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: 6736344
• 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/6736344
• 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.

描述（改编自应用程序） 在糖尿病患者中，微量白蛋白尿可预测终末期肾病 （ESRD）和心血管疾病（CVD）。尽管取得了进展，许多患者仍然 进展为 ESRD 和糖尿病肾病 (DN) 是 ESRD 的主要原因。 CVD 是导致死亡的主要原因，并且风险开始加速 微量白蛋白尿。中心性肥胖综合症，似乎存在于某些 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，会增加患 CVD 和白蛋白排泄率 (AER) 升高。 该提案将定义腹内脂肪 (IAF) 的作用和 肾素-血管紧张素系统 (RAS) 在 AER 升高和 通过横断面观察观察糖尿病患者的血脂异常 对亚人群（明尼苏达州的三个队列和西雅图队列）的研究 流行病学干预和并发症研究和 独立招募的超重受试者介入减肥研究 患有 1 型糖尿病。此外，人口研究将检查频率 患有和不患有高血压的受试者中 G-6A 血管紧张素原变体的影响 (HTN) 和 AER 升高。 该项目的具体目标是：（1）描述RAS及其特征 与 AER 升高、性别和 IAF（通过腹部 CT 测量）的关系 患有 1 型糖尿病的受试者； (2) 定义IAF之间的关系， 1 型受试者中与中心性肥胖相关的血脂异常、RAS 和 AER 糖尿病; (3) 确定G-6A单倍型细分的频率 患有 1 型糖尿病的受试者并确定这些受试者之间的关联 HTN 和 AER 的单倍型； (4) 比较 G-6A AGT 的频率 舒张压最高和最低四分位数的基因型 在强化治疗期间体重增加最高四分之一的受试者 糖尿病控制和并发症试验。 这些研究将定义之间关系的潜在机制 向心性肥胖和 DN 的早期阶段，提供适用于的见解 一些患有 2 型糖尿病和高血压的受试者。