Diabetes and Heart Disease Risk in Blacks

黑人的糖尿病和心脏病风险

• 批准号: 10253728
• 负责人: Anne Sumner
• 金额: $ 119.68万
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10253728
• 关键词: Adult; Africa; Africa South of the Sahara; African; African American; Age; Americas; Area; Athletic; Authorization documentation; Beta Cell; Biological Assay; Body fat; Caring; Child; Clinical; Data; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic tests; Disease; Early Intervention; Enrollment; Equation; Equilibrium; Etiology; Failure; Fructosamine; G6PD gene; Genetic study; Glucosephosphate Dehydrogenase Deficiency; Goals; Health; Heart Diseases; Hemoglobin C; High Density Lipoproteins; Hyperglycemia; Immigrant; Insulin Resistance; Laboratories; Lead; Measures; Metabolic stress; Methods; Natural History; Non obese; Obesity; Patient Recruitments; Performance; Persons; Physiological; Population; Prediabetes syndrome; Prevalence; Preventive Intervention; Protocols documentation; Public Health; Publications; Publishing; Refugees; Reporting; Reproducibility; Research; Research Design; Resource Allocation; Risk Factors; Sampling; Sickle Cell Trait; Specificity; Stress; Testing; Triglycerides; United States; Work; allostatic load; cardiometabolism; cohort; design; diagnostic biomarker; epidemiology study; fasting plasma glucose; glucose tolerance; glycosylated serum albumin; health disparity; heart disease risk; improved; improved outcome; novel diagnostics; novel strategies; power analysis; psychosocial; recruit; screening; trait; validation studies

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 and body fat content and distribution, we are actively searching for better diagnostic markers so the chances for early intervention and improved outcomes 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 A1Cs performance of 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 Failure 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. 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. In the last year, we did not identify anyone with HbC trait but did find 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. Our current sample suggests this may be true but continued consecutive testing of African immigrants should provide a more definitive answer. 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. In the last year 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. We are now examining the cardiometabolic effects in adulthood of coming to the United States as child versus arriving in the United States as adult. 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 may be beta-cell failure without obesity or insulin resistance. If further recruitment and analyses confirms this, then diagnostic and treatment paradigms will need to be modified according to the 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.

这是一种自然史，假设生成方案，旨在改善非洲血统种群中糖尿病和心脏代谢疾病的检测。如果我们的协议产生新的诊断范例，我们的数据可用于用于在美国和非洲进行的新协议和验证研究的功率分析。随着我们的工作继续进行传统危险因素，例如甘油三酸酯（TG），胰岛素抵抗和体内脂肪含量和分配，我们正在积极寻找更好的诊断标记，因此可以实现早期干预和改善结果的机会。 目前，我们专注于非洲血统人群的鉴定：（1）最佳筛查测试以检测糖尿病前和糖尿病； （2）SCT，HBC性状和G6PD缺乏对糖尿病前和糖尿病诊断测试的A1CS性能的影响； （3）糖尿病和心脏病的社会心理决定因素； （4）BMI对胰岛素抵抗和β细胞衰竭之间平衡的影响 最佳筛查测试可检测非洲人的前糖尿病和糖尿病。 由于A1c具有诊断敏感性，可用于检测<50％的异常葡萄糖耐量，因此我们专注于替代性诊断测试，例如：糖化白蛋白，果糖和空腹血糖单独或与A1C结合使用。在我们最近在糖尿病护理中的出版物中，我们证明了A1C与糖化白蛋白相结合，显着改善了非肥胖非洲人对异常葡萄糖耐受性的检测。有趣的是，这种组合在肥胖非洲人中无效。这对理解非洲血统种群的多样性具有很大的影响。对于非裔美国人来说，糖尿病比肥胖更普遍。但是在非洲人中表明的新兴数据表明，糖尿病在非肥胖症中更为常见，这是该群体将特别受益于合并测试。此外，我们对糖化白蛋白和果糖胺进行了重复测试（相距1周，这意味着相同的测试）。我们观察到糖化白蛋白做出的诊断是高度可重复的，但这并不是果糖的关注。因此，通过投资糖化白蛋白而不是果糖的投资可以改善资源的分配。 HBC性状和G6PD缺乏对A1C诊断功效的影响 我们以前已经表明，镰状细胞性状不会影响A1C的诊断功效。 但是，没有关于HBC特征对A1C诊断功效的影响的公开数据。这是因为大多数研究要么排除具有HBC特征的人，要么将其与SCT结合在一起。到目前为止，在我们的研究中，我们有14人患有HBC特征，其中50％患有糖尿病前期或糖尿病。在这个小样本中，A1C的诊断灵敏度为0％，特异性为100％。我们需要继续招募参与者。如果这一发现成立，那么世界上糖尿病和HBC特征的患病率很高的地区将需要开发A1C的诊断替代方案。在过去的一年中，我们没有确定任何具有HBC特征的人，而是找到了一个纯合子和HBCC的人。他的运动能力非常健康，具有正常的葡萄糖耐受性。但是他的A1C被假冒的实验室据报道> 15％。这加剧了在存在血红蛋白的情况下找到适当的糖尿病诊断测试的需求。 遗传研究表明，即使存在高血糖，G6PD缺乏也可能与正常的A1C水平有关。该发现需要在临床上进行测试。因此，我们获得了分析G6PD缺乏症的许可以对此进行测试。我们当前的样本表明这可能是正确的，但是对非洲移民的连续测试应提供更确定的答案。 非洲移民的糖尿病和心脏病的社会心理决定因素 代谢应力可以通过同层负荷评分方程来测量。尽管尽管肥胖和胰岛素抵抗，但由于非洲血统种群的TG水平较低，我们发现在非洲人中最有效的同种异体负载评分包括HDL水平，但不包括TG水平。 去年，与非洲人队列的非洲人合作，如果非洲人以难民的身份来到美国，他们发现心脏代谢的健康和压力会更严重，在30岁以后移民，有三个或更多的孩子或在美国生活了10年以上。 现在，我们正在研究成年后的成年时代的心脏代谢效应，因为儿童而不是成年。 BMI对非洲血统种群胰岛素抵抗与β细胞衰竭之间平衡的影响 我们正在努力确定非洲血统种群异常葡萄糖耐受性的生理原因是否存在差异。在非裔美国人中，病因可能是肥胖和胰岛素抵抗。在非洲移民中，异常葡萄糖耐受性的原因可能是β细胞衰竭而没有肥胖或胰岛素抵抗。如果进一步招募和分析证实了这一点，则需要根据原籍人群来修改诊断和治疗范例。 总体而言，我们的工作具有很大的公共卫生意义。我们的研究应导致改善糖尿病的筛查范例，将未诊断的糖尿病转化为被诊断的糖尿病，并降低全球非洲血统种群的并发症率。