Diabetes and Heart Disease Risk in Blacks

National Institute Of Diabetes And Digestive And Kidney Diseases

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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. With the oral glucose tolerance test (OGTT) as the diagnostic standard, A1C has a sensitivity for the detection of abnormal glucose tolerance of <50%. Therefore, we have focused on finding 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 immigrants living in the United States. In addition, we have collaborated with Dr. Andre Pascal Kengne from the Medical Research Council of South Africa, and made a similar finding in Mixed Race Ancestry population of Cape Town. Therefore, our work in African immigrants is informing research in sub-Saharan Africa. Interestingly, the combination of A1C and glycated albumin was ineffective in nonobese Africans. This has great implications for understanding the diversity in African descent populations. For African Americans, diabetes is more common than the obese than the nonobese. 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 case for fructosamine. Therefore, allocation of resources for both patient care and the design of epidemiologic studies could be improved by investing in glycated albumin rather than fructosamine (this finding will be published later this academic year). However, in the last year, we have started to look in a new direction. We have started to look at additional alternatives to the OGTT and have developed a Pastry Sugar Tolerance Test (PSTT). The advantages of the PSTT is that it is less expensive than the OGTT, A1C and glycated albumin. It can be prepared locally and our preliminary studies in 65 African immigrants suggest for the diagnosis of diabetes it is very reliable. Additional studies are underway in African Americans. 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 16 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 and our analyses is underway. 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, we have found that Africans who immigrated as children, had better cardiometabolic health than Africans who immigrated as adults. We discovered that the majority of Africans who immigrated as children, still identified as African rather than African Americans, 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. In addition, we have recently proven that perceived stress and sleep quality are adversely affected by low income. In doing this research we were able to validate the use of Cohens Perceived Stress Scale and the Pittsburgh Sleep Quality Index in African immigrants, even though these tools had not been developed in this population. In the last year we have started to evaluate the effect of discrimination on stress and risk for cardiometabolic disease in both African immigrants and African Americans. 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. Due to this difference in etiology of abnormal glucose tolerance in African Americans and African immigrants, we have proven that new diabetes prediction equations will have to be developed for African immigrants. 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.