HYPOGLYCEMIA AND COUNTER-REGULATORY RESPONSES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在1型糖尿病儿童中，与低血糖相关的现象，如对低血糖的反调节激素反应和自主反应，尚未像成人那样广泛评价。本研究的主要目的是比较年幼糖尿病儿童低血糖期间发生反调节激素反应时的葡萄糖水平与年长糖尿病儿童发生的葡萄糖水平反调节激素反应。 本研究旨在比较T1 DM幼儿与青少年对血糖轻度和逐渐降低的反调节激素反应。这些研究将在每个DirecNet中心的专业人员的密切监督下进行，频繁的床旁血糖浓度监测将确保防止发生具有临床意义的低血糖。所有受试者将入住CRC，并在研究前一天晚上插入静脉输液管进行血样采集，以减轻研究当天早晨的压力。与钳夹或标准胰岛素输注研究（即，仅需要一次IV采血）相比，将简化研究程序并降低侵入性，方法是将入组限制在接受胰岛素泵治疗的受试者中，这些受试者将适度增加基础率以产生低血糖刺激。(1)特别重要的是要注意，一旦血糖水平福尔斯60 mg/dl以下，将采集血样，然后立即通过静脉注射外源性葡萄糖纠正低血糖。在我们最近的DirecNet研究中，（2）约25%的儿童和青少年在典型的夜间血糖水平低于60 mg/dl，当下午晚些时候进行运动时，这一比例上升至约50%。此外，轻度和重度低血糖的频率在学龄前儿童中显著高于年龄较大的儿童和青少年。这项安全、严格设计的研究将提供重要的新信息，说明反调节不足在极年幼T1 DM儿童低血糖风险增加中的作用。 本研究的第二个目的是获得关于低血糖期间幼儿和青少年真实的实时动态血糖监测仪准确性的非常重要的数据。实时连续葡萄糖传感系统有可能显著降低T1 DM青年患者的低血糖风险。DirecNet已经测试了动态血糖监测仪的准确性，包括Medtronic Minimed CGMS、Cygnus GlucoWatch G2 Biographer和Abbott Freestyle Navigator。在这些研究中，T1 DM儿童在CRC住院约26小时，期间每种器械佩戴1-2件，一次最多佩戴4件。这些研究中的每例受试者每30-60分钟从留置静脉导管中采集一次血样，用于在DirecNet中心实验室测量参考血糖水平。在当前方案中，我们将研究Medtronic Guardian RT连续监测系统。 该系统是实时连续血糖监测仪，在糖尿病儿童中具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.