Metabolic Differences of Overweight Children and Children of Overweight Parents

African Americans have a greater prevalence than Caucasian Americans of hypertension,
non-insulin-dependent diabetes mellitus, and cardiovascular disease. These conditions lead to
substantial excess morbidity and mortality and are associated with and exacerbated by
obesity, the prevalence of which is strikingly elevated in African American women. It is
unknown if this increased prevalence of comorbid conditions is solely related to the greater
prevalence of severe obesity among African American women, or due to differences in insulin
sensitivity, glucose disposal, body composition, or fat cell metabolism. Through this
project, we have verified that many of the physiological differences observed between African
American and Caucasian adults are already present in obese children and in children at high
risk for developing obesity. However, the roles that differences in energy expenditure,
glucose metabolism, body composition, and other factors play in determining which children
develop obesity and its comorbid conditions in adulthood remain unclear. In this study, we
compare body composition, total and resting energy expenditure, and glucose disposal of obese
African American and Caucasian children and of non-obese children of obese African American
and Caucasian parents, to characterize the timing and nature of factors that may contribute
to the prevalence of obesity and its complications. We also relate serum levels of the
body-fat related circulating factors such as leptin, to these measures, and obtain samples
for genomic DNA isolation from participants and their parents to characterize the roles of
genes felt important for the development of obesity. We will follow these children for 15
years, studying them intensively at 5 year intervals until adulthood.

- INCLUSION CRITERIA:

Volunteers will qualify for inclusion under this protocol if they meet the following
criteria:

1. Good general health. Individuals with renal, hepatic, most endocrinologic (e.g.
hypothyroidism, or Cushing syndrome), or pulmonary disorders (other than mild asthma
not requiring chronic medication) will be excluded.

2. For obese subjects, body mass index for age above the 85th percentile (determined by
NHANES I age-, sex-, and race-special data). For normal weight subjects of obese
parents, body mass index (determined by NHANES I age-, sex-, and race- specific data)
between the 5th and 85th percentile and both parents' current body mass index above 25
kg/m(2), or a history of a body mass index above 25 kg/m(2).

3. No significant psychiatric illness.

4. At initial visit, Tanner I (prepubertal) or Tanner II (early pubertal) pubic hair and
breast stage of development for girls, and Tanner I or Tanner II pubic hair and testes
size (6ml) for boys.

5. Subjects must be able to undergo MRI. Volunteers with metal in their bodies that are
contraindications for MRI will be excluded. These include cardiac pacemakers, neural
pacemakers, aneurysmal clips, shrapnel, ocular foreign bodies, cochlear implants,
non-detachable electronic or electromechanical devices (such as infusion pumps, nerve
stimulators, bone growth stimulators, etc.).

6. Age 6 to12 years at the start of the study.

7. For girls who have been followed to an age when they are menstruating (or are of an
age when pregnancy is a possibility), a negative pregnancy test.

8. Race of all 4 grandparents self-identified either as all Caucasian or all African
American.