Unhooking the Obesity-Diabetes Connection

27 july 2009-- Scientists may be closer to solving a medical mystery with huge implications for personal and public health: Why obese people are prone to developing type 2 diabetes.

A series of studies appearing online July 26 in Nature Medicine suggest that inflammation within the fat tissues of heavy individuals could trigger the blood sugar disease.

What's more, each of the four completely independent studies, from two continents and three countries, showed that interfering with these immune-cell processes actually reversed diabetes in mice.

The long-term implications of the findings are enticing: perhaps one day a cure for type 2 diabetes, a condition that now plagues more than 23 million people in the United States alone.

"This group of papers suggests that cellular immunity may regulate inflammation in fat," said Dr. Vivian Fonseca, professor of medicine at Texas A&M Health Science Center College of Medicine and director of the Diabetes Institute at Scott & White. "The authors do suggest that if you change the inflammatory response by changing the way the body cells respond to a trigger for inflammation, you might be able to get at the real heart of diabetes and that suggests you could cure it."

But Fonseca warned, all these studies were conducted in mice and have yet to be proven in humans

In type 2 diabetes, the body often becomes resistant to insulin and doesn't use it effectively. In the last decade or so, researchers have presented evidence that suppressing inflammation in animals could improve insulin resistance and other processes involved with diabetes. Inflammation is now widely believed to be involved in many metabolic diseases afflicting obese individuals. Inflammation in fat tissue, in particular, seems to be a culprit, by changing fat tissue function, thereby contributing to insulin resistance.

But the exact mechanisms of the phenomenon have been unclear.

Three papers, one from Japan, one from Canada and one from the United States, showed that immune system cells known as T cells were deficient in obese mice, pushing the immune system to somehow initiate insulin resistance.

Restoring T cells to more normal levels actually reversed weight gain and improved insulin resistance, even when the mice continued on a high-fat diet.

The fourth study looked at another class of immune cells called mast cells, which are more commonly linked to allergies.

An over-abundance of mast cells contributed to obesity and diabetes in mice, but when mast cells were removed from the system the problem was corrected, explained study senior author Guo-Ping Shi, a biochemist with Brigham and Women's Hospital in Boston.

"We gave mice a high-fat diet for three months and they developed obesity and diabetes," he said. But mice that had been stripped of mast cells did not. "These mice are protected from the disease if they are without these cells," Shi said.

Shi's team also gave wild-type ("normal") mice allergy medicines, which work to "stabilize" mast cells. This also led to improvements in the mice.

"We can use the drugs to manipulate cell activity or prevent disease in this case," Shi said.

Shi said he has signed a contract with a local company to develop a version of the drugs to combat diabetes in humans.

More information

There's more on type 2 diabetes at the American Diabetes Association.