Diabetes and Heart Disease Risk in Blacks

黑人的糖尿病和心脏病风险

• 批准号: 10922449
• 负责人: Anne Sumner
• 金额: $ 124.69万
• 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/10922449
• 关键词: Adult; Affect; Africa; Africa South of the Sahara; African; African American population; African ancestry; Age; American; Area; Athletic; Authorization documentation; Beta Cell; Biological Assay; Black Populations; Body Size; Body fat; Body mass index; Cardiometabolic Disease; Caring; Cell physiology; Child; Clinical; Collaborations; Data; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostic Sensitivity; Diagnostic tests; Discrimination; Early Intervention; Education; Emigrations; Enrollment; Equation; Equilibrium; Etiology; Exclusion; Exercise; Failure; Fructosamine; G6PD gene; Genetic study; Glucosephosphate Dehydrogenase Deficiency; Goals; Health; Health behavior; Heart Diseases; Hemoglobin C; Heterogeneity; High Density Lipoproteins; Hyperglycemia; Immigrant; Immigration; Insulin Resistance; Investments; Laboratories; Life; Low income; Maintenance; Measures; Medical Research; Metabolic stress; Methods; National Human Genome Research Institute; Natural History; Non obese; OGTT; Obesity; Patient Care; Patient Recruitments; Performance; Persons; Physiological; Pittsburgh Sleep Quality Index; Population; Prediabetes syndrome; Prevalence; Protocols documentation; Public Health; Publications; Publishing; Race; Reduce health disparities; Refugees; Reporting; Reproducibility; Research; Research Design; Resource Allocation; Risk Factors; Sampling; Sickle Cell Trait; South Africa; Specificity; Spouses; Stress; Testing; Triglycerides; United States; Universities; Work; allostatic load; cardiometabolic risk; cardiometabolism; cohort; design; detection sensitivity; diagnostic biomarker; epidemiology study; fasting plasma glucose; glucose tolerance; glycosylated serum albumin; heart disease risk; improved; improved outcome; migration; novel diagnostics; perceived stress; power analysis; preventive intervention; psychosocial; screening; sleep quality; social determinants; sugar; tool; 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, 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.

这是一个自然史、假设生成方案，旨在改善非洲人后裔人群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，我们的数据可用于新协议的功效分析以及在美国和非洲进行的验证研究。随着我们继续研究甘油三酯 (TG)、胰岛素抵抗、β 细胞功能、体型、体脂肪含量和分布等传统风险因素，我们正在积极寻找更好的诊断标记物，以便为非洲裔人群实现早期干预和改善结果的机会。 目前我们的重点是非洲裔人群的识别：（1）最佳筛查测试来检测糖尿病前期和糖尿病； (2) SCT、HbC 特征和 G6PD 缺乏对 A1C 作为糖尿病前期和糖尿病诊断测试性能的影响； (3) 糖尿病和心脏病的社会心理决定因素； (4)BMI对胰岛素抵抗与β细胞功能平衡的影响。 第一：检测非洲人糖尿病前期和糖尿病的最佳筛查测试。 以口服葡萄糖耐量试验（OGTT）为诊断标准，A1C检测糖耐量异常的敏感性<50%。因此，我们专注于寻找替代诊断测试，例如：单独的糖化白蛋白、果糖胺和空腹血糖或与 A1C 组合。在我们最近在《糖尿病护理》杂志上发表的文章中，我们证明 A1C 与糖化白蛋白相结合可显着改善居住在美国的非肥胖非洲移民中糖耐量异常的检测。此外，我们与南非医学研究委员会的Andre Pascal Kengne博士合作，在开普敦的混血人群中也得到了类似的发现。因此，我们在非洲移民方面的工作正在为撒哈拉以南非洲的研究提供信息。 有趣的是，A1C 和糖化白蛋白的组合对非肥胖非洲人无效。这对于理解非洲人后裔的多样性具有重要意义。对于非裔美国人来说，糖尿病比肥胖者更常见，而不是非肥胖者。但新出现的数据显示，在非洲人中，糖尿病在非肥胖人群中更为常见，而这一群体将特别受益于联合测试。 此外，我们对糖化白蛋白和果糖胺进行了重复测试（意味着相隔 1 周进行相同的测试）。我们观察到，糖化白蛋白做出的诊断具有高度可重复性，但果糖胺的情况并非如此。因此，通过投资糖化白蛋白而不是果糖胺，可以改善患者护理和流行病学研究设计的资源分配（这一发现将在本学年晚些时候发表）。 然而，去年，我们开始寻找新的方向。我们已开始寻找 OGTT 的其他替代方案，并开发了糕点糖耐量测试 (PSTT)。 PSTT 的优点是比 OGTT、A1C 和糖化白蛋白便宜。它可以在当地准备，我们对 65 名非洲移民的初步研究表明，它对于糖尿病的诊断非常可靠。针对非裔美国人的更多研究正在进行中。 第二：HbC特征和G6PD缺乏对A1C诊断效能的影响 我们之前已经证明镰状细胞性状不会影响 A1C 的诊断功效。然而，目前还没有关于 HbC 特征对 A1C 诊断功效影响的公开数据。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 结合起来。到目前为止，我们的研究中有 16 名具有 HbC 特征的人，其中 50% 患有糖尿病前期或糖尿病。在这个小样本中，A1C 的诊断敏感性为 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，世界上糖尿病和 HbC 特征患病率均较高的地区将需要开发 A1C 的诊断替代方案。最近，我们确定了一名纯合子患有 HbCC 的人。他非常运动且健康，葡萄糖耐量正常。但实验室错误地报告他的 A1C 为 >15%。这再次强调了在血红蛋白 C 存在的情况下寻找适当的糖尿病诊断测试的必要性。 遗传学研究表明，即使存在高血糖，G6PD 缺乏也可能与正常 A1C 水平相关。这一发现需要进行临床测试。因此，我们获得了检测 G6PD 缺陷的许可来测试这一点。此外，我们还与 NHGRI 合作，进一步探索这种可能性，我们的分析正在进行中。 第三：非洲移民糖尿病和心脏病的社会心理决定因素 代谢应激可以通过稳态负荷评分方程来测量。尽管存在肥胖和胰岛素抵抗，但由于非洲裔人群的 TG 水平较低，我们发现对非洲人最有效的非稳态负荷评分包括 HDL 水平，但不包括 TG 水平。 我们与在美国的非洲人队列合作发现，如果非洲人以难民身份来到美国、30 岁后移民、有 3 个或更多孩子或在美国居住超过 10 年，他们的心脏代谢健康状况和压力会更差。 此外，我们发现，儿童时期移民的非洲人比成年移民的非洲人有更好的心脏代谢健康状况。我们发现，大多数小时候移民的非洲人仍然被认为是非洲人而不是非裔美国人，他们的配偶是非洲出生的，锻炼身体，没有采取不良的健康行为，并实现了早期移民的优势，例如接受美国大学教育。由于美国文化认同的维护和机会的实现，20岁之前移民的非洲人的心脏代谢健康可能会受到保护。简而言之，移民健康研究必须认识到移民的年龄。 此外，我们最近证明，低收入会对感知压力和睡眠质量产生不利影响。在这项研究中，我们能够验证科恩斯感知压力量表和匹兹堡睡眠质量指数在非洲移民中的使用，尽管这些工具尚未在该人群中开发出来。 去年，我们开始评估歧视对非洲移民和非裔美国人的压力和心脏代谢疾病风险的影响。 第四：BMI对非洲人后裔人群胰岛素抵抗和β细胞衰竭之间平衡的影响 我们正在努力确定非洲人后裔中葡萄糖耐量异常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，葡萄糖耐量异常的原因更多的是β细胞衰竭而不是肥胖，而不是胰岛素抵抗。由于非裔美国人和非洲移民葡萄糖耐量异常的病因学存在差异，我们已经证明必须为非洲移民开发新的糖尿病预测方程。简而言之，我们的研究表明，诊断和治疗模式需要根据特定的非洲人后裔群体进行修改。 总体而言，我们的工作对公共卫生具有重大意义。我们的研究结果应该能够改善糖尿病筛查模式，将未确诊的糖尿病转变为确诊的糖尿病，并降低全世界非洲人后裔的并发症发生率。

项目成果

Africans Who Arrive in the United States before 20 Years of Age Maintain Both Cardiometabolic Health and Cultural Identity: Insight from the Africans in America Study.

• DOI: 10.3390/ijerph17249405
• 发表时间: 2020-12-15
• 期刊: International journal of environmental research and public health
• 作者: Shoup EM;Hormenu T;Osei-Tutu NH;Ishimwe MCS;Patterson AC;DuBose CW;Wentzel A;Horlyck-Romanovsky MF;Sumner AE
• 通讯作者: Sumner AE

Variation in the Calculation of Allostatic Load Score: 21 Examples from NHANES.

• DOI: 10.1007/s40615-016-0246-8
• 发表时间: 2017-06
• 期刊: JOURNAL OF RACIAL AND ETHNIC HEALTH DISPARITIES
• 影响因子: 3.9
• 作者: Duong, Michelle T.;Bingham, Brianna A.;Aldana, Paola C.;Chung, Stephanie T.;Sumner, Anne E.
• 通讯作者: Sumner, Anne E.

Ethnic differences in triglyceride levels and high-density lipoprotein lead to underdiagnosis of the metabolic syndrome in black children and adults.

• DOI: 10.1016/j.jpeds.2009.04.049
• 发表时间: 2009-09
• 期刊: JOURNAL OF PEDIATRICS
• 影响因子: 5.1
• 作者: Sumner, Anne E

Stress Measured by Allostatic Load Score Varies by Reason for Immigration: The Africans in America Study.

• DOI: 10.1007/s40615-017-0368-7
• 发表时间: 2018-04
• 期刊: Journal of racial and ethnic health disparities
• 影响因子: 3.9
• 作者: Utumatwishima JN;Baker RL Jr;Bingham BA;Chung ST;Berrigan D;Sumner AE
• 通讯作者: Sumner AE

Age at Immigration and Kidney Function among Self-Identified Healthy Africans in the United States.

美国自我认定的健康非洲人的移民年龄和肾功能。

• DOI: 10.1007/s10903-014-0138-0
• 发表时间: 2014
• 期刊: Journal of immigrant and minority health / Center for Minority Public Health
• 作者: Ali,Mana;Mwendwa,DenéeT;Sims,Regina;Ricks,Madia;Sumner,AnneE
• 通讯作者: Sumner,AnneE