PROJECT SUMMARY Obesity and type 2 diabetes (T2D) disparities among Latino children and adolescents represent some of the most significant public health challenges facing society. Inflammation is associated with beta-cell dysfunction and both are evident in obese youth with prediabetes. Lifestyle intervention is the primary approach to preventing or delaying onset of T2D and has been effective in improving the inflammatory milieu and beta-cell function. However, less is known about the effect of lifestyle intervention on specific pro- and anti- inflammatory mediators associated with beta-cell dysfunction in youth. Furthermore, the relationship between changes in pro- and anti-inflammatory mediators and changes in beta-cell function remains unexplored in obese youth. Knowledge regarding the mechanisms by which T2D risk mediators are improved is limited due to a lack of measurement of different anti-inflammatory mediators. Therefore, we propose a longitudinal study that will examine the effect of lifestyle intervention on pro- and anti-inflammatory mediators in 79 obese Latino youth with prediabetes as compared to a usual care control group of 38 obesity- and glycemia-matched Latino youth. Understanding how changes in pro- and anti-inflammatory markers relate to changes in beta-cell function is important to identify specific mechanisms that can be targeted in future studies. Therefore, this study will explore the association between changes in pro- and anti-inflammatory mediators and changes in beta-cell function in obese Latino youth with prediabetes. This proposal leverages the resources and infrastructure of an ongoing diabetes prevention study and builds upon a transdisciplinary team of mentors to address a critical gap in chronic disease prevention in obese Latino youth, age 12-16 years. This innovative approach is an essential first step in the development of lifestyle interventions aimed at targeting inflammatory mechanisms to assess changes in T2D risk in this high-risk population.