Childhood Metabolic Markers of Adult Morbidity in Blacks

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.