Central Obesity and Albumin Excretion in Type 1 Diabetes

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，但许多患者仍然 糖尿病肾病（diabetic nephropathy，DN）是导致ESRD的主要原因。 心血管疾病是死亡的主要原因，风险开始加速， 微量白蛋白尿中心性肥胖综合征，这似乎是目前在一些 1型糖尿病患者和许多2型糖尿病患者， CVD和白蛋白排泄率（AER）升高。 该提案将定义腹腔内脂肪（IAF）的作用， 肾素-血管紧张素系统（RAS）在AER升高中的作用， 糖尿病受试者血脂异常的观察性横断面研究 一个亚群（三个明尼苏达队列和西雅图队列）的研究 流行病学干预和并发症研究以及 超重受试者的独立招募干预性体重减轻研究 患有1型糖尿病此外，人口研究将检查频率 G-6A血管紧张素原变体在高血压和非高血压受试者中的 (HTN)AER升高。 本项目的具体目标是：（1）表征RAS及其 与AER、性别和IAF（通过腹部CT测量）升高的关系， 1型糖尿病受试者;（2）确定IAF， 1型糖尿病受试者的中心性肥胖相关血脂异常、RAS和AER 糖尿病;（3）确定G-6A单倍型亚类的频率， 1型糖尿病患者，并确定这些 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 受试者在强化治疗期间体重增加的前四分位数 糖尿病控制和并发症试验。 这些研究将定义以下关系的潜在机制： 中心性肥胖和DN的早期阶段，提供适用于 2型糖尿病和HTN患者。

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.