Diabetes and Heart Disease Risk in Blacks

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

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Abstract

This is a natural history, hypothesis-generating protocol designed to improve detection of diabetes and cardiometabolic disease in African descent populations. If our protocol generates new diagnostic paradigms, our data can be used for power analyses for new protocols and validations studies conducted in both the United States and Africa. As our work continues with traditional risk factors such as triglyceride (TG), insulin resistance, beta-cell function, body size, body fat content and distribution, we are actively searching for better diagnostic markers so the chances for early intervention and improved outcomes for African descent populations are achieved. Currently we are focusing on the identification in African descent populations: (1) best screening tests to detect pre-diabetes and diabetes; (2) the effect of SCT, HbC trait and G6PD deficiency on the performance of A1C as a diagnostic test for both prediabetes and diabetes; (3) the psychosocial determinants of diabetes and heart disease; (4) Influence of BMI on the balance between insulin resistance and beta-cell function. First: Best screening tests to detect prediabetes and diabetes in Africans. As A1C has a diagnostic sensitivity for the detection of abnormal glucose tolerance of <50% we have focused on alternative diagnostic tests such as: glycated albumin, fructosamine and fasting plasma glucose alone or in combination with A1C. In our recent publication in Diabetes Care, we demonstrated that A1C combined with glycated albumin markedly improved detection of abnormal glucose tolerance in nonobese Africans. Interestingly, the combination was ineffective in obese Africans. This has great implications for understanding the diversity in African descent populations. For African Americans, diabetes is more common than the obese. But emerging data demonstrates in Africans suggests that diabetes is more common in the nonobese and that is the group who would specifically benefit from the combined tests. In addition, we performed duplicate testing of glycated albumin and fructosamine (meaning same tests 1 week apart). We observed that diagnoses made by glycated albumin were highly reproducible but this was not the care for fructosamine. Therefore, allocation of resources could be improved by investing in glycated albumin rather than fructosamine. Second: Effect of HbC trait and G6PD deficiency on the diagnostic efficacy of A1C We have previously shown that Sickle Cell Trait does not impact the diagnostic efficacy of A1C. However, there is no published data on the effect of HbC trait on the diagnostic efficacy of A1C. This is because most studies either exclude people with HbC trait or combine them with SCT. So far in our study we have 14 people with HbC trait, 50 percent of whom had either prediabetes or diabetes. In this small sample the diagnostic sensitivity of A1C was 0% and the specificity was 100%. We need to continue to recruit participants. If this finding holds, areas of the world where the prevalence of both diabetes and HbC trait are high, will need to develop diagnostic alternatives to A1C. Recently, we identified one person who was homozygous and had HbCC. He was very athletic and healthy with normal glucose tolerance. But his A1C was spuriously reported by the laboratory as >15%. This re-enforces the need to find proper diagnostic tests for diabetes in the presence of hemoglobin C. Genetic studies suggest that G6PD deficiency may be associated with normal A1C levels even in the presence of hyperglycemia. This finding needs to be tested clinically. Therefore, we obtained permission to assay for G6PD deficiency to test this. In addition, we have engaged in a collaboration with NHGRI to further explore this possibility. Third: Psychosocial determinants of diabetes and heart disease in African immigrants Metabolic stress can be measured by allostatic load score equations. As TG levels are low in African descent populations despite obesity, and insulin resistance, we have discovered that the allostatic load score which are most effective in Africans include HDL levels but exclude TG levels. Working with the Africans in America cohort, we have found cardiometabolic health and stress are worse in Africans if they came to the United States as a refugee, emigrated after age 30 years, have three or more children, or lived in the United States for greater than 10 years. In addition, and as we published in the last year, we have found that Africans who immigrated before the age of 20, had better cardiometabolic health than Africans who immigrated at 20 years or older. We discovered that the majority of Africans who immigrated before the age of 20, identified as African, had African-born spouses, exercised, did not adopt adverse health behaviors, and actualized early life migration advantages, such as an American university education. Due to maintenance of cultural identity and actualization of opportunities in America, cardiometabolic health may be protected in Africans who immigrate before age 20. In short, immigrant health research must be cognizant of the age of immigration. We are now exploring the influence of perceived stress and sleep quality on the health of African immigrants. Fourth: The Influence of BMI on the balance between Insulin Resistance and Beta-cell Failure in African Descent Populations We are working on identifying if differences exist in the physiologic reasons for the development of abnormal glucose tolerance in African descent populations. In African Americans, the etiology may be obesity and insulin resistance. In African immigrants the reason for abnormal glucose tolerance is more often beta-cell failure without obesity than insulin resistance. In short, our research is suggesting that diagnostic and treatment paradigms will need to be modified according to the specific African descent population of origin. Overall, there is great public health significance to our work. Our research should lead to results which improve screening paradigms for diabetes, convert undiagnosed diabetes into diagnosed diabetes and decrease the rate of complications in African descent populations worldwide.