In The Genes: Extra Belly Fat, Insulin Resistance Linked

February 24, 1999

About one-third of Americans carry enough extra weight to threaten their health. Yet some people who choose healthy lifestyles still seem to struggle to keep the pounds off. And those with apple-shaped profiles are considered at special risk.

For example, extra fat around the waist is estimated to increase a person's risk of diabetes and heart disease.

In the case of diabetes and weight gain, a recent study by researchers at Washington University School of Medicine in St. Louis suggests that some people may have the genetic cards stacked against them. Investigators from the Division of Biostatistics evaluated data from 512 sedentary family members. They found that people who have genes making them prone to accumulate a certain type of belly fat also are prone to develop resistance to the hormone insulin, which sets the stage for type II diabetes.

"We tried to find out if there's a common genetic factor that is shared among people who have a greater fat distribution at the abdomen and also have insulin resistance, and this appears to be the case," says Yuling Hong, M.D., Ph.D., assistant professor of biostatistics. Hong is lead author of a paper on the results in a recent issue of the Journal of Clinical Endocrinology and Metabolism.

What's inside the apple matters
Why focus on one form of abdominal fat? All owners of an apple-shaped profile aren't alike, it appears. Layers of fat that cushion the viscera, or internal organs, in the abdomen may be more detrimental to health than outer layers of belly fat.

"There is good evidence that this deeper, visceral fat is associated more with diabetes," says Dabeeru C. Rao, Ph.D., director of the Division of Biostatistics, professor of biostatistics and principal investigator for the study.

The researchers explored the link between diabetes and the thickness of this inner fat layer in Caucasian families who already were participating in a larger genetics study. As part of the Heritage Family Study, four field centers evaluated the volunteers: the University of Indiana, Texas A&M University, the University of Minnesota and Laval University in Quebec, Canada. The Heritage Family Study is funded by the National Heart, Lung, and Blood Institute.

For the smaller diabetes study, at least three children and both parents from each of the 98 families were evaluated. Scientists at the four field centers measured their abdominal visceral fat using computed tomography, an X-ray imaging technique that distinguishes between the two types of belly fat. They determined insulin resistance by measuring the fasting blood level of the hormone. Then Hong and his colleagues created family trees to determine which family members shared the two traits being evaluated and how closely they shared the traits.

A gene that plays a role in a disease will pass from the parent with the gene to some of the couple's children. By evaluating how often parents and children share a trait such as insulin resistance, researchers estimate the likelihood that genes underlie the trait.

The pattern of insulin resistance in the families suggested that 21 percent of the factors determining the likelihood of developing diabetes are inherited. And 40 percent of the likelihood for developing abdominal visceral fat appeared to result from genes. These findings agree with previous studies.

But what about susceptibility to abdominal fat and diabetes? To determine this likelihood, the investigators looked at how often a parent with insulin resistance had a child with extra belly fat and vice versa. If the same genetic factors favor two traits, one trait should appear more often than by chance in children of a parent bearing the other. In the study, 6 percent of the genetic factors associated with insulin resistance also influenced the accumulation of abdominal visceral fat.

This means that about one-third of the genetic factors that predispose people to insulin resistance also make them prone to accumulate the inner layer of belly fat.

The findings also are likely to apply to people of normal weight, Hong said, although the genes involved have yet to be identified. For now, the researchers hope the results will lead others to use direct measurements of abdominal visceral fat in future studies. The study also suggests that people who are overweight should periodically be checked for diabetes.

What's next?
As part of the Heritage Family Study, colleagues of the Washington University researchers have begun hunting for the disease-related genes in the 98 families. They are using genetic tags that help indicate the position of disease-related genes along the length of human chromosomes the way street names help locate someone's house.

Once genes linked to the traits are identified, tests could be developed to indicate a person's risk for becoming diabetic and gaining abdominal fat. Designing such tests would be easiest if a few -- or even one -- genes were responsible for the link.

Finding disease-related genes also may help clarify whether genes underlie the appearance of four traits in some families. High blood pressure, obesity, insulin resistance and high levels of fats in the blood called triglycerides all occur in some families, a condition that has been labeled syndrome x or metabolic syndrome. Insulin resistance and obesity are considered cornerstones of the syndrome.

The researchers note that people shouldn't ignore the important influence of diet and exercise on health, however. Non-genetic factors appear to account for more than 50 percent of the likelihood of developing insulin resistance or abdominal visceral fat, for example. In the diabetes study, the influence of lifestyle was factored in by evaluating families whose parents had lived together an average of 20 years and had older children.
Note: For more information, refer to Hong, Y. et. al. "Familial Clustering of Insulin and Abdominal Visceral Fat: The HERITAGE Family Study," Journal of Clinical Endocrinology and Metabolism, Vol. 83 (12): 4239-4245, December 1998.

Washington University in St. Louis

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