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: 7081734
• 负责人: SAMUEL DAGOGO-JACK, M.D., D.Sc.
• 金额: $ 58.88万
• 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/7081734
• 关键词: African American; anthropometry; biomarker; blood tests; body composition; body physical activity; caloric dietary content; cardiovascular disorder; caucasian American; clinical research; diabetes risk; glucose tolerance; glucose tolerance test; health disparity; human population study; human subject; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; pancreatic islet function; pathologic process; questionnaires; racial /ethnic difference; socioeconomics

DESCRIPTION (provided by applicant): This application is in response to Program Announcement Number PA-04-074, "Health Disparities in NIDDK 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 in the Diabetes Prevention Program (DPP). Because DPP participants had impaired glucose tolerance (IGT) at baseline, the finding of similar incident diabetes rates led us to hypothesize that 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 fasting glucose {IFG}). We will compare the rates of progression from normal glucose tolerance (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 cardiovascular disease (CVD). Yet, few prospective studies exist on the natural history, predictors, mechanisms, and mediators of progression from NGT to prediabetes in any population, and none in African-Americans. We argue that focusing on this early period is of public health significance, because the IGT stage may already be too late for complete reversal of metabolic and cardiovascular sequelae. In our proposed study, initially NGT subjects at high risk for type 2 diabetes will undergo repeated metabolic assessments, including glucose tolerance, insulin sensitivity, beta cell function, adipocytokines, CVD risk markers, and socioeconomic and other pertinent endpoints for 5 years. DNA specimens will be stored for future genetic analysis. The primary endpoint is progression from NGT to prediabetes. Secondary endpoints include changes in caloric intake, physical activity, body composition, insulin sensitivity, insulin secretion, lipoproteins, adipocytokines, proinflammatory markers and other known or putative predictors of glycemic dysregulation. By comparing these endpoints between Progressors and Nonprogressors and African-Americans vs. Caucasians we 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 various factors that trigger the change from normal glucose to prediabetes would enable the discovery of early preventive interventions before full blown diabetes and its related complications become established. Furthermore, understanding how these factors differ across ethnic groups will improve our ability to better target preventive measures in different communities.

描述（由申请人提供）：此申请响应计划公告编号PA-04-074，“ NIDDK病的健康差异”。与广泛报道的种族差异相反，在糖尿病预防计划（DPP）中，美国不同族裔群体中2型糖尿病的发生率令人惊讶地相似（〜11％）。由于DPP参与者在基线时降低了葡萄糖耐量（IGT），因此发现类似的入射糖尿病率的发现使我们假设在2型糖尿病的发病机理期间，族裔差异比通常实现的族裔差异要早得多。因此，我们建议研究邻近糖尿病阶段的种族差异（IGT和禁食葡萄糖{IFG}）。我们将比较从正常的葡萄糖耐量（NGT）到200个非裔美国人和200个糖尿病父母的白种人后代的糖尿病前期的进展率。与NGT受试者相比，患有糖尿病前期患者（例如IGT）的人患致命心血管疾病（CVD）的风险增加了两倍。然而，很少有关于自然历史，预测因素，机制和介体从NGT到糖尿病前期糖尿病前期的前瞻性研究，而在非裔美国人中则没有。我们认为，关注早期时期具有公共卫生意义，因为IGT阶段可能已经为时已晚，无法完全逆转代谢和心血管后遗症。在我们提出的研究中，最初对2型糖尿病风险高的NGT受试者将经过反复的代谢评估，包括葡萄糖耐受性，胰岛素敏感性，β细胞功能，脂肪细胞因子，CVD风险标志物以及社会经济和其他相关端口已有5年了。 DNA标本将存储用于将来的遗传分析。主要终点是从NGT到糖尿病前的进展。次要终点包括热量摄入，体育活动，身体成分，胰岛素敏感性，胰岛素分泌，脂蛋白，脂蛋白，脂肪细胞因子，促炎标记物以及血糖失调的其他已知或推定的预测因子。通过比较进度者与非焦点与非裔美国人与高加索人之间的这些终点，我们希望提供有关糖尿病前期自然历史的新颖数据，并确定在从NGT到糖尿病群的过渡期间是否对种族差异进行了编程。对触发从正常葡萄糖变为前糖尿病的变化的各种因素的理解增加将使早期预防干预措施在完全爆破的糖尿病及其相关并发症建立之前。此外，了解这些因素如何在各个种族中有何不同将提高我们更好地针对不同社区的预防措施的能力。