In contrast to the widely reported ethnic differences in prevalence, the incidence of type 2 diabetes was surprisingly similar (approximately 11%) among individuals from the different US ethnic groups in the Diabetes Prevention Program (DPP). Because DPP participants had impaired glucose tolerance (IGT) at baseline, we hypothesized that ethnic disparities are initiated at the pre-IGT stage during evolution of type 2 diabetes. The Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) is designed to test that hypothesis by tracking the natural history of early dysglycemia in a biracial cohort comprising offspring of parents with type 2 diabetes. The POP-ABC study has an enrollment target of 400 participants (200 African American, 200 Caucasian), aged 18-65 years, with at least 1 parent with type 2 diabetes. All subjects must have normal fasting glucose and/ or normal glucose tolerance, as determined by a 75-gram oral glucose tolerance test (OGTT). Subjects are recruited over approximately 3 years and followed for another 2 years, with repeated metabolic assessments. The latter include OCTT, body composition, indirect calorimetry, euglycemic clamp, beta cell function, and biochemistries. Repository specimens (DNA, RNA and proteome) are obtained for future studies. The primary outcome is the occurrence of prediabetes (ICT and/or impaired fasting glucose). The sample size provides 85% power to detect a hazard ratio of 1.75 between Black and White offspring in the primary outcome (alpha = .05). Secondary endpoints include behavioral, biochemical and socioeconomic predictors of dysglycemia. The POP-ABC study will elucidate the nosogeny of ethnic disparities in glucose dysregulation.