INCLUSION CRITERIA:
Good general health. Individuals taking medications for obesity-related comorbid conditions will not be excluded.
Obesity: body mass index for age and triceps skinfold above the 95th percentile (determined by NHANES I age-, sex-, and race- specific data). All subjects will be required to be over 60 kg in body weight.
Evidence for a quantifiable obesity-related comorbidity. Examples include: systolic or diastolic hypertension (determined by age-specific charts); frank Type 2 diabetes, impaired glucose tolerance assessed by oral glucose tolerance testing; hyperinsulinemia (defined as a fasting insulin greater than 15 mIU/mL); significant hyperlipidemia (total cholesterol greater than 200 mg/dL, LDL cholesterol greater than 129 mg/dL or fasting triglycerides greater than 200 mg/dL); hepatic steatosis (SGPT or SGOT above normal range with negative hepatitis studies) or sleep apnea documented by a sleep study.
Age 12 to 17 years at the start of the study.
For girls with childbearing potential, a negative pregnancy test before taking and while taking study medication. Sexually active females must be using an effective form of birth control. These methods include total abstinence (no sex), oral contraceptives ("the pill"), an intrauterine device (IUD), levonogestrol implants (Norplant), or medroxyprogesterone acetate injections (Depo-provera shots). If one of these cannot be used, contraceptive foam with a condom is recommended.
Race of all four grandparents self-identified as either all Caucasian or all African American.
EXCLUSION CRITERIA:
Volunteers will be excluded (and referred to non-experimental treatment programs) for the following reasons:
Presence of renal, hepatic (other than obesity-related steatosis), gastrointestinal, most endocrinologic (e.g., Cushing syndrome), or pulmonary disorders (other than either asthma not requiring continuous medication or sleep apnea-related disorders);
Adolescent girls who are pregnant, who are currently nursing an infant, or who are having unprotected intercourse;
Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study;
Subjects who regularly use prescription medications unrelated to the complications of obesity. Oral contraceptive use will be permitted, provided the contraceptive has been used for at least two months before starting study medication. The use of over-the-counter and prescription medications will be reviewed on a case-by-case basis; depending on the medication, subjects who have continued to take prescription medication for at least 3 months prior to study entry may be eligible;
Recent use (within six months) of anorexiant medications for the purpose of weight reduction;
Inability to undergo MRI (e.g., volunteers with metal within their bodies including 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. that are contraindications).
For pilot study participants, hypersensitivity or allergy to methylene blue. Individuals with documented G6PD deficiency will be excluded.
INCLUSION CRITERIA: HEALTHY CONTROL CHILDREN AND ADOLESCENTS:
Volunteers will qualify for inclusion if they meet the following criteria:
1. Good general health.
2. Age 12-17 years at study entry.
3. Body mass index (BMI) for age above the 5th percentile and below 85th percentile, which is considered normal weight by CDC growth chart standards.
4. For females with childbearing potential, a negative pregnancy test at initial evaluation.
5. Race of all four grandparents self-identified as either all Caucasian or all African American.
EXCLUSION CRITERIA: HEALTHY CONTROL CHILDREN AND ADOLESCENTS:
Volunteers will be excluded for the following reasons:
1. Presence of past or present medical problems which would impair performance during the exercise tests;
2. Females who are pregnant, or who are currently nursing an infant;
3. Individuals who have, or whose parent or guardian has, current substance abuse or a psychiatric disorder or other condition that in the opinion of the investigators would impede competence or possibly hinder completion of the study;
4. Recent weight change of more than 3% of body weight in the past two months;
5. Recent use (within six months) of anorexiant medications for the purpose of weight reduction;
6. Physical impairments that would prevent completion of either the walk/run test or the cycle test.
Warren Grant Magnuson Clinical Center (CC)