Central Obesity and Albumin Excretion in Type 1 Diabetes

1 型糖尿病中的中心性肥胖和白蛋白排泄

• 批准号: 6635363
• 负责人: SHALAMAR D SIBLEY
• 金额: $ 13.33万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6635363
• 关键词: albumins; clinical research; excretion; gender difference; genotype; human subject; insulin dependent diabetes mellitus; obesity; pathologic process; renin angiotensin system; weight gain

DESCRIPTION (adapted from the application) In subjects with diabetes, microalbuminuria predicts end-stage renal disease (ESRD) and cardiovascular disease (CVD). Despite gains, many patients still progress to ESRD and diabetic nephropathy (DN) is the leading cause of ESRD. CVD is the leading cause of death and risk begins to accelerate with microalbuminuria. Central obesity syndrome, which appears to be present in some subjects with type 1 diabetes and many subjects with type 2, increases risk of CVD and elevated albumin excretion rate (AER). This proposal will define the roles of intraabdominal fat (IAF) and the renin-angiotensin system (RAS) in the development of elevated AER and dyslipidemia in subjects with diabetes through an observational cross-sectional study of a subpopulation (three Minnesota cohorts and the Seattle cohort) of the Epidemiology Interventions and Complications Study and an independently-recruited interventional weight loss study of overweight subjects with type 1 diabetes. Additionally, population studies will examine frequencies of the G-6A angiotensinogen variants in subjects with and without hypertension (HTN) and elevated AER. The specific aims of the project are: (1) to characterize the RAS and its relationship to elevated AER, gender, and IAF (as measured by abdominal CT) in subjects with type 1 diabetes; (2) to define the relationship between IAF, central obesity-related dyslipidemia, RAS, and AER in subjects with type 1 diabetes; (3) to determine the frequency of the G-6A haplotype subdivisions in subjects with type 1 diabetes and determine the associations of those haplotypes with HTN and AER; and (4) to compare frequencies of the G-6A AGT genotype in the highest and lowest quartiles of diastolic blood pressures among subjects in the top quartile of weight gain on intensive therapy during the Diabetes Control and Complications Trial. These studies will define mechanisms underlying the relationship between central obesity and the earliest stages of DN, providing insights applicable to some subjects with type 2 diabetes and HTN.

说明(改编自应用程序) 在糖尿病患者中，微量白蛋白尿预示终末期肾病 (ESRD)和心血管疾病(CVD)。尽管取得了进展，许多患者仍然 进展到终末期肾病和糖尿病肾病是终末期肾病的主要原因。 心血管疾病是导致死亡的主要原因，风险开始加速 微量白蛋白尿。中心性肥胖综合征，这似乎存在于一些 患有1型糖尿病的受试者和许多患有2型糖尿病的受试者会增加罹患 CVD和白蛋白排泄率(AER)升高。 这项提议将定义腹内脂肪(IAF)和 肾素-血管紧张素系统(RAS)在AER升高和高血压发病中的作用 通过观察横断面研究糖尿病患者的血脂异常 对亚群(三个明尼苏达州队列和西雅图队列)的研究 流行病学干预措施及并发症研究 超重受试者自主招募的干预性减肥研究 患有1型糖尿病。此外，人口研究将检查频率 高血压患者与非高血压患者G-6A血管紧张素原基因变异的研究 (HTN)和升高的AER。 该项目的具体目标是：(1)确定RAS及其 AER、性别和IAF(腹部CT测量)升高的关系 1型糖尿病的受试者；(2)定义IAF、 1型受试者中心性肥胖相关的血脂异常、RAS和AER 糖尿病；(3)测定G-6A单倍型亚型在 1型糖尿病的受试者并确定它们之间的关联 与HTN和AER的单倍型；以及(4)比较G-6A AGT的频率 以下人群中舒张压最高和最低四分位数的基因 在强化治疗期间体重增加前四分位数的受试者 糖尿病控制和并发症试验。 这些研究将确定两者之间关系的潜在机制 中心性肥胖和糖尿病肾病的早期阶段，提供了适用于 一些2型糖尿病合并HTN的受试者。