Diabetes Research Center

项目概要/摘要 本行政补充文件是一项试点和可行性研究，由Alyssa Huang担任 首席研究员。 五分之一的1型糖尿病（AYAD）青少年和年轻人表现出饮食失调 行为（DEB）-几乎是健康同龄人的两倍。多项研究表明， DEB患者的血糖控制较差，肥胖率较高，急性和 长期糖尿病相关并发症，包括糖尿病酮症酸中毒、微血管 并发症和死亡率。驱动DEB的机制尚未得到很好的理解， 有效的临床治疗。中枢神经系统中的下丘脑中底核是一个 饲养管理的关键领域。下丘脑神经胶质增生与饱食感受损有关， 摄食过多和血糖失调。目前尚不清楚AYAD是否 患有与DEB、胰岛素抵抗和/或肥胖相关的下丘脑神经胶质增生，或者如果高血糖 独立驱动下丘脑神经胶质增生的发展，促进饮食的变化， 行为和体重增加。我们建议采用补充战略， 揭示这些复杂的相互关系。 为了评估我们的假设，即DEB是血糖控制不良、肥胖和/或 胰岛素抵抗（所有这些都与非AYAD患者的下丘脑神经胶质增生有关） 人群），我们将使用一个大型的前瞻性纵向队列（2010年糖尿病研究）。 青年），以测试基线DEB是否预测5年随访时的这些结果。此外，本发明还 我们提出了一项横断面研究，以验证来自研究队列的发现是 适用于我们当地的AYAD诊所人群。我们的初步数据表明， DEB有下丘脑神经胶质增生的证据，但高血糖的相对贡献， 饮食行为和肥胖还不清楚。我们假设AYAD具有高DEPS-R评分 血糖控制差的患者下丘脑胶质细胞增生程度更高，与肥胖无关。 为了评估血糖控制和DEB对下丘脑神经胶质增生的独立影响，我们将使用 非肥胖AYAD女性（有或无DEB）的非侵入性结构MRI， 血糖控制不佳。了解血糖控制，肥胖， 和DEB与临床健康结果和下丘脑神经胶质增生在设计中很重要 有效的干预措施。该提案的数据，以及我们之前的DEB调查结果， 将为未来的横断面和干预研究提供科学依据（例如，GLP-1 激动剂或认知行为治疗），以确定下丘脑神经胶质增生在DEB中的作用。 未来的研究将集中在是否干预，减少高血糖症和/或 下丘脑神经胶质增生可以解决DEB和改善糖尿病相关的结果， 弱势群体。

PROJECT SUMMARY/ABSTRACT This administrative supplement is for a pilot and feasibility study with Alyssa Huang as the Principal Investigator. One in five adolescents and young adults with type 1 diabetes (AYAD) exhibit disordered eating behaviors (DEB)—nearly twice the rate among healthy peers. Several studies show that AYAD with DEB have worse glycemic control, higher rates of obesity, and higher risk of acute and long-term diabetes related complications including diabetic ketoacidosis, microvascular complications, and mortality. The mechanisms that drive DEB are not well understood, limiting effective clinical treatment. The mediobasal hypothalamus in the central nervous system is a key area of feeding regulation. Hypothalamic gliosis is associated with impaired satiety, hyperphagia, and glucose dysregulation in rodents and humans. It is unknown whether AYAD have hypothalamic gliosis related to DEB, insulin resistance, and/or obesity, or if hyperglycemia independently drives the development of hypothalamic gliosis, promoting changes in eating behavior and weight gain. We propose to apply complementary strategies to systematically uncover these complex interrelationships. To assess our hypothesis that DEB is a risk factor for poor glycemic control, adiposity, and/or insulin resistance (all of which have been associated with hypothalamic gliosis in non-AYAD populations), we will use a large, prospective longitudinal cohort (SEARCH for Diabetes in Youth) to test whether baseline DEB predicts these outcomes at 5-year follow-up. Additionally, we propose a cross-sectional study to validate that findings from the SEARCH cohort are applicable to our local AYAD clinic population. Our preliminary data suggest that AYAD with DEB have evidence of hypothalamic gliosis, but the relative contributions of hyperglycemia, eating behavior, and adiposity are unclear. We hypothesize AYAD with high DEPS-R scores and poor glycemic control have higher degree of hypothalamic gliosis, independent of adiposity. To assess independent effects of glycemic control and DEB on hypothalamic gliosis, we will use non-invasive structural MRI on non-obese AYAD females with or without DEB, and with good or poor glycemic control. Understanding the relative associations of glycemic control, adiposity, and DEB with clinical health outcomes and with hypothalamic gliosis is important in designing effective interventions in AYAD. Data from this proposal, together with our prior DEB findings, will provide scientific rationale for future cross-sectional and intervention studies (e.g., GLP-1 agonists or cognitive behavioral treatment) to define the role of hypothalamic gliosis in DEB. My future research will focus on whether interventions that reduce hyperglycemia and/or hypothalamic gliosis can address DEB and improve diabetes-related outcomes in this vulnerable population.