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护理标准。然而，强化治疗经常因低血糖而复杂化，低血糖随后成为维持血糖控制的限制因素。在强化治疗期间，由于胰岛素过量、葡萄糖利用过量（例如运动）或碳水化合物摄入不足，糖尿病患者会发生低血糖。幼儿和青少年有许多生活方式特征，使他们特别容易发生低血糖。此外，频繁的低血糖可能导致神经系统后遗症。利用当前的家庭葡萄糖监测能力，难以准确地定义低血糖症的真实发生率、持续时间和严重程度。连续葡萄糖监测（CGM）最近已成为一种工具，可以更仔细地检查葡萄糖模式和定义低血糖症的特征，以便制定预防低血糖症的措施。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行进一步的研究。低血糖症及其后遗症的最佳预防需要对主要血糖浓度进行近乎连续的识别和响应。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降低7-24岁1型糖尿病（T1 DM）年轻患者低血糖风险的能力。此外，我们将通过活动评估、饮食或两者同时进行来检查干预的附加变量，以确定是否可以进一步降低低血糖。在基线时，我们将在一项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（如发病年龄或糖尿病持续时间）与神经认知和神经影像学参数的发生率。我们将描述T1 DM儿童和年轻成人与正常对照组的神经解剖学差异。我们中心参与了儿童糖尿病研究网络（DirectNet），这是一个成功的、由NIH资助的联盟，由5个儿科糖尿病中心和一个协调中心组成，旨在研究T1 DM儿童的低血糖。我们拥有出色的基础设施、训练有素的人员、高效的患者招募系统以及高效完成协议的成功历史。

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.