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OBJECTIVE - African American youth have lower insulin sensitivity than their Caucasian peers, but the metabolic pathways responsible for this difference remain unknown. Free fatty acids (FFAs) are associated with insulin resistance through the Randle cycle. The present investigation determined whether elevating FFA is more deleterious to insulin sensitivity in African American than in Caucasian adolescents.
RESEARCH DESIGN AND METHODS - Insulin sensitivity (3-h hyperinsulinemic-euglycemic clamp) was evaluated in 22 African American and 21 Caucasian adolescents on two occasions: 1) infusion of normal saline and 2) infusion of 20% intralipid.
RESULTS - During intralipid infusion, fasting insulin and C-peptide concentrations increased while fasting glucose and basal glucose turnover did not change in either group. Insulin sensitivity decreased similarly in African American (normal saline 7.65 ± 0.61 vs. intralipid 5.15 ± 0.52 µmol * kg^sup -1^ * min^sup -1^ per pmol/l) and Caucasian subjects (normal saline 8.97 ± 0.85 vs. intralipid 5.96 ± 0.56 µmol * kg^sup -1^ * min^sup -1^ per pmol/l) (P < 0.001).
CONCLUSIONS - African American and Caucasian adolescents respond to FFA elevation similarly through increased fasting insulin secretion to maintain fasting glucose homeostasis and reduced peripheral glucose uptake and insulin resistance. Thus, African American adolescents are not more susceptible to FFA-induced insulin resistance than Caucasian youth.
Diabetes Care 32:355-360, 2009
Free fatty acids (FFAs) are implicated in insulin resistance development through the Rändle cycle (1,2). In adults, elevating plasma FFA by infusing lipid emulsion inhibits glucose disposal and oxidation in normal-weight, obese, and type 2 diabetic patients (3-5). The only pediatric study was performed in Caucasian children and demonstrated that Intralipid infusion decreased insulin sensitivity in pubertal adolescents, with no such effect in prepubertal children (6). Such data support that pubertal insulin resistance is driven by the Rändle cycle/ substrate competition (7,8).
Insulin sensitivity is lower in African American children than in their Caucasian peers (9,10), but the metabolic pathways responsible for this contrast remain unknown. Lower insulin sensitivity correlates inversely with an increased fat-tocarbohydrate ratio in the diet of African American children (10,11). Thus, FFAs may be detrimental to insulin sensitivity in African American children. If racerelated differences in the susceptibility to FFA-induced insulin resistance exist, then this is of increased importance during puberty when increased FFAs decrease glucose...