MECHANISMS OF NOCTURNAL HYPERTENSION IN TYPE 1 DIABETES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖尿病是世界范围内终末期肾病(ESRD)的主要原因。在易感个体中，1型糖尿病患者肾脏微血管并发症的发展通常遵循统一的模式，最初是无症状的，肾脏、心血管和自主神经功能正常。肾脏疾病的进展则以夜间高血压和微量白蛋白尿(MA)的发展为特征。这些变化之后是在终末期肾病发展之前的显性高血压和蛋白尿的发展。 健康的人通常表现出夜间血压与白天血压相比下降约10%-25%。1型糖尿病患者的一个有趣特征是失去了血压的这种正常的昼夜变化，即血压在夜间不会下降。1型糖尿病患者夜间高血压的病因被归因于健康个体交感神经-迷走神经平衡昼夜节律变化的丧失或减弱。 健康个体的这种昼夜交感迷走轴似乎是通过儿茶酚胺的每日释放来控制的，目前的证据表明，这种释放可能受到循环中褪黑激素水平的调节。到目前为止，关于1型糖尿病患者中儿茶酚胺和褪黑素水平的证据有限。因此，问题是，1型糖尿病患者交感迷走轴的改变是否是夜间褪黑激素和儿茶酚胺释放水平改变的结果。 具体目的#1：确定有夜间高血压的1型糖尿病患者与无夜间高血压的1型糖尿病患者和健康对照组相比，夜间褪黑激素释放水平是否有显著变化。 具体目的#2：检测这三组患者的交感-迷走神经平衡，以检验与无夜间高血压的1型糖尿病患者和健康对照组相比，夜间褪黑素分泌减少可能与有夜间高血压的1型糖尿病患者儿茶酚胺释放增加和交感-迷走神经平衡改变有关的假设。 具体目标#3：确定补充褪黑激素是否显著改变有夜间高血压的1型糖尿病患者的夜间血压。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetes is the leading cause of end-stage renal disease (ESRD) world-wide. In susceptible individuals, the development of renal microvascular complications in type 1 diabetics often follows a uniform pattern which initially is asymptomatic with normal renal, cardiovascular and autonomic function. Progression of renal disease is then characterized by the development of nocturnal hypertension and microalbuminuria(MA). These changes are subsequently followed by the development of overt hypertension and proteinuria prior to the development of ESRD. Healthy individuals typically exhibit a fall in blood pressure at night in relation to their daytime blood pressure by approximately 10-25%. An interesting feature of type 1 diabetics is the loss of this normal circadian variation in blood pressure where blood pressure does not fall at night. The etiology of this nocturnal hypertension in type 1 diabetics has been ascribed to the loss or attenuation of the circadian changes in sympatho-vagal balance usually present in healthy individuals. This circadian sympatho-vagal axis in healthy individuals appears to be controlled through the diurnal release of catecholamines and current evidence suggests that this release may potentially be modulated by circulating levels of melatonin. To date, there is limited evidence regarding catecholamine and melatonin levels in type 1 diabetics. The question therefore arises if the altered sympatho-vagal axis of type 1 diabetics is the result of altered levels of nocturnal melatonin and catecholamine release. Specific Aim #1: To determine if type 1 diabetics with nocturnal hypertension have a significantly altered level of nocturnal melatonin release when compared to a group of type 1 diabetics without nocturnal hypertension and a group of healthy controls. Specific Aim #2: To examine the sympatho-vagal balance in these same 3 groups to test the hypothesis that decreased nocturnal melatonin secretion may be associated with increased catecholamine release and altered sympatho-vagal balance in type 1 diabetics with nocturnal hypertension as compared to type 1 diabetics without nocturnal hypertension and healthy controls. Specific Aim #3: To determine if supplemental administration of melatonin significantly changes nocturnal blood pressure when given to type 1 diabetics with nocturnal hypertension.