Childhood Metabolic Markers of Adult Morbidity in Blacks

Study Overview
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Brief Summary
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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.

Official Title
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Childhood Metabolic Markers of Adult Morbidity in Blacks

Conditions
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Healthy, Normal Weight, Overweight

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Protocol 1<br>Healthy, overweight 11 to 17 year old black and white adolescents | |
| Protocol 2<br>Healthy, normal-weight 11 to 17 year old black and white adolescents | |
| Protocol 3<br>Healthy, normal-weight 8 to 12 year old black and white adolescents | |
| Protocol 4<br>Healthy, overweight 11 to 17 year old black and white adolescents | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle lipid content, insulin sensitivity and insulin secretion |  | Assessments at 2 timepoints occur within a 2 to 3 week period |