The Federal Womens Study is an active clinical protocol aimed at recruiting 360 federal employees and contractors working in the Washington DC metropolitan area. One hundred and thirty-three women (50% African-American, 15% African immigrant and 35% white) have been screened (age 449, range 24-62 years). Among the enrolled women, the three groups are well matched by race/ethnicity for key socio-economic and demographic risk factors such as educational attainment, family history of diabetes and physical activity. Yet, we have already identified pre-diabetes in 33% of women (63% African-American, 6% African immigrant and 31% white). Therefore, this cohort reflects women who are at high risk for diabetes and heart disease and an excellent group in which to (a) test the efficacy of existing screening tests and (b) understand the pathophysiological progression of cardiometabolic disease. Since current cardiometabolic screening tests are centered on triglyceride and fasting glucose concentrations, we have employed two approaches to examine these risk factors. The Relationship of Triglycerides with Insulin Resistance, Hyperinsulinemia and Hepatic Fat Content This study will compare by race and continent of origin, the relationship of triglyceride concentration to key cardiometabolic risk factors, specifically diet, physical activity, insulin resistance (and hyperinsulinemia) and hepatic fat content. Consistent with our hypothesis, fasting triglyceride and triglyceride-rich lipoprotein concentrations are comparable in African immigrant and African American women and lower than in white women (P<0.01). Lower insulin sensitivity index (AI: 3.01.6 vs. AA: 2.51.6 vs. WW: 3.42.2 mU/L-1min-1, P=0.08) and greater acute insulin response to glucose (AI: 895528 vs. AA: 959790 vs. WW: 561429 mU/L, P=0.07) in African-American women. Using multi-variate linear models, we have shown that lower visceral and hepatic fat and lower insulin sensitivity were independently associated with fasting triglyceride-rich lipoprotein particles (adjR2=0.37, P<0.001). To further characterize the contribution of insulin secretion, insulin clearance and prandial gut factors to race/ethnic differences in hyperinsulinemia, we are comparing insulin response to oral, intravenous and prandial glucose loads. Preliminary findings suggest greater postprandial insulin concentrations relative to glucose response in both African immigrant and African American women. We plan to continue recruitment and look forward to an expanded dataset with interim analyses of our primary outcome variable, triglyceride concentration, with key modifying factors (diet composition, physical activity, insulin sensitivity indices and hepatic fat). These analyses should provide population-specific evidence which elucidate important pathophysiological pathways and ultimately lead to enhanced screening and diagnostic guidelines which have the potential to minimize diabetes related health disparities worldwide.