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Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children, such as type 2 diabetes. Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults. However, very little is known regarding the effects of exercise on insulin resistance in youth. Therefore, we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes.Twenty-two overweight Latino adolescent males were randomly assigned to either a twice-per-week resistance training group (RT = 11) or a nonexercising control group (C = 11) for 16 wk. Strength was assessed by one-repetition maximum, body composition was quantified by dual-energy x-ray absorptiometry, and insulin sensitivity was determined by the frequently sampled intravenous glucose tolerance test with minimal modeling.Significant increases in upper- and lower-body strength were observed in the RT compared with the C group. The RT group significantly increased insulin sensitivity compared with the C group (P < 0.05), and this increase remained significant after adjustment for changes in total fat mass and total lean tissue mass (P < 0.05). Compared with baseline values, insulin sensitivity increased 45.1 ± 7.3% in the RT group versus −0.9 ± 12.9% in controls (P < 0.01).A twice-per-week 16-wk resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition.