PREVENTION OF DIABETIC NEPHROPATHY IN IDDM

这项提案要求支持一项临床研究，旨在 是否降低早期胰岛素的高滤过 依赖型糖尿病与血管紧张素II的抑制 转换酶将逆转微量白蛋白尿，防止 肾小球滤过率进行性下降 在其他有关胰岛素依赖型糖尿病的研究中也有记载。我们 目前有263例胰岛素依赖型糖尿病患者 糖尿病视网膜病变自然病史的纵向研究 由眼科。近70%的人 受试者没有常规临床可检测到的蛋白尿 程序。在这些没有蛋白尿的人中， 微量白蛋白尿的特征是白蛋白 定时尿液采集和个体的放射免疫分析 白蛋白排泄率超过15微克/分钟将 被随机分成两组。其中一组将是患有 早期微量白蛋白尿(15-80微克/分钟)和第二次 小组将包含那些有微量白蛋白排泄的个人 白蛋白含量从81微克到250微克不等 几分钟。没有人的血压高于140/85 或者正在接受降压治疗的人将被包括在内。 将两组随机分成一组 对照组和治疗组给予转化 酶抑制剂剂量为20毫克/天。微量白蛋白 排泄率将每三个月测量一次， 每六个月肾小球滤过率和评估 视网膜将每年更换一次。观察将会 在启动后的三年内完成 治疗。结果变量将是微量白蛋白排泄 GFR的变化和视网膜病变的严重程度的变化。 这项研究应该提供一个直接测试的假设， 早期糖尿病患者肾小球过度充盈在糖尿病发病中的作用 糖尿病发生的重要致病作用 肾病。

This proposal requests support for a clinical study designed to see whether lowering the hyperfiltration that occurs in early insulin dependent diabetes mellitus and inhibition of angiotensin II converting enzyme will reverse microalbuminuria and prevent the progressive decline in glomerular filtration rate that has been documented in other studies of insulin dependent diabetes. We have available 263 cases of insulin dependent diabetes presently in a longitudinal study of the natural history of diabetic retinopathy by the Department of Ophthalmology. Nearly 70 percent of the subjects do not have proteinuria detectable by routine clinical procedures. In these individuals without proteinuria, the rate of microalbuminuria will be characterized by an albumin radioimmunoassay of timed urine collections and those individuals with albumin excretion rates in excess of 15 micrograms/min will be randomized into two groups. One group will be patients with early microalbuminuria (15 to 80 micrograms/min) and the second group will contain those individuals with microalbumin excretion rates ranging between 81 and 250 micrograms of albumin per minutes. No individual with a blood pressure greater than 140/85 or who is receiving antihypertensive therapy will be included. Each of the two groups will be randomized into a treatment group and a control group and the treatment group given converting enzyme inhibitors at a level of 20 mg/day. Microalbumin excretion rates will be measured every three months and glomerular filtration rates every six months and assessment of retinal changes will be made on an annual basis. Observations will be made over a period of three years following initiation of treatment. Outcome variables will be microalbumin excretion rate, change in GFR and change in the severity of retinopathy. This study should provide a direct test of the hypothesis that the hyperprofusion of the glomeruli in early diabetes mellitus play an important pathogenetic role in the production of diabetic nephropathy.