Study links large waistline to increased risk of heart problems and type 2 diabetes

Researchers at Eastern Virginia Medical School’s Strelitz Diabetes Center and the school’s department of physiological sciences have published research showing a strong link between a large waistline and increased risk of Type 2 diabetes and cardiovascular disease.

The research focuses on fat in the midsection in patients undergoing weight-loss surgery.  The scientists reported on early findings in an abstract presented at the American Diabetes Association meeting in June. With the study now complete, the final results have been published in the journal of Biomedical and Biophysical Research Communications.

The study is being conducted in conjunction with Stephen G. Wohlgemuth, MD, medical director of bariatric surgery at Sentara Norfolk General Hospital’s Metabolic & Weight Loss Surgery Center and an assistant professor of clinical surgery at EVMS.

Based on samples of fat and blood from weight-loss surgery patients participating in the study, the researchers determined that protein-based enzymes called 12-lypoxygenase and 15-lypoxygenase are much more common or “active” in visceral fat — the  deep fat in the belly region surrounding the organs — compared to fat just under the skin’s surface, like cellulite.  

“We know that people with large amounts of visceral fat are more likely to have metabolic syndrome — high blood pressure, high cholesterol and insulin resistance — relative to people with primarily subcutaneous fat,” says Dr. Wohlgemuth. “People with large amounts of visceral fat generally have large bellies whereas individuals with larger amounts of subcutaneous fat typically have a bigger bottom and thighs,” he explains.

“Beta cells create the insulin which allows our bodies to convert the glucose in food into energy,” explains Jerry Nadler, MD, director of the EVMS Strelitz Diabetes Center and one of the study’s authors. “It is generally understood that the beta cell death that occurs in diabetes is caused by inflammation. What we’ve now determined is that the inflammation is triggered by these lipoxygenase enzymes.”

In fact, Anca Dobrian, PhD, assistant professor of physiological sciences and lead author of the study says 15-lipoxygenase was only found in the visceral fat. “Activation of this inflammatory enzyme in belly fat specifically has important implications for future treatment of obesity-related health problems,” she says.

Dr. Nadler believes that the presence of these lipoxygenase genes and proteins may explain why visceral fat is linked to Type 2 diabetes and cardiovascular disease.

“We found lipoxygenase in both the blood vessels and immune cells of visceral fat,” says Dr. Dobrian. “We determined that different forms of the lipoxygenase enzymes are preferentially expressed in vascular cells and we are now trying to understand the role of the enzyme as a possible link between vascular and fat inflammation. Dr. Dobrian and the research team anticipate that these studies will translate well into treatments for patients with diabetes and cardiovascular disease.

"It is very exciting that our team has identified damaging forms of lipoxygenases in only the visceral fat of these obese patients," Dr. Nadler says. "This indicates the potential to develop new medications to target particular forms of lipoxygenases and reduce inflammation in the fat to help prevent the diabetes and heart-related complications of obesity."

Ultimately, these findings could lead to a better understanding of the link between large waistlines and major diseases afflicting the U.S. population. These results may also allow scientists to develop new drugs to target the particular lipoxygenase pathway as a means to treat diabetes and cardiovascular complications.

These findings come at a critical time, too.  According to a new analysis by UnitedHealth Group’s Center for Health Reform and Modernization, more than 50 percent of Americans could have diabetes or pre-diabetes by 2020 at a cost of $3.35 trillion over the next decade if current trends continue.

About EVMS:

EVMS was founded by the community in 1973 to improve health through teaching, discovering and caring. The collaborative culture at EVMS draws like-minded students and faculty from all over the country, encourages a multidisciplinary approach to healthcare and emphasizes translational research. In just 36 years, the school has grown from 24 students to an economic footprint exceeding $700 million annually in the region of southeastern Virginia known as Hampton Roads. Learn more at www.evms.edu.