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Genetic Defect May Cause Type 2 Diabetes

Study focuses on children of parents with the disease

THURSDAY, Feb. 12, 2004 (HealthDayNews) -- An inherited defect that causes an energy shortage in the powerhouses of the body's cells may be a major factor in development of type 2 diabetes in children of parents with the disease, new research suggests.

In a study published in the Feb. 12 issue of the New England Journal of Medicine, researchers say mitochondria -- the cells' energy centers -- don't appear to function properly in the children of parents with type 2 diabetes. That could lead to an accumulation of fat inside muscle cells and development of insulin resistance, a hallmark of type 2 diabetes, the researchers say.

Insulin, a hormone produced in the pancreas, promotes the transfer of glucose, or blood sugar, into cells for energy production and storage. Mitochondria within the cells convert glucose and fat into energy through oxidation.

The study compared insulin-resistant children of parents with type 2 diabetes with a control group with normal insulin sensitivity. The people in both groups, who averaged about 27 years old, were lean, and matched for age, weight, height and activity levels. None had diabetes.

Besides the dysfunctional energy centers in the cells, the insulin-resistant individuals had no other factors that would contribute to insulin resistance, says study author Dr. Gerald I. Shulman. He is an investigator at the Howard Hughes Medical Institute and a professor of internal medicine and cellular and molecular physiology at the Yale University School of Medicine.

The researchers looked at whether the muscle cells in the insulin-resistant offspring were getting increased amounts of fatty acids from the fat stored in fat cells, but found no difference between the two groups.

The researchers, however, did find the insulin-resistant children had a 30 percent reduction in mitochondrial function in their muscles, compared with the control group.

"What we hypothesize is that these insulin-resistant offspring inherit genes that result in a reduction in mitochondrial content," Shulman says. "This predisposes them to accumulate fat inside the muscle cells, resulting in insulin resistance, which in turn will lead them to develop diabetes later in life."

Shulman and his team are now trying to identify the genes responsible for the altered mitochondrial function. They're also studying whether the insulin resistance results from lower mitochondrial function, a lower number of the mitochondria in muscle cells, or both. The researchers are also looking into whether a reduction in mitochondrial function can be reversed by exercise.

Fat accumulation in muscles can result in insulin resistance, Shulman says. And earlier research by Shulman and his colleagues found elderly people also develop insulin resistance because of reduced mitochondrial function. But Shulman believes the changes in the elderly are part of the normal aging process.

The new study focused on 14 insulin-resistant people and a control group of 12. Researchers measured fat content inside the muscle cells and mitochondrial energy production.

The findings could form the basis for further research that might lead to medications to improve mitochondrial function. This, in turn, could be used in the treatment or perhaps even prevention of type 2 diabetes, Shulman says.

"In addition, these data will help us to find the genes responsible for type 2 diabetes," he says.

For now, exercise can increase mitochondria content as well as fat oxidation in muscle, and diet and exercise can play a key role in preventing type 2 diabetes, Shulman says.

Diabetes is a disease in which the body does not produce or properly use insulin, which converts sugar, starches and other food into energy. The cause of diabetes remains unknown, though both genetics and factors such as exercise and diet appear to play roles, the American Diabetes Association (ADA) says.

About 17 million Americans who are diagnosed with diabetes have type 2 diabetes, the ADA says. But some 5.2 million people who have diabetes don't know it. Complications of type 2 diabetes can include heart disease, blindness and nerve and kidney damage.

More information

For more on type 2 diabetes, visit the American Diabetes Association or the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCES: Gerald I. Shulman, M.D., investigator, Howard Hughes Medical Institute, Chevy Chase, Md., and professor, internal medicine and cellular and molecular physiology, Yale University School of Medicine, New Haven, Conn.; Feb. 12, 2004, New England Journal of Medicine
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