Hypoglycemia & exercise in children with type 1 diabetes

低血糖

• 批准号: 6674785
• 负责人: PIETRO R GALASSETTI
• 金额: $ 12.56万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-25 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6674785
• 关键词: actigraphy; adolescence (12-20); blood glucose; calorimetry; clinical research; environmental adaptation; exercise; glucose clamp technique; glucose metabolism; human subject; hypoglycemia; insulin dependent diabetes mellitus; interleukin 6; middle childhood (6-11); patient oriented research

DESCRIPTION (provided by applicant): Clinical research has long been a central component in the career of the candidate. UCI's strong interest in developing metabolic research and its solid history of exercise and pediatric research, well match the candidate's research interest and offers a unique potential for career development. The candidate's long-term plan is to establish an independent line of studies focused on altered mechanisms of stress responses; gradually become an independently funded investigator; and eventually coordinate, alongside his own research, a broad -range of metabolic clinical studies by UCI investigators with a variety of research interests. Initial studies, proposed in this application, are designed to identify novel physiological mechanisms causing the alarmingly high incidence of hypoglycemia in children with Type 1 diabetes. High levels of spontaneous physical activity in these children induce rapidly changing patterns of metabolic demand, contribute to glucose instability, and often result in exercise-associated hypoglycemia. Exercise is important in diabetic children, preventing cardiovascular disease, improving glycemic control/insulin sensitivity, and exerting beneficial effects on development and growth. We hypothesize that the neuroendocrine and metabolic responses which prevent hypoglycemia during exercise in the healthy child, acutely fail in the diabetic. In adult patients, exercise responses are acutely reduced by antecedent stress; it is unknown whether this also occurs in children, who are metabolically very different from adults. In addition, based on the new observation made in the candidate's mentor's laboratory that in healthy children exercise acutely increases levels of inflammatory cytokines and growth factors, we will test the novel hypothesis that in diabetic children altered secretion of these mediators may contribute to glucose instability. IL-6, the most abundantly secreted cytokine during exercise, is most likely to impact glucose homeostasis due to recently discovered yet still unclear glucoregulatory properties. This comprehensive approach will be used to define whether adaptive responses to exercise are altered in diabetic children, as compared to controls, and if alterations correlate with gender and/or physical fitness. We will also investigate how the presence and characteristics of antecedent hypoglycemia, with emphasis on nocturnal hypoglycemia, affect children's adaptive response to exercise. Techniques will include maximal/intermittent exercise testing, euglycemic glucose clamping, indirect calorimetry, continuous glucose monitoring, stable isotope glucose and lipid turnover assessment, and hormonal, cytokine, and intermediate metabolite analysis. The results from our studies will hopefully provide the conceptual basis for new therapeutic strategies aimed at correcting the high incidence of hypoglycemia in children with diabetes.

描述（由申请人提供）： 长期以来，临床研究一直是候选人职业生涯的核心组成部分。 UCI对发展代谢研究的浓厚兴趣及其在运动和儿科研究方面的坚实历史，与候选人的研究兴趣非常匹配，并为职业发展提供了独特的潜力。 候选人的长期计划是建立一个独立的研究路线，专注于应激反应的改变机制;逐渐成为一个独立资助的研究者;并最终协调，除了他自己的研究，广泛的代谢临床研究由UCI研究人员与各种研究兴趣。 本申请中提出的初步研究旨在确定导致1型糖尿病儿童低血糖发生率惊人高的新生理机制。 这些儿童的高水平自发性体力活动会引起代谢需求模式的快速变化，导致葡萄糖不稳定，并经常导致运动相关性低血糖。 运动对糖尿病儿童很重要，可以预防心血管疾病，改善血糖控制/胰岛素敏感性，并对发育和生长产生有益影响。 我们假设，神经内分泌和代谢反应，防止低血糖在运动中的健康儿童，急性失败的糖尿病。 在成人患者中，运动反应会因先前的压力而急剧降低;尚不清楚这是否也发生在儿童中，他们的代谢与成人非常不同。 此外，根据候选人导师实验室的新观察结果，即健康儿童运动会急剧增加炎症细胞因子和生长因子的水平，我们将测试糖尿病儿童这些介质分泌的改变可能导致葡萄糖不稳定的新假设。 IL-6是运动过程中分泌最丰富的细胞因子，由于最近发现的但仍不清楚的葡萄糖调节特性，最有可能影响葡萄糖稳态。 这种全面的方法将被用来定义是否运动的适应性反应改变糖尿病儿童相比，控制，如果改变与性别和/或身体健康。 我们也将探讨先前低血糖的存在和特征，特别是夜间低血糖，如何影响儿童对运动的适应性反应。 技术将包括最大/间歇运动试验、正常血糖钳夹、间接热量测定、连续血糖监测、稳定同位素葡萄糖和脂质周转评估以及激素、细胞因子和中间代谢物分析。 我们的研究结果将有望为旨在纠正糖尿病儿童低血糖高发病率的新治疗策略提供概念基础。