Link between obesity and diabetes found

Researchers have now identified a critical link between obesity and diabetes.

It's by now well established that obesity is a major risk factor for diabetes. But what exactly is it about extra body fat that leads to insulin resistance and blood glucose elevation, the hallmarks of diabetes?

Over the past several years, Beth Israel Deaconess Medical Center (BIDMC) endocrinologist Barbara Kahn, MD, has developed a large body of research suggesting that a molecule called retinol binding protein 4 (RBP4) plays a key role in the process.

Kahn's lab was the first to show that elevated levels of RBP4 - previously known only for its role as a transport protein for Vitamin A - led to the development of insulin resistance in animal models.

Additional work revealed parallel results in human blood samples: obese, insulin-resistant individuals had high RBP4 levels and lean, insulin-sensitive people had low RBP4 levels. Furthermore, people with genetic changes in RBP4 that resulted in high blood levels of the protein had an elevated risk of developing diabetes.

Now, Kahn and her colleagues explain the mechanism by which RBP4 contributes to increased risk of diabetes.

In a new study, the investigators describe how the protein sets in motion a complex interplay between two branches of the body's immune system, leading to chronic fat tissue inflammation and, ultimately, insulin resistance.

"Although the inflammatory response is a key part of our immune system and an important means of protection and tissue repair in response to infection or injury, under certain conditions of metabolic dysfunction, this response is activated even in the absence of foreign pathogens," Kahn, Vice Chair of the Department of Medicine at BIDMC and George Richards Minot Professor of Medicine at Harvard Medical School, said.

"It seems that in the case of obesity, RBP4 is acting like a foreign pathogen and provoking the immune system," she said.

As a result, she explains, the immune cells in fat tissue become activated and produce inflammatory signals that the body usually reserves to repair tissue that is damaged or infected.

This chronic inflammation then creates an environment that leads to insulin resistance, a state in which the body is unable to properly respond to insulin, the hormone that transports sugar from the blood into cells to be used for energy production and fuel storage.

The study is published online in the journal Cell Metabolism.