fatty acids.
As part of their study, the research team was able to show that an antibody called anti-CD20, known to target and eliminate mature B cells in the immune system, halted the development of type 2 diabetes among male lab mice prone to developing the disease, and brought their blood sugar to a normal level. Although anti-CD20 is already available in the US under the trade names Rituxan and MabThera, and is already approved for the treatment of certain autoimmune diseases and blood cancers, more research will be required to determine its affectiveness against diabetes in humans.
Winer pointed out the both the mice and the humans in the study were male. Therefore, it remains unclear whether the study findings are applicable to women. He also noted that anti-CD20 is not benign, as it dampens the immune system and may cause adverse effects.
It has long been know that type 2 diabetes runs in families, indicating the possibility of a genetic component. However, the actual cause has remained unclear. The study results lend hope for a true understanding of the disease and future success for its prevention and treament.
According to study co-author Dr. Daniel Winer, an endocrine pathologist at the University Health Network of the University of Toronto in Ontario, Canada, “We are in the process of redefining one of the most common diseases in American as an autoimmune disease, rather than a purely metabolic disease.” He went on to explain, “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.”
Winer, along with his twin brother, Shawn Winer, of the Hospital for Sick Children at the University of Toronto, and Stanford research associate Lei Shen are co-first authors of the study. Winer was a postdoctoral fellow at Stanford University in California when the research began. Edgar Engleman, a Stanford pathology professor, and director of Stanford’s Blood Center, is the senior author of the study.
Almost 26 million Americans suffer from diabetes, according to the U.S. Centers for Disease Control and Prevention. The vast majority of cases (90 to 95 percent) are type 2 diabetes. With type 2 diabetes, the body either does not produce enough insulin, or the boy’s cells ignore the insulin. The body needs insulin in order to use glucose for energy. When food is consumed, sugars and starches are broken down into glucose to fuel the body’s cells, and insulin transfers it from the blood into the cells. A build up of glucose in the blood that is not taken to the cells leads to diabetes complications. In Type 1 diabetes, defined as an autoimmune disease, the body fails to produce insulin due to destruction of the insulin-producing beta cells in the pancreas by the immune system.
For their study, the researchers tested blood samples from 32 obese males, among whom half had insulin resistance. Only those who were insulin-resistant were found to have a distinct set of antibodies when compared to those who were not insulin-resistant. According to Winer, because those who were not insulin-resistant appear to have protective antibodies, it may be possible to develop a vaccine for type 2 diabetes.
The researchers believe that insulin resistance may result from immune system B cells and other immune cells attacking the body's own tissues. Instead of creating antibodies against a foreign substance to protect the body, the B cells create antibodies against fat cells. These antibodies begin attacking the fat cells, making them insulin resistant and thwarting their ability to process fatty acids.
As part of their study, the research team was able to show that an antibody called anti-CD20, known to target and eliminate mature B cells in the immune system, halted the development of type 2 diabetes among male lab mice prone to developing the disease, and brought their blood sugar to a normal level. Although anti-CD20 is already available in the US under the trade names Rituxan and MabThera, and is already approved for the treatment of certain autoimmune diseases and blood cancers, more research will be required to determine its affectiveness against diabetes in humans.
Winer pointed out the both the mice and the humans in the study were male. Therefore, it remains unclear whether the study findings are applicable to women. He also noted that anti-CD20 is not benign, as it dampens the immune system and may cause adverse effects.
It has long been know that type 2 diabetes runs in families, indicating the possibility of a genetic component. However, the actual cause has remained unclear. The study results lend hope for a true understanding of the disease and future success for its prevention and treament.
