HYPOGLYCEMIA AND COUNTER-REGULATORY RESPONSES

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。 在儿童1型糖尿病患者中，与低血糖相关的现象，如反调节激素反应和对低血糖的自主神经反应，还没有像成人那样得到广泛的评估。这项研究的主要目标将是比较糖尿病儿童低血糖期间发生逆调节激素反应的血糖水平与年龄较大的糖尿病儿童发生的血糖水平逆调节激素反应。 本研究旨在比较患有T1 DM的儿童和青少年对轻度和逐渐降低血糖的反调节激素反应。这些研究将在每个DirecNet中心的专业人员的密切监督下进行，频繁的床边血糖浓度监测将确保防止出现临床上明显的低血糖。所有受试者都将被送往CRC，并在研究前一晚插入静脉输液管进行血液采样，以减轻研究当天早上的压力。与夹式或标准的胰岛素输注研究(即只需要一次静脉采血)相比，研究程序将得到简化，并使侵入性更小，仅限于接受胰岛素泵治疗的受试者，这些受试者的基础频率将略有提高，以产生降血糖刺激。(1)特别重要的是要注意，一旦血糖水平降至60毫克/分升以下，将采集血样，然后通过静脉注射外源性葡萄糖立即纠正低血糖。在我们最近的DirecNet研究中，(2)~25%的儿童和青少年在一个典型的夜晚血糖水平低于60 mg/dl，而当下午晚些时候开始锻炼时，这一比例上升到约50%。此外，学龄前儿童轻度和严重低血糖的发生率明显高于年龄较大的儿童和青少年。这项安全和严格设计的研究将提供重要的新信息，说明不充分的反调节对T1 DM儿童低血糖风险增加的作用。 这项研究的第二个目的是获得关于儿童和青少年低血糖期间实时连续血糖监测的准确性的非常重要的数据。实时连续血糖检测系统提供了显著降低青年T1 DM患者低血糖风险的潜力。DirecNet已经测试了包括Medtronic Minimed CGMS、Cygnus GLucoWatch G2传记和雅培Freestyle Navigator在内的连续血糖监测仪的准确性。在这些研究中，患有T1 DM的儿童被纳入CRC约26小时，在此期间，他们一次佩戴多达4个设备，每个设备1-2个。这些研究中的每个受试者都每隔30-60分钟从留置静脉导管采集一次血液样本，用于在DirecNet中心实验室测量参考血糖水平。在目前的方案中，我们将研究美敦力卫士RT连续监测系统。该系统是实时、连续的血糖监测仪，在糖尿病儿童中有相当大的应用前景。

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. In children with Type 1 diabetes, the phenomena associated with hypoglycemia such as counter-regulatory hormone responses and autonomic responses to hypoglycemia have not been evaluated as extensively as in adults. The primary objective of this study will be to compare the glucose level at which counter-regulatory hormone responses occur during hypoglycemia in young children with diabetes, with the glucose level counter-regulatory hormone responses that occur in older children with diabetes. The present study is being undertaken to compare counter-regulatory hormone responses to a mild and gradual reduction in plasma glucose in young children with T1DM versus responses in adolescents. The studies will be performed under the close supervision of the professional staff of each DirecNet center and frequent bedside monitoring of plasma glucose concentrations will ensure that clinically significant hypoglycemia is prevented from developing. All subjects will be admitted to the CRC and have an IV line for blood sampling inserted on the evening prior to study to reduce stress on the morning of the study. The study procedure will be simplified and made less invasive in comparison to a clamp or standard insulin infusion study (i.e. only the one IV for blood sampling will be needed) by limiting enrollment to insulin pump-treated subjects who will have their basal rates modestly increased to produce the hypoglycemic stimulus.(1) It is particularly important to note that once the blood glucose level falls below 60 mg/dl, a blood sample will be obtained and hypoglycemia will then be immediately corrected by intravenous administration of exogenous glucose. In our recent DirecNet study,(2) ~25% of children and adolescents had plasma glucose levels below 60 mg/dl during a typical night and this rose to ~50% of subjects when there was antecedent exercise in the late afternoon. Moreover, the frequency of mild as well as severe hypoglycemia is substantially higher in pre-school children than in older children and adolescents. This safe and rigorously designed study will provide important new information regarding the role of inadequate counter-regulation on the increased risk of hypoglycemia in very young children with T1DM. A secondary aim of this study is to obtain very important data regarding the accuracy of real time continuous glucose monitors in young children and adolescents during hypoglycemia. Real-time continuous glucose sensing systems offer the potential to markedly lower the risk of hypoglycemia in youth with T1DM. DirecNet has tested the accuracy of continuous glucose monitors, including the Medtronic Minimed CGMS, Cygnus GlucoWatch G2 Biographer, and the Abbott Freestyle Navigator. In these studies, children with T1DM were admitted to the CRC for approximately 26 hours during which they wore 1-2 of each device, for as many as 4 devices at one time. Every subject in those studies had blood samples obtained every 30-60 minutes from an indwelling intravenous catheter for measurement of reference plasma glucose levels in the DirecNet Central Laboratory. In this current protocol, we will study the Medtronic Guardian RT continuous monitoring system. This system is real-time continuous glucose monitors that has considerable promise for use in children with diabetes.