Diabetes and Heart Disease Risk in Blacks

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

This is a natural history, hypothesis-generating protocol designed to improve detection of diabetes and cardiometabolic disease across populations. If our protocol generates new diagnostic paradigms, our data can be used for power analyses for new protocols and validations. Our work continues with traditional risk factors including insulin resistance, beta-cell function, body size, body fat content and distribution and the social determinants of disease including stress, sleep, resilience and body image. In short, as we study risk factors for diabetes and cardiometabolic disease, we are actively searching for better diagnostic markers so the chances for early intervention and improved outcomes across populations. Currently we are focusing on identifying across populations: (1) best screening tests to detect pre-diabetes and diabetes including whether the 1-h OGTT can replace the more expensive 2-h OGTT; (2) the effect of SCT, Hemoglobin C 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). We are also developing 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. In addition, the International Diabetes Federation (IDF) has suggested that the OGTT, could be decreased from 2h to 1h. They recommended that the glucose threshold for 1h for the diagnosis of diabetes be 209 mg/dL. Within weeks of the publication by the IDF, we showed that the proper threshold for the diagnosis of diabetes in Africans was 183 mg/dL. This article was fast tracked for publication by the journal “Diabetes Research and Clinical Practice.” In the next phase of our research on figuring out how to make the 1-h OGTT effective across populations, we submitted a commentary to “Diabetes Research and Clinical Practice” which is under review, demonstrating that for the 1-h OGTT, sensitivity for the detection of glucose tolerance status, specifically prediabetes which is also call Intermediate hyperglycemia would be markedly improved if fasting glucose≥100 mg/dL was combined with 1-h ≥155 mg/dL, the current diagnostic standard. Second: Effect of G6PD deficiency on the diagnostic efficacy of A1C Genetic studies suggest that G6PD deficiency may be associated with normal A1C levels even when hyperglycemia is present. This finding needs clinical testing. 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. We have demonstrated that in the presence of G6PD deficiency, A1C is artefactually low. Therefore, A1C is a poor diagnostic test in all populations with a high rate of G6PD. Furthermore, we have made the important finding that to diagnose G6PD deficiency the clinical assay is better than genetic testing. This is true for two reasons. First, a genetic scan can miss rare G6PD variants if it is not included in the array. In addition, G6PD deficiency is X-linked. In heterozygous women, only the assay will provide information on whether the degree of G6PD deficiency is clinically significant. Third: Psychosocial determinants of diabetes and heart disease 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 without TG levels. 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 proven that perceived stress and sleep quality are adversely affected by low income. In doing this research we validated 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. We are now evaluating if the effect of stress, resilience or sleep disturbances differ across populations of African descent, specifically African immigrants and African Americans and if there is a differential effect of these factors on cardiometabolic disease. Body image preference is a new area of investigation and understanding body size preferences often reflects willingness to obtain a healthy body size. Cultural influences and expectations are important. Fourth: The Influence of BMI on the balance between Insulin Resistance and Beta-cell Failure in African Populations We are working on identifying if differences exist in the physiologic reasons for the development of diabetes. In African Americans, the etiology may be obesity and insulin resistance. In African immigrants the reason for diabetes is more often beta-cell failure without obesity or insulin resistance. Due to this difference in diabetes etiology in African Americans and African immigrants, we have proven that diabetes prediction equations will have to be developed for African immigrants. In short, our research diagnostic and treatment paradigms need to be modified according to the specific African descent population. Yet independent of baseline BMI and etiology of glucose pathophysiology, it is important to counsel African immigrants to avoid weight gain after arriving in the United States. Prevention of weight gain in the United States, may be the single most important step to avoid subsequent development of diabetes. 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, promote diabetes remission and decrease complications in African descent populations worldwide.