Blacks are at increased risk for obesity, type 2 diabetes mellitus and cardiovascular disease. A common pathogenetic link among these entities is insulin resistance/hyperinsulinemia.

The specific aims of this project are: 1) to compare skeletal muscle lipid content (SMLC) in black vs white children by computed tomography (CT) scan of the mid-thigh, and assess the relationship to in vivo insulin sensitivity; 2) to test the hypothesis that free fatty acid (FFA) - induced insulin resistance is associated with larger increases in intramyocellular lipid (IMCL) in black vs white adolescents; 3) to examine if β-cell insulin secretion in prepubertal black children is more sensitive to the stimulatory effect of FFA than in whites; and 4) to test if the β-cell in black obese adolescents is more susceptible to the lipotoxic effect of FFA compared with whites. The methods to be used are: the well- established CT method as well as Magnetic Resonance Spectroscopy (1H-MRS) to assess SMLC and IMCL; intralipid infusion to elevate circulating FFA levels; the hyperinsulinemic-euglycemic clamp with stable isotopes and indirect calorimetry to measure insulin sensitivity and substrate turnover; the hyperglycemic clamp to assess insulin secretion; DEXA and whole body MRI for body composition assessments.

Inclusion Criteria:

Protocols 1 & 4:

• Age 11-17 years
• Male or Female
• Healthy
• Obese, BMI ≥ 95 percentile
• Pubertal/Tanner Stage II-V
• African American or White American, based on self identity with no admixture for 3 generations

Protocol 2:

• Age 11-17 years
• Male or Female
• Healthy
• Normal Weight, BMI 10- 95 percentile
• Pubertal/Tanner Stage II-V
• African American or White American, based on self-identity with no admixture for 3 generations

Protocol 3:

• Age 8-12 years
• Male or Female
• Healthy
• Normal Weight, BMI 10-95 percentile
• Prepubertal/Tanner Stage I
• African American or White American, based on self-identity with no admixture for 3 generations

Exclusion Criteria:

• Medications which interfere with metabolism
• Hemocue < 12 gm/dl in pubertal subjects and <11gm/dl in prepubertal subjects
• Positive serum pregnancy test
• Recent significant weight change or dieting
• Presence of disease (i.e.diabetes, hypothyroidism, genetic dyslipidemia, etc)

Healthy black and white volunteers who are 8 to 17 years of age