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Researchers have known for about 25 years that atherosclerosis or hardening of the arteries begins in childhood. But it has taken time to find markers for artery disease and to see if the markers important for problems in adults also are significant in children.

Now Dr. Steven Shea, the Hamilton Southworth Professor of Medicine at P&S and professor of epidemiology at the Mailman School of Public Health; Dr. Richard Deckelbaum, the Robert R. Williams Professor of Nutrition at P&S, and colleagues have published two new studies that characterize the relationships of atherosclerosis markers to obesity and physical fitness in children and young adults.

Both studies looked at C-reactive protein, a marker of systemic inflammation that is produced in the liver. High levels of C-reactive protein are a known predictor of heart disease, cardiovascular problems, and type 2 diabetes in adults.

The first study, published in the January issue of Obesity Research, looked at obesity, levels of fasting insulin and C-reactive protein in the blood. Obesity is associated with higher than normal levels of insulin and C-reactive protein in older children and adults but little is known about these associations in very young children.

Data came from 491 healthy, non-obese 2- to 3-year-old Hispanic children—255 boys and 236 girls—enrolled in a dietary study in New York City from 1992 to 1995. To calculate body fat, the researchers used two indices that rely on height and weight—body mass index (weight in kilograms divided by height in meters squared) and ponderal index (weight in kilograms divided by height in meters cubed). They also took four skinfold measurements at the shoulder blade, triceps, waist, and hip, which show the amount of fat in specific regions of the body. Waist and hip circumferences were noted and blood was drawn to measure C-reactive protein and fasting insulin and glucose levels. The children in the study weighed slightly more than the national average.

The researchers found that greater body mass index, even in very young children, is associated with higher fasting insulin levels and that fasting insulin is associated with C-reactive protein level.

The researchers saw no observable relation of fasting glucose level with the body fat measurements, indicating that glucose equilibirium was maintained despite higher fasting insulin levels among the children with above average weights. But the findings that the children with higher body mass index had higher fasting insulin levels indicate that insulin resistance, a potential warning sign for type 2 diabetes, begins much earlier in life than previously thought.

The second study is one of the first investigations of physical fitness and C-reactive protein level in older children and young adults. The study looked at 205 children and young adults—110 females and 95 males—who ranged in age from 6 to 24 years. They were participants in the Columbia University BioMarkers Study, a study of Hispanic and non-Hispanic caucasian children and their parents conducted from 1994 to 1998. As in the other study, the researchers measured height, weight, body mass index, skinfolds, waist and hip circumferences, and C-reactive protein level in blood samples. The presence of family history of early-onset heart disease also was noted. The children walked on a treadmill to assess their physical fitness.

The researchers found that the more physically fit children are, the lower their levels of C-reactive protein and vice versa. They saw the relationship even after adjusting for age, gender, ethnicity, family history of heart disease, and measures of obesity. The findings, which appeared in the February issue of Pediatrics, are consistent with other research in adults and children that link lack of physical fitness to established cardiovascular disease risk factors, including high cholesterol, blood pressure, and obesity.

"Our research shows that children—even very young children—need to have a healthy lifestyle to prevent obesity and maintain a good level of physical fitness," Dr. Deckelbaum says. "Otherwise they could be starting early on a path to heart disease."

Drs. Shea and Deckelbaum are continuing to examine blood samples from some of the children in the biomarkers study to look at additional markers and genes that appear to be important in obesity in kids and their families.

"We are looking at gene polymorphisms associated with obesity and insulin irregularities," Dr. Deckelbaum says. "Ultimately we'd like to come up with a genetic risk profile to find out whether some families are more predisposed than others."

The studies were supported by grants from the National Institutes of Health.


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