Diabetes Research Center

项目摘要/摘要 本行政副刊用于试点和可行性研究，由黄丽莎担任 首席调查员。 五分之一的青少年和年轻人患有1型糖尿病(Ayad)，表现出进食障碍 行为(DEB)--几乎是健康同龄人的两倍。多项研究表明，阿亚德 患有DEB的患者血糖控制较差，肥胖率较高，急性和 与糖尿病相关的长期并发症，包括糖尿病酮症酸中毒、微血管 并发症和死亡率。驱动DEB的机制还不是很清楚，限制了 有效的临床治疗。中枢神经系统中的下丘脑内侧基底核是一种 饲喂调控的关键区域。下丘脑胶质细胞增多症与饱腹感受损有关， 啮齿动物和人类的吞噬功能亢进和血糖失调。目前尚不清楚阿亚德是否 下丘脑胶质细胞增多症与DEB、胰岛素抵抗和/或肥胖有关，或是否有高血糖 独立驱动下丘脑胶质细胞增多症的发展，促进饮食的变化 行为和体重增加。我们建议将互补战略应用于有系统地 揭示这些复杂的相互关系。 为了评估我们的假设，即DEB是血糖控制不佳、肥胖和/或 胰岛素抵抗(所有这些都与非Ayad患者的下丘脑胶质细胞增多症有关 人群)，我们将使用一个大型的前瞻性纵向队列(在 青年)，以检验基线DEB是否能在5年的随访中预测这些结果。另外， 我们建议进行一项横断面研究，以验证来自搜索队列的发现是 适用于我们当地的Ayad诊所人群。我们的初步数据显示，阿亚德 Deb有下丘脑胶质细胞增多症的证据，但高血糖的相对贡献， 饮食行为和肥胖程度尚不清楚。我们假设阿亚德有很高的DEPS-R分数 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对下丘脑胶质细胞增多症的独立影响，我们将使用 非肥胖女性Ayad伴或不伴DEB，且有良好或 血糖控制不佳。了解血糖控制、肥胖、 临床健康结局和下丘脑胶质细胞增多症的DEB在设计中是重要的 在阿亚德的有效干预。这项提案的数据，加上我们之前的DEB调查结果， 将为未来的横断面和干预性研究(例如，GLP-1)提供科学依据 激动剂或认知行为治疗)，以确定下丘脑胶质细胞增多症在DEB中的作用。我的 未来的研究将集中在降低高血糖和/或 下丘脑胶质细胞增多症可以解决DEB并改善糖尿病相关的预后 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.