IMPORTANCE: Latino youths are disproportionately impacted by prediabetes and type 2 diabetes (T2D). Lifestyle intervention is the first-line approach for preventing or delaying T2D among adults with prediabetes. OBJECTIVE: To assess the efficacy of a diabetes prevention program among Latino youths aged 12 to 16 years with prediabetes. DESIGN, SETTING, AND PARTICIPANTS: This 2-group parallel randomized clinical trial with 2:1 randomization assessed a lifestyle intervention against usual care among Latino youths with prediabetes and obesity with 6- and 12-month follow-up. The study was conducted at YMCA facilities in Phoenix, Arizona from May 2016 to March 2020. INTERVENTION: Participants were randomized to lifestyle intervention (INT) or usual care control (UCC). The 6-month INT included 1 d/wk of nutrition and health education and 3 d/wk of physical activity. UCC included 2 visits with a pediatric endocrinologist and a bilingual, bicultural registered dietitian to discuss diabetes risks and healthy lifestyle changes. MAIN OUTCOMES AND MEASURES: Insulin sensitivity, glucose tolerance, and weight-specific quality of life (YQOL-W) at 6- and 12-month follow-up. RESULTS: A total of 117 Latino youths (mean (SD) age, 14 (1) years; 47 (40.1%) girls) were included in the analysis. Overall, 79 were randomized to INT and 38 to UCC. At 6 months, the INT led to significant decreases in mean (SE) 2-hour glucose (baseline: 144 (3) mg/dL; 6 months: 132 (3) mg/dL; p = 0.002) and increases in mean (SE) insulin sensitivity (baseline: 1.9 (0.2); 6 months: 2.6 (0.3); p = 0.001) and YQOL-W (baseline: 75 (2); 6 months: 80 (2); p = 0.006), but these changes were not significantly different from UCC (2-hour glucose: mean difference, -7.2 mg/dL; 95% CI -19.7 to 5.3 mg/dL; p for interaction = 0.26; insulin sensitivity: mean difference, 0.1; 95% CI -0.7 to 0.9; p for interaction = 0.79; YQOL-W: mean difference, 6.3; 95% CI -1.1 to 13.7; p for interaction = 0.10, respectively). Both INT (mean (SE), -15 mg/dL (4.9); p = 0.002) and UCC (mean (SE), -15 mg/dL (5.4); p = 0.005) had significant 12-month reductions in 2-hour glucose that did not differ significantly from each other (mean difference, -0.3; 95% CI -14.5 to 14.1 mg/dL; p for interaction = 0.97). At 12 months, changes in mean (SE) insulin sensitivity in INT (baseline: 1.9 (0.2); 12 months: 2.3 (0.2); p = 0.06) and UCC (baseline: 1.9 (0.3); 12 months: 2.0 (0.2); p = 0.70) were not significantly different (mean difference, 0.3; 95% CI -0.4 to 1.0; p for interaction = 0.37). At 12 months, YQOL-W was significantly increased in INT (basline: 75 (2); 12 months: 82 (2); p < 0.001) versus UCC (mean difference, 8.5; 95% CI 0.8 to 16.2; p for interaction = 0.03). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, both INT and UCC led to similar changes in T2D risk factors among Latino youths with diabetes; however, YQOL-W was improved in INT compared with UCC. Diabetes prevention interventions that are effective in adults also appeared to be effective in high risk youths. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02615353.

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