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: 7500086
• 负责人: DANIEL BATLLE
• 金额: $ 53.95万
• 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/7500086
• 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（由申请人提供）：只有一小部分1型糖尿病患者，不到40%，会发展成肾病。在那些易患肾病的个体中，自然历史的特点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一般人群相似。然而，这些患者中的许多人在发展为微量白蛋白尿之前就发展为夜间高血压。然而，目前仅在有肾损害迹象（如微量白蛋白尿的存在）的情况下，才推荐使用ACE抑制剂进行早期药物干预。在微量白蛋白尿之前开始ACE治疗目前不推荐，因为它会导致大多数受试者过度治疗，而这些受试者永远不会出现微量白蛋白尿或显性肾病。然而，当微量白蛋白尿发生时，糖尿病的肾脏病变经常出现，许多患者进展为明显的临床肾病。因此，如果能够识别出易患微量白蛋白尿的患者，将是非常有益的，这样就可以对那些高危人群进行早期治疗。该研究的目的是证明，通过对“血压正常”、蛋白尿正常的1型糖尿病患者(即那些睡眠血压生理性下降钝化的患者（“非低血压者”）预先施用ACE抑制剂，有可能预防微量白蛋白尿的进展。这种方法在糖尿病的早期阶段，即在出现微量蛋白尿或高血压之前，具有很大的预防价值。因此，我们提出了一项新的试验，以夜间高血压为基础，对“血压正常”的1型糖尿病患者进行微量白蛋白尿一级预防。本研究的具体目的是：1)证明在夜间高血压患者（“非尿频者”）中，ACE抑制剂雷米普利的使用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（“不服用安慰剂者”）的微量白蛋白尿进展率高于服用安慰剂的“服用安慰剂者”。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舒张来评估内皮功能障碍是否先于1型糖尿病患者，特别是夜间高血压患者发生微量白蛋白尿。此外，这些研究将揭示长期ACE抑制对正常血压的1型糖尿病患者夜间高血压和内皮功能障碍的影响。