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National Study Focuses on Families of People with Diabetes and Obesity

A new national research project headquartered at Wake Forest University School of Medicine will study three generations of family members to determine how many of the precursors to adult onset (Type 2) diabetes and obesity are inherited.

The study will begin with patients currently participating in the national Insulin Resistance Atherosclerosis Study (IRAS) and extend to their families.

Lynne E. Wagenknecht, Dr. P.H., the project director, said, "The project will determine to what extent insulin resistance and obesity are inherited and which gene or genes are responsible for them."

She said insulin resistance is a condition that leads the body to produce excess insulin, cholesterol and body fat and appears to be a risk factor for heart disease.

"The study design best suited to answer this question is a family study, where a large number of family members - brothers, sisters, their parents, and their children - are recruited," said Wagenknecht, associate professor of public health sciences (epidemiology) at Wake Forest.

As in IRAS, the national coordinating center for the IRAS Family Study will be at Wake Forest, and the clinics will be in San Antonio, Tex., San Luis, Colo., and Los Angeles, Calif. The IRAS study involved 1,600 men and women between 40 and 69.

Donald W. Bowden, Ph.D., professor of biochemistry and internal medicine (endocrinology/metabolism) at Wake Forest, will direct the study''s genetics laboratory.

The total cost of the study, paid for by the National Institutes of Health, will be about $10.4 million. Grants to Wake Forest total $4.1 million.

Wagenknecht said 160 IRAS participants will be selected, each with families of 9-13 members. But because of the greater risk of diabetes for Hispanics and African-Americans, two- thirds of the families to be recruited will be Hispanics and one-third African-Americans.

She said the average participant in IRAS was now in his or her 60s, which would put their parents in their 80s and their children in their 30s or 40s. The study also will analyze brothers and sisters of IRAS participants.

Insulin sensitivity will be measured by a glucose tolerance test to determine the ability of the participant''s body to use glucose, the key sugar produced in the process of digesting carbohydrates.

The obesity analysis will be by direct measurement - CT scans that can determine the amount of abdominal fat and quantify excess abdominal fat. Excess fat around the middle is considered a much greater heart disease risk than the same amount of fat distributed elsewhere in the body.

"DNA will be collected from blood samples to do analysis of specific genes known to be associated with heart disease and obesity," Bowden said. "We will also look for yet undiscovered genes associated with these disorders."

Bowden will coordinate the collection of the DNA samples from the three clinics and family members. The DNA samples then will be run through a genome screen by the Mammalian Genotyping Service in Marshfield, Wis., to find chromosomal regions for further study in Bowden''s laboratory.

The researchers have the expectation that a number of genes likely will be involved.

Wagenknecht emphasized that the study probably will not result in a precise gene or genes, but rather indicate on which areas of which chromosomes the potential genes might lie. "Finding the gene will take years and years of additional work."

Wagenknecht said she expected the study would be able to add new knowledge about the interaction between genes and environmental factors such as diet.

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