OBJECTIVE: To determine associations between directly measured insulin sensitivity (SI) and oral glucose tolerance test (OGTT)-derived plasma insulin values, or calculated SI indices, in overweight peripubertal Latino children at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty overweight Latino children with a family history of type 2 diabetes, aged 8-13 years, Tanner stages 1-2, underwent an OGTT. Fasting and 2-h plasma insulin values and OGTT-derived SI indices were compared with SI derived from a frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis, before and after adjustment for total body fat and lean tissue mass, or BMI. RESULTS: FSIGTT-derived SI for all subjects was 1.62 +/- 0.78 x 10(-4) min (-1) x (microU/ml), with no sex differences. SI correlated (all P values < 0.001) with fasting (r = -0.57) and 2-h (r = -0.58) plasma insulin and all SI indices (r = -0.57 to 0.67). After adjusting for total body fat and lean tissue mass, or BMI, the associations between SI and either fasting insulin or fasting SI indices were no longer significant. However, the 2-h insulin and post-glucose challenge SI indices maintained significant independent associations with SI, even after adjustment for body composition. CONCLUSIONS: In overweight, peripubertal Latino children at risk for type 2 diabetes, the 2-h plasma insulin value and postchallenge SI indices are better independent correlates of SI than fasting values, after accounting for body composition. The 2-h insulin may therefore be superior to fasting insulin as a single blood sample value for clinical or epidemiological estimates of SI, especially when combined with assessment of body composition.