Toxic fat metabolites might cause type 2 diabetes.
Over 29 million Americans, or 9.3 percent of the United States population, live with diabetes, according to the Centers for Disease Control and Prevention (CDC). Type 2 diabetes accounts for 90-95 percent of all these cases.
Insulin is secreted by the pancreas when it detects sugar intake. Insulin enables cells to accept glucose, which is then processed by the cells and turned into energy.
In patients whose insulin is not administered effectively, glucose is not assimilated by the cells but instead builds up in the bloodstream. Diabetes occurs when levels of blood sugar are abnormally high.
Although being overweight or obese is a common risk factor for diabetes, researchers have pointed out that diabetes can still occur in people of a healthy weight.
Previous research has found that 12 percent of people diagnosed with diabetes between 1990-2011 were at normal weight. The same research indicates that once diagnosed, normal-weight participants were more likely to die from diabetes than their heavier counterparts.
Reasons for this were unknown, until now. New research may have shed light on not only why people of a healthy weight are still prone to type 2 diabetes, but also why some people are more susceptible to it than others.
It could be that a certain kind of fat is what makes people prone to type 2 diabetes, regardless of their weight.
Ceramides triggered insulin resistance, diabetes in mice
Senior author Scott Summers, Ph.D., chairman of the University of Utah Department of Nutrition and Integrative Physiology, believes it might be a toxic class of fat metabolites called ceramides that causes type 2 diabetes.
The new research from Summer and team shows that a buildup of ceramides prevents the fat tissue from working normally in mice.
When we overeat, some of the excess fat gets either stored or burned for energy. But for some people, excess fat just turns into ceramides.
"Ceramides impact the way the body handles nutrients. They impair the way the body responds to insulin, and also how it burns calories."
Scott Summers, Ph.D.
When too many ceramides accumulate in the fat tissue, the body reaches a "tipping point," as Summers puts it. Fat tissue stops working properly, and fat overspills into the blood vessels, heart, or goes on to damage the peripheral tissues.
Ceramides have previously been linked to diabetes by at least three different mechanisms: they cause the death of pancreatic beta cells, they increase insulin resistance, and they reduce insulin gene expression.
The new study further emphasizes the role of ceramides in creating insulin resistance.
Adding extra ceramides to fat cells in mice made them insulin-resistant and unable to burn calories. Conversely, mice that had fewer ceramides did not develop any insulin resistance.
Mice with excessive ceramides were also more likely to develop diabetes and fatty liver disease.
The results of the study were published in the latest issue of Cell Metabolism.
Implications for further research
This study suggests that some people are predisposed to turning excess fat into ceramides instead of calories.
"[The research] suggests some skinny people will get diabetes or fatty liver disease if something such as genetics triggers ceramide accumulation," said lead author Bhagirath Chaurasia, assistant professor at the University of Utah.
Summers points out that some Asian countries have a higher diabetes rate than the U.S., even though the obesity rate is relatively low.
Diabetes has already been linked to certain races/ethnicities, with African-Americans, Hispanics, Native Americans, some Asians, and Native Hawaiians or other Pacific Islanders being at a particularly high risk for type 2 diabetes, according to the CDC.
"Some people are just not made to deal with dietary fat," says Summers. "It's not just how much you eat, because some people can eat a lot and they just store all the fat effectively and remain healthy."
As a consequence, the scientists are now looking at genetic mutations that might make people predisposed to accumulating ceramides.
According to the researchers, ceramide levels predict the existence of diabetes in humans better than obesity. Patients in Singapore who received gastric bypass surgery, although all obese, had different levels of ceramides in their body. Those with lower levels did not have type 2 diabetes, whereas those diagnosed with the disease had higher levels of the toxic metabolites.
Summers is currently working to develop drugs that might inhibit ceramide synthesis.
"By blocking ceramide production, we might be able to prevent the development of type 2 diabetes or other metabolic conditions, at least in some people," adds Chaurasia.