DEVELOPMENT OF HYPOGLYCEMIA IN CHILDREN WITH TYPE-1 DIABETES

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。假设：许多研究评价了1型糖尿病（T1 DM）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，旨在更仔细地定义下午运动对运动期间和第二天晚上低血糖相对风险的影响，研究对象为50名T1 DM儿童，他们正在使用强化糖尿病管理方案，包括胰岛素泵或每日多次胰岛素注射。在一个临床研究中心，采用了一种严格控制的交叉设计，包括一种监督和标准化的运动方案，以比较运动期间和下午运动后过夜与久坐一天后的低血糖发生频率。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学校结束时更活跃，此时会进行不同的运动练习和游戏。此外，运动方案的持续时间和强度被设计成模仿儿童参与此类活动的典型时间长度。 研究程序规定在运动日和久坐日使用相似的胰岛素剂量。具体而言，即使受试者通常会在运动期间或夜间降低其基础胰岛素替代，在异常强烈的体力活动日，也要在运动日遵循受试者久坐日的常规例程。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，并且具有临床相关性，因为许多使用胰岛素泵或接受早餐前剂量甘精胰岛素的青少年不会或无法调整其过夜基础胰岛素。 本研究的结果支持公认的临床观察结果，即运动有助于降低T1 DM儿童运动期间和运动后的血糖水平。我们的研究结果还支持使用灵活的糖尿病管理方案，这些方案试图在运动期间或运动后的晚上调整食物摄入和胰岛素剂量，以降低运动期间或低血糖后过夜发生低血糖的风险。在本研究中，DirecNet试图评价运动期间调整胰岛素剂量的最有效方法，以通过预防运动期间和运动后的低血糖，最大限度地提高T1 DM儿童运动的获益和安全性。 目标：本研究的主要目的是确定在运动期间中断受试者的基础速率对运动期间和运动后的葡萄糖水平的影响。 我们的目的是确定是否在运动期间停止基础率降低低血糖的发生率相比，继续基础率。 此外，我们的目的是确定与继续基础速率相比，停止基础速率时运动期间血糖的降低是否更少，与继续基础速率相比，运动期间停止基础速率是否会增加高血糖症和/或阳性酮的发生率，以及游离脂肪酸，游离胰岛素，β-羟基丁酸，和脂联素在两种研究条件下不同。 将检查持续葡萄糖探头的准确度。在我们最初的运动研究中，动态葡萄糖监测系统（CGMS）显示，与中心实验室值相比，运动期间血糖水平略偏高。可以检查家用血糖仪的准确度。HbA 1c监测仪可供家庭使用。作为辅助研究，将检查这些器械中的一种或多种的准确性。 实验设计：在本研究方案中，每例受试者有两次访视。在每次访问期间，在下午晚些时候完成结构化的锻炼协议。在其中一次访视期间（通过随机化排序），受试者将继续使用常规基础率，在另一次访视期间，将停止使用基础率。研究人群包括55例使用胰岛素泵的8. 0 - 18. 0岁T1 DM和HbA 1c 10. 0%受试者。

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.