Diabetes Research Center

糖尿病研究中心

• 批准号: 10425125
• 负责人: Steven Emanuel Kahn
• 金额: $ 8.9万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425125
• 关键词: Acute; Address; Administrative Supplement; Adolescent and Young Adult; Adult; Agonist; Area; Brain; Clinic; Clinical; Clinical Treatment; Cognitive Therapy; Complex; Complications of Diabetes Mellitus; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Diabetic Ketoacidosis; Eating Behavior; Eating Disorders; Exhibits; Feasibility Studies; Female; Future; Gliosis; Glucose; Health; Human; Hyperglycemia; Hyperphagia; Hypothalamic structure; Impairment; Insulin Resistance; Insulin-Dependent Diabetes Mellitus; Intervention; Intervention Studies; Link; Longitudinal cohort; Magnetic Resonance Imaging; Microvascular Dysfunction; Morbidity - disease rate; Neuraxis; Non obese; Obesity; Outcome; Pilot Projects; Population; Principal Investigator; Regulation; Research; Risk Factors; Rodent; Role; SEARCH for Diabetes in Youth; Satiation; Structure; Testing; Vulnerable Populations; Weight Gain; cohort; design; effective intervention; feeding; follow-up; glucagon-like peptide 1; glycemic control; high risk; improved; mortality; obesity risk; outcome prediction; patient population; peer; prospective

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.

项目摘要/摘要 这种行政补充是针对Alyssa Huang的试点和可行性研究的 首席研究员。 五分之一的青少年和患有1型糖尿病（AYAD）的年轻人暴露了无序的饮食 行为（DEB） - 几乎是健康同龄人的率的两倍。几项研究表明Ayad DEB具有较差的血糖控制，较高的肥胖率以及更高的急性风险 长期糖尿病相关并发症，包括糖尿病性酮症酸中毒，微血管 并发症和死亡率。驱动DEB的机制尚不清楚，限制了 有效的临床治疗。中枢神经系统中的中丘脑下丘脑是 进食调节的关键领域。下丘脑神经病与饱腹感相关， 啮齿动物和人类中的心脏和葡萄糖失调。尚不清楚是否是 具有与DEB，胰岛素抵抗和/或肥胖有关的下丘脑神经胶质病，或者是否高血糖 独立驱动下丘脑神经病的发展，促进饮食变化 行为和体重增加。我们建议将完整的策略应用于系统 揭示这些复杂的相互关系。 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（所有与非雅德的下丘脑神经胶质病有关 人群），我们将使用一个大型的前瞻性纵向队列（寻找糖尿病 青年）测试基线DEB是否在5年随访中预测这些结果。此外， 我们提出了一项横断面研究，以验证搜索队列的发现是 适用于我们当地的Ayad诊所人口。我们的初步数据表明Ayad与 DEB有下丘脑神经病的证据，但是高血糖的相对贡献， 饮食行为和肥胖尚不清楚。我们假设AYAD具有较高的DEPS-R分数 不良血糖控制的下丘脑神经胶质病程度更高，与肥胖无关。 为了评估血糖控制和DEB对下丘脑神经病的独立影响，我们将使用 非肥胖的Ayad女性的非侵入性结构MRI，有或没有DEB，并且有良好或 血糖控制不良。了解血糖控制，肥胖的相对关联， 具有临床健康结果和下丘脑神经胶质病的DEB在设计中很重要 在Ayad的有效干预措施。该提案的数据以及我们先前的DEB调查结果， 将为未来的横断面和干预研究提供科学原理（例如，GLP-1 激动剂或认知行为治疗）定义下丘脑神经胶质病在DEB中的作用。我的 未来的研究将重点介绍减少高血糖和/或 下丘脑神经病可以解决DEB并改善与糖尿病有关的结果 脆弱的人口。