Type 2 diabetes is widely recognized as an emerging public health crisis, and a biomedical research team including Wang believes that systems-identification and analysis often used in engineering might provide part of the solution.
Yue (Joseph) Wang demonstrates the protein array analyzer in the Center for Genetic Medicine at Children’s National Medical Center.
Type 2 diabetes is a disease in which a person’s cells lose their ability to use the body’s insulin (a hormone produced in the pancreas) to convert glucose (a sugar molecule) to energy. Patients with diabetes have increased risks of heart attack, stroke, and depression as well as blindness and kidney damage.
Epidemic in USA
Formerly called adult-onset diabetes, Type 2 diabetes develops mostly in people over age 50. Recently, however, it is increasingly diagnosed in younger people, including children. The number of cases is rising worldwide and the disease is considered epidemic in the United States. The U.S. Center for Disease Control reported last fall that babies born in 2000 will have a 33 to 50 percent chance of developing the disease with an accompanying 11- to 18-year reduced life expectancy. Males have a 1 in 3 chance of developing diabetes; females a 2 in 5 chance; and Hispanic females a 1 in 2 chance.
Genetic and Controllable Factors
Although diabetes has a genetic component, many controllable factors are involved in the disease, particularly excess weight and lack of exercise. The key to the disease is considered to be insulin resistance, a phenomenon where the glucose needed for cell energy cannot penetrate the cell wall. “Cells use insulin to help the sugar penetrate the membrane,” Wang explained. “Insulin resistance is not well understood, but the cells apparently ‘forget’ how to utilize it,” he said.
Insulin resistance is most noted in muscle cells, he said. “People who exercise have a much lower chance of developing diabetes. Even patients who are already diagnosed with Type 2 diabetes can reduce their insulin resistance with as little as 20 minutes of exercise each day.”
He explained a commonly accepted theory behind insulin resistance describing that what are called ‘satellite’ cells in the muscles are responsible for generating new muscle cells. “These satellite cells never develop insulin resistance and can produce cells fully capable of utilizing insulin. However, if people are not exercising, they are not generating new muscle cells and, in Type 2 diabetes, their existing cells lose the memory of how to use insulin.”
Two of the major hurdles in understanding Type 2 diabetes are the lack of quantitative bio-markers that permit the design and testing of interventions and the high degree of multidimensionality of the problem, Wang said.
He is a member of several cancer research teams that are working on biomarker identification and systems analysis. “We realized our work on cancer can help in the fight against diabetes and we are developing projects to apply our tools and experience to the problem,” he said.
One project under development involves a large-scale exercise intervention involving a group considered pre-diabetic and a group already diagnosed with the full-blown disease. The multidisciplinary project would collect data on blood tests, psychological assessment, food access, and genetic predisposition. Information at the molecular level would include whole-genome messenger RNA profiles of the muscle tissue and the response of the blood chemistry and muscle to different drugs.
The team hopes to develop a model of the interactions within the complex system of factors. “This is an incredibly complex system, and we hope eventually to be able to identify the right factors and how they interact within the body in developing Type 2 diabetes,” Wang said. “It is a difficult problem that will require experts from dozens of different disciplines.”
Wang’s team is working with the biologists and clinicians from Duke University Medical Center, Children’s National Medical Center, and Hartford Hospital.
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