MECHANISMS OF NOCTURNAL HYPERTENSION IN TYPE 1 DIABETES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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一个统一的模式，即最初无症状，肾脏、心血管和自主神经功能正常。肾脏疾病的进展以夜间高血压和微量白蛋白尿（MA）为特征。这些变化随后在ESRD发生之前发展为明显的高血压和蛋白尿。健康个体在夜间的血压通常比白天下降约10-25%。1型糖尿病患者的一个有趣特征是血压失去了正常的昼夜变化，血压在夜间不下降。1型糖尿病患者夜间高血压的病因被认为是健康个体通常存在的交感神经-迷走神经平衡昼夜变化的丧失或衰减。健康个体的昼夜交感-迷走神经轴似乎是通过儿茶酚胺的昼夜释放来控制的，目前的证据表明，这种释放可能受到循环褪黑激素水平的调节。迄今为止，关于1型糖尿病患者儿茶酚胺和褪黑素水平的证据有限。因此，如果1型糖尿病患者交感迷走神经轴的改变是夜间褪黑激素和儿茶酚胺释放水平改变的结果，那么问题就出现了。具体目的1：确定与无夜间高血压的1型糖尿病患者和健康对照组相比，伴有夜间高血压的1型糖尿病患者夜间褪黑激素释放水平是否有显著改变。具体目的2：检查这三组患者的交感神经-迷走神经平衡，以验证与无夜间高血压和健康对照的1型糖尿病患者相比，伴有夜间高血压的1型糖尿病患者夜间褪黑素分泌减少可能与儿茶酚胺释放增加和交感神经-迷走神经平衡改变有关的假设。具体目的3：确定补充褪黑激素是否能显著改变伴有夜间高血压的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.