This project was funded by NIDDK (R01DK107532, 9/15/2016-8/31/2022, PI: Jinying Zhao). The objective of this project is to identify novel and sensitive type 2 diabetes (T2D) predictors that are specific to American Indians beyond classical T2D indicators. To achieve this, we will repeatedly measure concentrations of over 500 metabolites, including BCAAs, carbohydrates, hydroxyl acids, lipids, as well as gut microbial-derived metabolites, in fasting plasma (~5 yr apart) from normoglycemic participants followed >15 years. Putative metabolites will be replicated in an independent longitudinal sample of American Indians followed up to 16 years.