Healthy, Normal Weight, Overweight
Conditions
Brief summary
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.
Interventions
None listed
Sponsors
Study design
Eligibility
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Skeletal muscle lipid content, insulin sensitivity and insulin secretion | Assessments at 2 timepoints occur within a 2 to 3 week period |
Countries
United States