It's no secret there is a diabetes epidemic in this nation. The prevalence rate for type 2 diabetes has increased right along with the girth of the population.

 

Published data from the Centers for Disease Control and Prevention for 2007 (the last year available) states an estimated 23.6 million people in America have diagnosed or undiagnosed diabetes. Even more alarming, based on the percentage of Americans with impaired fasting glucose, it is estimated that an additional 57 million Americans age 20 and older have prediabetes … slightly more than one-quarter of the adult population.

 

Age is certainly a factor — in 2007, the percentage of people with diagnosed or undiagnosed diabetes jumped from 10.7 percent of the population age 20 and over to 23.1 percent of the population age 60 or older — but weight is an even bigger issue.

 

For type 2 diabetes, which accounts for 90-95 percent of all diagnosed cases of diabetes in adults, obesity and overweight are key risk factors. The good news is the Diabetes Prevention Program showed moderate lifestyle interventions to lower weight and increase physical activity had big pay-offs in terms of reducing the likelihood of prediabetic participants progressing to type 2 diabetes. These modest behavioral changes actually reduced the incidence rate 58 percent during a three-year period. For participants 60 or older, the reduction in the development of the disease was even greater at 71 percent.

 

Unfortunately, physicians are all too aware of the high percentage of patients with good intentions who fail to make sustained behavioral modifications. Enter Roger D. Cone, PhD, professor and chair of Molecular Physiology and Biophysics at Vanderbilt University Medical Center. "I work on how the brain regulates body weight," said the researcher who recently received the 2009 Donald F. Steiner Award for Outstanding Achievement in Diabetes Research. "My group discovered one of the first genes demonstrated to cause obesity in humans."

 

He continued, "The relationship with diabetes is that obesity is responsible for a very large percentage of type 2 diabetes … maybe as much as 80 percent."

 

Cone, who moved to Nashville 15 months ago from his previous position at the Center for the Study of Weight Regulation at Oregon Health and Science University, was recruited to launch the Vanderbilt Institute for Obesity and Metabolism. The goal, he added, is to "provide resources and cause synergy among investigators studying obesity and other metabolic disorders and co-morbid conditions such as diabetes."

 

Cone and his colleagues identified the critical role the melanocortin system, which is a key neural circuit that senses and responds to fat reserves, plays in the adipostat — a collective group of specialized brain cells present in humans and other mammals that regulates body weight, much like a programmable thermostat regulates a home's temperature. The central melanocortin system, which is leptin-responsive, is accountable for keeping energy stores relatively constant.

 

"It turns out that energy is maintained homeostatically, much like blood glucose or blood sodium," Cone explained. "Leptin acts on the circuits in the brain. When leptin goes down, the body thinks it's in starvation mode. The brain decreases the rate at which you use energy and increases the hunger drive to try to regulate energy back to previous levels."

 

Mutations in the melanocortin 4 (MC4) receptor at the heart of the adipostat are thought to be a major cause of the most severe forms of obesity.

 

Unfortunately, Cone continued, there currently isn't a way to break the cycle when the melanocortin system goes into false starvation mode. The only option right now is through bariatric surgery, and even that drastic measure has the potential to be sidestepped if a patient is determined to do so. "There is no pharmaceutical solution. There is no magic diet," he stated.

 

Cone added the efficiency of the adipostat is a key reason why it's so hard for people to effectively lose weight and keep it off. The "memory" of the previous weight makes the melanocortin system burn more efficiently and work to get the body back to the old weight.

 

"That said," he continued, "my group and others are trying to understand the adipostat in more detail. Vanderbilt has a fantastic drug discovery program. We are already looking for drugs that act on the MC4 receptor. If we could find a way of resetting the receptor, we possibly could turn around severe obesity … and moderate obesity."

 

While a "magic pill" may someday exist to reprogram the body's adipostat, Cone stressed there is a lot of evidence that exists right now showing good nutrition and fitness make a huge difference.

 

"The Diabetes Prevention Program demonstrated that with marginal weight loss, the incidence of diabetes could be significantly reduced," Cone said, adding that it only takes a little cutting back and an increase in moderate activity like walking to see improvements in glucose production and efficiency.