DEVELOPMENT OF HYPOGLYCEMIA IN CHILDREN WITH TYPE-1 DIABETES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。假设：许多研究已经评估了患有1型糖尿病(T1 DM)的儿童和青少年在运动期间或运动后立即发生低血糖的发生率。DirecNet最近完成了一项研究，旨在更仔细地确定下午锻炼对运动期间和第二天晚上低血糖相对风险的影响，研究对象是50名患有T1 DM的儿童，他们正在使用胰岛素泵或每日多次注射胰岛素的强化糖尿病治疗方案。采用严格控制的交叉设计，包括监督和标准化的锻炼方案，在临床研究中心的环境中，比较锻炼期间和下午锻炼后的夜间低血糖的频率与静坐一天后的低血糖发生率。我们特别选择让受试者在下午晚些时候锻炼，因为儿童和青少年通常在放学后更活跃，那时会进行不同的体育练习和游戏。此外，运动方案的持续时间和强度被设计为模拟儿童参与此类活动的典型时间长度。研究程序规定了在锻炼和久坐当天使用类似剂量的胰岛素。具体地说，受试者在锻炼日遵循久坐一天的常规，即使受试者通常会在锻炼期间或在异常剧烈的体力活动的夜间降低他或她的基础胰岛素替代量。这种方法使我们能够检查运动本身对夜间低血糖风险的影响，这是临床上相关的，因为许多服用泵或早餐前接受甘精胰岛素的年轻人不或不能调整他们过夜的基础胰岛素。这项研究的结果支持了公认的临床观察，即运动对降低T1 DM儿童运动期间和运动后的血糖水平都有好处。我们的发现还支持使用灵活的糖尿病管理方案，试图在运动期间或运动后的晚上调整食物摄入量和胰岛素剂量，以降低运动期间或低血糖后的夜间低血糖的风险。在这项研究中，DirecNet试图评估在运动中调整胰岛素剂量的最有效方法，以通过预防运动中和运动后的低血糖来最大限度地提高运动对T1 DM儿童的益处和安全性。目的：本研究的主要目的是确定停止运动期间的基础速率对运动期间和运动后的血糖水平的影响。我们的目标是确定与继续基础速率相比，运动期间停止基础速率是否可以降低低血糖的发生率。此外，我们的目标是确定与继续基础速率相比，停止基础速率时运动中血糖的下降是否更小，与继续基础速率相比，停止运动期间的基础速率是否会增加高血糖和/或阳性酮体的发生率，以及两种研究条件下游离脂肪酸、游离胰岛素、β-羟基丁酸酯和脂联素的变化有何不同。我们将检查连续血糖传感器的准确性。在我们最初的运动研究中，连续血糖监测系统(CGMS)显示，与中心实验室值相比，运动期间有轻微的系统性偏差，倾向于更高的血糖水平。可以检查家用血糖仪的准确度。HbA1c监护仪可供家庭使用。这些设备中的一个或多个的准确性将作为辅助研究进行检查。实验设计：在本研究方案中，每个受试者进行两次访问。在每次访问期间，在下午晚些时候完成一项有组织的演习方案。在其中一次访问期间(通过随机排序)，受试者通常的基本比率将继续，而在另一次访问期间，基本比率将停止。研究人群包括55名年龄在8.0岁到18.0岁之间的T1 DM患者，使用胰岛素泵的患者中有10.0%患有糖化血红蛋白。

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. Hypothesis: A number of studies have evaluated the incidence of hypoglycemia during or immediately following exercise in children and adolescents with Type-1 Diabetes Mellitus (T1DM). DirecNet recently completed a study that was designed to more carefully define the effect of afternoon exercise on the relative risk of hypoglycemia during exercise and during the following night in a cohort of 50 children with T1DM who were using an intensive diabetes management regimen involving either insulin pumps or multiple daily insulin injections. A carefully-controlled, cross-over design that involved a supervised and standardized exercise protocol was utilized to compare the frequency of hypoglycemia during exercise and overnight following afternoon exercise with that following a sedentary day in a clinical research center setting. We specifically chose to have the subjects exercise in the late afternoon as children and adolescents often are more active at the end of the school day, when different athletic practice and game sessions take place. In addition, the duration and intensity of the exercise regimen was designed to mimic a typical length of time children are involved in such activities. The study procedures specified the use of similar insulin doses on both the exercise and sedentary day. Specifically, the subject's usual routine for a sedentary day was followed on the exercise day even if the subject typically would have lowered his or her basal insulin replacement during exercise or overnight, on days of unusually intense physical activity. This approach allowed us to examine the effect of exercise per se on the risk of nocturnal hypoglycemia and it is clinically relevant, since many youngsters on pumps or who receive pre-breakfast doses of glargine insulin do not or cannot adjust their overnight basal insulin. The findings of this study supported the well-recognized clinical observation that exercise has benefit in lowering plasma glucose levels both during and following exercise in children with T1DM. Our findings also supported the use of flexible diabetes management regimens that attempt to adjust food intake and insulin dosing during or on evenings following exercise to reduce the risk of hypoglycemia during exercise or overnight following hypoglycemia. In the present study, DirecNet attempts to evaluate the most effective methods of adjusting insulin doses during exercise in order to maximize the benefits and safety of exercise in children with T1DM by preventing hypoglycemia during and following exercise. Goals: The primary objective of the study is to determine the effects of discontinuing a subject's basal rate during exercise on the glucose level during and following exercise. We aim to determine whether discontinuing the basal rate during exercise reduces the incidence of hypoglycemia compared with continuing the basal rate. Additionally, we aim to determine whether the decrease in blood glucose during exercise is less when the basal rate is discontinued compared with when the basal rate is continued, whether discontinuing the basal rate during exercise increases the incidence of hyperglycemia and/or positive ketones compared with continuing the basal rate, and how changes in free fatty acids, free insulin, beta-hydroxybuterate, and adiponectin differ under the two study conditions. The accuracy of a continuous glucose sensor will be examined. In our initial exercise study, the Continuous Glucose Monitoring System (CGMS) showed a slight systematic bias during exercise towards higher blood glucose levels compared with the central lab values. The accuracy of a home glucose meter may be examined. HbA1c monitors are available for home use. The accuracy of one or more of these devices will be examined as an ancillary study. Experimental Design: In this study protocol, each subject has two visits. During each visit, a structured exercise protocol is completed in the late afternoon. During one of the visits (ordered through randomization), the subject's usual basal rate will be continued and during the other visit, the basal rate will be discontinued. The study population includes 55 subjects between 8.0 and 18.0 yrs old with T1DM and HbA1c 10.0% using an insulin pump.