Pathobiology of Prediabetes in A Bi-Racial Cohort

双种族队列中糖尿病前期的病理学

• 批准号: 7588751
• 负责人: SAMUEL DAGOGO-JACK, M.D., D.Sc.
• 金额: $ 52.18万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7588751
• 关键词: African American; Beta Cell; Body Composition; Body fat; Cardiovascular system; Caucasians; Caucasoid Race; Cell physiology; Communities; Data; Development; Diabetes Mellitus; Disease; Energy Metabolism; Ethnic group; Functional disorder; Future; Glucose; Impaired fasting glycaemia; Impairment; Incidence; Individual; Insulin; Intervention; Leptin; Lipoproteins; Mediator of activation protein; Metabolic; Metabolic Marker; Metabolic syndrome; Morbidity - disease rate; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Non-Insulin-Dependent Diabetes Mellitus; Parents; Participant; Pathogenesis; Persons; Physical activity; Population; Prediabetes syndrome; Prevalence; Preventive; Preventive Intervention; Primary Prevention; Prospective Studies; Public Health; Race; Reporting; Risk; Risk Marker; Socioeconomic Status; Staging; Testing; cardiovascular risk factor; cohort; diabetes prevention program; ethnic difference; follow-up; genetic analysis; glucose tolerance; health disparity; high risk; impaired glucose tolerance; improved; insulin secretion; insulin sensitivity; mortality; novel; offspring; programs; response; socioeconomics

This proposal is in response to ProgramAnnouncement Number PA-04-074, "Health Disparities inNIDDK Disease." In contrast to the widely reported ethnic differences in prevalence, the incidence of type 2 diabetes was surprisingly similar (~11%) among individuals from the different U.S. ethnic groups inthe Diabetes Prevention Program(DPP). Because DPP participants had impaired glucose tolerance (IGT) at baseline, the finding of similar incident diabetes rates led us to hypothesizethat ethnic disparities are initiated much earlier during the pathogenesis of type 2 diabetes than is commonly realized. We,therefore, propose to study ethnic disparities proximal to the stage of prediabetes (IGT and impaired fastingglucose {IFG}). We will compare the rates of progression from normal glucosetolerance (NGT) to prediabetes in 200 African-American and 200 Caucasian offspring of parents with type 2 diabetes. Compared with NGT subjects, persons with prediabetes (e.g., IGT) have a two-fold increased risk of fatal cardiovasculardisease (CVD). Yet, few prospective studies exist on the natural history, predictors, mechanisms, and mediatorsof progression from NGT to prediabetes in any population, and none in African-Americans. We arguethat focusing on this early period is of public health significance, because the IGT stage may already betoo late for complete reversal of metabolic and cardiovascular sequelae. In our proposed study, initially NGTsubjects at high risk for type 2 diabetes will undergo repeated metabolic assessments, including glucosetolerance, insulin sensitivity, beta cell function, adipocytokines, CVD risk markers,and socioeconomic and other pertinent endpoints for 5 years. DNAspecimens will be stored for future genetic analysis. The primary endpoint is progression from NGTto prediabetes. Secondaryendpoints include changes in caloricintake, physical activity, body composition, insulin sensitivity, insulin secretion, lipoproteins, adipocytokines, proinflammatory markers and other known or putative predictors of glycemic dysregulation. Bycomparing these endpoints between Progressorsand Nonprogressors and African-Americans vs. Caucasianswe hope to provide novel data on the natural history of prediabetes, and determine whether ethnic disparities are programmed during the transition from NGT to prediabetes. Increased understanding of the variousfactors that trigger the changefrom normal glucose to prediabetes would enable the discovery of early preventive interventions beforefull blown diabetes and its related complications become established. Furthermore, understanding howthese factors differ acrossethnic groups will improve our ability to better target preventive measuresin different communities.

该提议是对程序发出编号PA-04-074的回应，“健康差异Inniddk 疾病。与广泛报道的种族差异相反，2型的发生率 糖尿病在美国不同种族的个体中出奇相似（〜11％） 糖尿病预防计划（DPP）。因为DPP参与者在 基线，发现类似事件的糖尿病率的发现导致我们假设种族差异是 在2型糖尿病的发病机理期间，启动比通常实现的启动要早得多。因此，我们 提议研究邻近糖尿病阶段的种族差异（IGT和空腹葡萄糖受损 {IFG}）。我们将比较从正常糖固化（NGT）到200 非裔美国人和200种糖尿病父母的白种人后代。与NGT相比 受试者，患有糖尿病前期的人（例如，IGT）有两倍的致命心脉管疾病风险 （CVD）。然而，很少有关于自然史，预测因素，机制和介体的前瞻性研究 在任何人群中，从NGT到糖尿病前期的进展，在非裔裔裔人中都没有。我们吵架 专注于这个早期具有公共卫生意义，因为IGT阶段可能已经迟到了 为了完全逆转代谢和心血管后遗症。在我们提出的研究中，最初是 2型糖尿病的高风险将经过重复的代谢评估，包括葡萄糖素降低， 胰岛素敏感性，β细胞功能，脂肪细胞因子，CVD风险标记以及社会经济和其他 相关端点5年。 DNASPECIPENS将存储用于将来的遗传分析。主要 终点是从糖尿病到糖尿病前的进展。次要点包括卡洛克塔克的变化， 体育活动，身体成分，胰岛素敏感性，胰岛素分泌，脂蛋白，脂肪细胞因子， 血糖失调的促炎标记和其他已知或推定的预测因子。临时 这些终点与非洲裔美国人与白种人的希望之间的终点 提供有关糖尿病前期自然史的新颖数据，并确定种族差异是否是 在从NGT到糖尿病前期的过渡期间进行了编程。 对各种因素的了解增加了从正常葡萄糖到糖尿病的变化 将在饱受全面的糖尿病及其相关之前发现早期的预防干预措施 并发症已建立。此外，了解霍瓦的因素在整个种族之间有所不同 小组将提高我们更好地针对不同社区的预防措施的能力。