Nocturnal Hypertension and Prevention of Microalbuminuria in Type I Diabetics

I 型糖尿病患者的夜间高血压和微量白蛋白尿的预防

• 批准号: 7289364
• 负责人: DANIEL BATLLE
• 金额: $ 53.49万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289364
• 关键词: Albumins; Angiotensin-Converting Enzyme Inhibitors; Animal Model; Attenuated; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Clinical; Complication; Coronary Arteriosclerosis; Deposition; Development; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathy; Disease; Dose; End Point; End stage renal failure; Event; Evolution; Excretory function; Exhibits; Frequencies; Functional disorder; Future; General Population; Hypertension; Impaired Renal Function; Individual; Institutes; Insulin-Dependent Diabetes Mellitus; Intervention; Invasive; Kidney; Kidney Diseases; Kidney Failure; Lesion; Mediating; Microalbuminuria; Natural History; Normal Range; Patients; Pattern; Persons; Phase; Physiological; Placebos; Prevalence; Prevention; Preventive; Primary Prevention; Proteinuria; Publishing; Ramipril; Rate; Reading; Renal function; Renin-Angiotensin System; Research Personnel; Risk; Risk Factors; Sleep; Staging; Surrogate Markers; Thinking; Time; Ultrasonography; Vasodilation; base; brachial artery; design; diabetic; falls; hypertension prevention; inhibitor/antagonist; interest; mortality; normotensive; novel; prevent; programs; type I diabetic; urinary

DESCRIPTION (provided by applicant): Only a fraction of persons with Type 1 diabetes, less than 40%, go on to develop nephropathy. In those individuals susceptible to nephropathy, the natural history is characterized by a fairly predictable pattern of events. When urinary albumin excretion is within the normal range, the prevalence of hypertension based on office blood pressure readings is similar to that in the general population. Many of these patients, however, develop nocturnal hypertension before the development of microalbuminuria. Yet, early pharmacological intervention with ACE inhibitors is currently recommended only after there is an indication of kidney damage, as reflected by the presence of microalbuminuria. Prior to microalbuminuria initiation of ACE therapy is currently not recommended because it would result in over-treatment of a majority of subjects who will never develop microalbuminuria or overt nephropathy. By the time that microalbuminuria develops, however, the renal lesions of diabetes are often present and many patients progress to overt clinical nephropathy. It would therefore be greatly beneficial if one could identify those patients susceptible to develop microalbuminuria, so that therapy could be instituted early for those individuals at high risk. The proposed study is aimed at demonstrating that it is possible to prevent the progression to microalbuminuria by the preemptive administration of an ACE inhibitor to "normotensive", normoalbuminuric subjects with type 1 diabetes targeted on the basis of nocturnal hypertension, i.e. those in whom the physiologic fall in sleep blood pressure is blunted ("non-dippers"). This approach would be of great preventative value at a very early stage in the course of diabetes, i.e. prior to the development of either microalbuminuria or hypertension. Thus, we propose a novel trial of primary prevention of microalbuminuria in "normotensive" type 1 diabetes targeted on the basis of nocturnal hypertension. The specific aims of this study are: 1) to demonstrate that in subjects with nocturnal hypertension ("non- dippers"), the administration of the ACE inhibitor, ramipril, will decrease the rate of development microalbuminuria. 2) To demonstrate that progression to microalbuminuria in subjects with nocturnal hypertension, "non-dippers", treated with placebo is higher than in "dippers" also treated with placebo. In addition, these studies will provide novel information as to whether endothelial dysfunction, assessed by brachial artery flow mediated vasodilation antedates microalbuminuria in subjects with Type 1 diabetes, particularly in those with nocturnal hypertension. Moreover, these studies will reveal the impact of long-term ACE inhibition on nocturnal hypertension and endothelial dysfunction in normotensive type 1 diabetics.

描述(申请人提供)：只有一小部分1型糖尿病患者，不到40%，继续发展为肾病。在那些易患肾病的人中，自然病史的特征是相当可预测的事件模式。当尿白蛋白排泄在正常范围内时，基于办公室血压读数的高血压患病率与普通人群相似。然而，这些患者中的许多人在出现微量白蛋白尿之前就出现了夜间高血压。然而，目前建议仅在有肾脏损害的迹象后，才建议早期使用ACE抑制剂进行药物干预，这反映为微量白蛋白尿的存在。在微量白蛋白尿之前，目前不推荐开始ACE治疗，因为这会导致大多数受试者过度治疗，这些受试者永远不会出现微量白蛋白尿或临床肾病。然而，当微量白蛋白尿发展时，糖尿病的肾脏损害经常出现，许多患者进展为临床肾病。因此，如果能识别出那些易患微量白蛋白尿的患者，那么这将是非常有益的，这样就可以及早对那些高危患者进行治疗。这项拟议的研究旨在证明，可以通过先发制人地给予血管紧张素转换酶抑制剂来预防微量白蛋白尿的进展，这些受试者是以夜间高血压为基础的1型糖尿病患者，即那些睡眠血压生理性下降的人(“非勺型”)，他们的血压“正常”。在糖尿病病程的非常早期，即在出现微量白蛋白尿或高血压之前，这种方法将具有很大的预防价值。因此，我们提出了一项以夜间高血压为基础的针对血压正常的1型糖尿病患者微量白蛋白尿一级预防的新试验。这项研究的具体目的是：1)证明在夜间高血压患者(“非勺型”)中，给予血管紧张素转换酶抑制剂雷米普利将降低微量白蛋白尿的发生率。2)为了证明夜间高血压患者进展为微量白蛋白尿，服用安慰剂的“非勺型”患者比服用安慰剂的“勺型”患者进展得更快。此外，这些研究将提供新的信息，即通过肱动脉血流介导的血管扩张来评估内皮功能障碍是否会提前1型糖尿病患者，特别是夜间高血压患者的微量蛋白尿。此外，这些研究将揭示长期抑制血管紧张素转换酶对血压正常的1型糖尿病患者夜间高血压和内皮功能障碍的影响。