This protocol compares diabetes and heart disease risk in African-Americans (AA) and African immigrants. The AA cohort is known as TARA for: Triglyceride and Cardiovascular Risk in AA. The African immigrants are known as the: Africans in America cohort. The sample of AA participating appears to be representative of the AA population of the United States because the prevalence of obesity (43%), pre-diabetes (22%) and hypertension (21%) is similar to National Health and Nutrition Examination Survey data. However, there is no national data on diabetic or cardiac health of African immigrants. Therefore we are working to establish basic information. To explore risk for diabetes, we are relying not just on fasting glucose but are also on performing oral glucose tolerance tests and measuring A1C levels, fructosamine and glycated albumin levels. In performing these tests, we discovered that the prevalence of pre-diabetes and hypertension is twice as high in African than AA men. In addition, the rate of undiagnosed diabetes was 7% in African men vs. 0% in AA men. In contrast the rate of hypertension, diabetes and pre-diabetes are similar in African women and AA women. Identifying the reasons for why African immigrant men are less metabolically healthy than AA men has become a major focus of research in this protocol. To improve and then maintain good health in African men, it is essential to understand why pre-diabetes, diabetes and hypertension is occurring in African men even though African men are less obese, more likely to be non-smokers, more likely to be married and have similar educational levels and income as African-American men. As a next step we are now examining the effect of stress of immigration on diabetic and cardiovascular risk in African immigrants. We are measuring stress with the Allostatic Load Score. The specific immigration related factors we are age of immigration, duration of stay in the United States and reason for immigration. We are also working on determining whether A1C which has been recommended by the American Diabetes Association as a diagnostic test for diabetes, can replace the oral glucose tolerance test in people of African descent. A1C is a hemoglobin dependent test and African immigrants have a high prevalence of sickle cell trait (i.e. 10 to 40%) and hemoglobin C trait (i.e. 15% in West Africa). Therefore before widespread use of A1C as a diagnostic test for diabetes is instituted in Africa, validation is necessary. When we evaluated A1C in African immigrants, we found that the sensitivity was 50%. When the Africans are subdivided by presence or absence of variant hemoglobin, the sensitivity of A1C remained at 50%. Therefore, A1C is not be an ideal, single test in Africans and variant hemoglobins such as sickle cell trait and hemoglobin C trait are not the explanation for the low diagnostic efficacy of A1C. To achieve better diagnostic efficacy, we are in the process of examining alternatives such as fructosamine and glycated albumin as single tests and in combination with A1C. We have found that fasting glucose combined with A1C has a diagnostic sensitivity of 70%. But since obtaining a fasting sample can be problematic, we have also tested the combination of fructosamine and A1C and glycated albumin and A1C. Importantly we have found that in the detection of diabetes and prediabetes in Africans immigrants the combination of fructosamine and A1C is no better than A1C alone. However, the combination of A1C and glycated albumin had a diagnostic sensitivity of 72%. This is a big step forward because glycated albumin, while not yet widely available, is an inexpensive and easy test to set up and run. We are now working on establishing collaborations with physicians in several African countries to directly evaluate the efficacy of A1C and glycated albumn in Africa. The relationship of body size to cardiovascular and diabetes risk is another area of investigation. In our cohorts, the mean body mass index (BMI) in AA is 30.6 kg/m2 but only 26.4 kg/m2 in African immigrants. BMI is a mathematical method used to correct weight for height. Due to the broad range of BMI in the participants in this cohort, it is possible to evaluate the relationship of body size to insulin resistance, a major factor in the development of diabetes, and heart disease. We have found in AA men a waist circumference (WC) of 102 cm predicts both insulin resistance and obesity. This is in agreement with the National Cholesterol Education Program values for whites. But in African men, insulin resistance occurs at a much lower WC, specifically 92 cm. This difference between AA and African immigrant men, suggests that a single WC of risk does not apply to all African descent populations. The situation may be analogous to Asian populations, as the WC of risk is different in Chinese, Japanese and Asian Indians. In AA women we found that a WC of 98 cm predicted both insulin resistance and obesity and this WC of risk was similar in AA, African immigrant, Black South African and West African women. Therefore among populations of African descent, there may be less variation in women than men. However, as the WC of risk is 88 cm in white women, there is a large difference by race. Guidelines which screen for disease might be more effective if this was better appreciated and more fully understood. Elevated TG and low HDL are considered lipid hallmarks of insulin resistance. However while elevated TG is a marker of insulin resistance in whites, we have shown that TG is not a marker of insulin resistance in AA. Results from TARA were so impressive that the hypothesis that TG was not a marker of insulin resistance in African Americans was subsequently tested in NHANES data collected from 1999-2001. In this NHANES data set of whites, AA and Mexican Americans, the fact that TG was not a marker of insulin resistance was confirmed. However, TG was a powerful marker of insulin resistance in whites and Mexican Americans. Altogether this research on race differences in the relationship of TG to insulin resistance again demonstrates that to detect disease at time when intervention can affect outcome, there is a need to develop ethnic-specific guidelines. Recently the TG/HDL ratio at a level of >3.0 has been suggested to be a marker of insulin resistance. This is well established in whites. After demonstrating the TG/HDL ration did not work in AA, we tested the ratio in white South African women, Black South African women and West African women from Ghana and Nigeria. We found that while the ratio effectively predicted insulin resistance in the white women, it did not work in any group of women of African descent. Again demonstrating that findings related to insulin resistance in whites may not be applicable globally and systematic testing is necessary. Recently, it has been reported that low vitamin D levels may influence bone health as well as enhance risk for cardiometabolic disease. As people of African descent have lower vitamin D levels than whites, the adverse effect of low vitamin D in people of African descent may be magnified. Alternatively vitamin D may be sufficient at lower levels in people of African descent than whites. We have discovered that 50% of African immigrants have low vitamin D levels but less than 10% had evidence of deficiency. As vitamin D has a relatively narrow therapeutic whether it is wise to provide vitamin D supplementation to large numbers of African immigrants with vitamin D levels defined as low but no evidence of deficiency remains to be determined. In summary this protocol is dedicated to undertaking epidemiological research which defines relevant risk factors, improves cardiometabolic health, and prevents through early diagnosis, diabetes and heart disease in people of African descent globally.