Prevention of Hypoglycemia and Associated Complications in Type 1 Diabetes

描述（由申请人提供）：强化治疗现在被接受为糖尿病的当前标准治疗。然而，强化治疗经常伴有低血糖，低血糖成为维持血糖控制的限制因素。在强化治疗期间，糖尿病患者由于胰岛素过量、葡萄糖利用过度（如运动）或碳水化合物摄入不足而发生低血糖。幼儿和青少年有许多生活方式特点，使他们特别容易发生低血糖。此外，频繁的低血糖可导致神经系统后遗症。以目前的家庭血糖监测能力，很难准确定义低血糖的真实发生率、持续时间和严重程度。最近，连续血糖监测（CGM）已成为一种更密切地检查血糖模式和确定低血糖特征的工具，因此可以制定预防低血糖的措施。最近的神经认知和神经成像研究表明，发育中的大脑可能特别容易受到低血糖的影响。对特定神经认知缺陷的理解需要在儿童和年轻人中进一步研究。低血糖及其后遗症的最佳预防需要近乎连续的识别和对当前血糖浓度的反应。因此，我们的主要目标是使用CGM检测低血糖的频率、严重程度和持续时间，然后进行随机对照试验（RCT），以确定实时CGM在7-24岁的年轻1型糖尿病（T1DM）患者中降低低血糖风险的能力。此外，我们将检查活动评估、饮食或两者同时干预的附加变量，以确定是否可以进一步降低低血糖。基线时，我们将在横断面研究中比较低血糖频率、严重程度和持续时间以及其他因素，如糖尿病发病年龄或持续时间，以及神经认知和神经影像学参数。我们将描述T1型糖尿病儿童和年轻人与正常对照的神经解剖学差异。我们中心参与了儿童糖尿病研究网络（DirecNet），这是一个成功的由NIH资助的5个儿科糖尿病中心组成的联盟，并建立了一个协调中心来研究T1型糖尿病儿童的低血糖。我们拥有良好的基础设施，训练有素的人员，高效的患者招募系统，以及高效完成方案的成功历史。

DESCRIPTION (provided by applicant): Intensive therapy is now accepted as the current standard of care in diabetes. However, intensive therapy is frequently complicated by hypoglycemia, which then becomes a limiting factor in maintaining glucose control. During intensive treatment, hypoglycemia occurs in patients with diabetes due to excess insulin, 'excess glucose utilization (e.g. exercise) or inadequate carbohydrate intake. Young children and adolescents have many lifestyle characteristics that make them particularly prone to hypoglycemia. In addition, frequent hypoglycemia may lead to neurological sequelae. With current home glucose monitoring capabilities it is difficult to accurately define the true incidence, duration and severity of hypoglycemia. Continuous glucose monitoring (CGM) has recently become available as a tool to more closely examine glucose patterns and defining characteristics of hypoglycemia, so that measures for prevention of hypoglycemia can be devised. Recent neurocognitive and neuro-imaging studies show that the developing brain may be particularly vulnerable to hypoglycemia. The understanding of specific neurocognitive deficits requires further studies in children and young adults. Optimal prevention of hypoglycemia and its sequelae requires near-continuous recognition and response to prevailing blood glucose concentrations. Hence, our major objective is to use CGM to detect the frequency, severity and duration of hypoglycemia and then carry out a randomized controlled trial (RCT) to determine the ability of real-time CGM to minimize the risk of hypoglycemia in young patients with type 1 diabetes (T1DM) ages 7-24. In addition we will examine added variables of intervention with activity assessment, diet or both, to determine if further reductions in hypoglycemia are achievable. At baseline, we will compare rates of hypoglycemia frequency, severity and duration and other factors, such as age at onset or duration of diabetes, with neurocognitive and neuroimaging parameters in a cross-sectional study. We will characterize neuroanatomical differences in children and young adults with T1 DM, vs. normal controls. Our center has participated in the Diabetes Research in Children Network (DirecNet), a successful, NIH funded consortium of 5 pediatric diabetes centers and a coordinating center established to study hypoglycemia in children with T1 DM. We have excellent infrastructure, trained personnel, a highly efficient system of patient recruitment, and successful history of efficient protocol completion.