Seasonal and Viral Determinants of Type 1 Diabetes Onset, Remission, and Glycemic Control

1 型糖尿病发病、缓解和血糖控制的季节性和病毒决定因素

基本信息

批准号：
9908075
负责人：
Christina M. Astley
金额：
$ 19.45万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908075
关键词：
Acute Antibodies Autoimmunity Automobile Driving Beta Cell Bioinformatics Biology Boston Calendar Caring Cell physiology Child Child Guidance Childhood Chronic Data Data Set Databases Detection Deterioration Diabetes prevention Diagnosis Disease Disease remission Dose Education Endocrinologist Endocrinology Environment Environmental Exposure Environmental Risk Factor Epidemic Epidemiologic Methods Epidemiologist Epidemiology Etiology Event Functional disorder Future Genetic Glucose Glycosylated Hemoglobin Glycosylated hemoglobin A Goals Health Holidays Human Hyperglycemia Hypoglycemia Immune Incidence Individual Infection Infectious Disease Epidemiology Inflammation Informatics Insulin Insulin-Dependent Diabetes Mellitus Intervention Investigation Measures Mentored Patient-Oriented Research Career Development Award Mentorship Metabolic stress Methodology Methods Modeling Newly Diagnosed Onset of illness Outcome Pathogenesis Pattern Pediatric Hospitals Peptide antibodies Phenotype Physicians Play Population Prevention Prevention strategy Prospective cohort Research Research Personnel Residual state Resolution Risk Role Sampling Schools Scientist Seasons Series Sports Statistical Methods Statistical Models System Technology Testing Time Time Series Analysis Time trend Training Variant Viral Viral Antibodies Virus Virus Diseases Weather base clinical care clinically relevant cohort complex data density diabetes management diabetes pathogenesis epidemiology study evidence base experience glucose monitor glycemic control improved infectious disease model innovation insulin dependent diabetes mellitus onset novel outcome prediction prevent programs skills social supportive environment syndromic surveillance tool trend

项目摘要

PROJECT SUMMARY/ABSTRACT Glycemic control strongly predicts outcomes in type 1 diabetes (T1D), yet many children with T1D fail to achieve glycemic targets. This problem is magnified by rising T1D incidence and incomplete understanding of the etiology of T1D. Winter predominance of T1D onset, worsening of glycemic control, and loss of residual beta cell function suggest that there may be shared seasonal triggers that contribute to T1D pathogenesis. Epidemiologic studies using 3-month average glycemic control measures (i.e. glycated hemoglobin) obscure temporal trends. Investigators of potential viral triggers have examined the role of prespecified viruses, but have not conducted comprehensive testing for all human viruses. Wide use of continuous glucose monitoring (CGM) and the availability of systematic tests for all prior viral exposures can now be leveraged to dissect the causes of T1D and highlight relevant biology for T1D prevention and management. Dr. Christina Mills Astley, a pediatric endocrinologist and epidemiologist, will approach seasonality of incident and prevalent T1D using an innovative combination of translational phenotyping, time-series analyses, and integration of external datasets in her Mentored Patient-Oriented Research Career Development Award. She now seeks to build on her prior research experiences in infectious diseases modeling and causal inference for complex data, while acquiring new skills in time-series analysis and bioinformatics, and developing expertise in T1D pathophysiology, including the role of immune dysregulation, inflammation, and metabolic stress. Combined with the high-quality mentorship and supportive environment at Boston Children’s Hospital, these tools will broaden her expertise and enable her to establish an independent research program. In Aim 1, Dr. Astley will use pediatric T1D CGM data and time-series methods (e.g. change point, autoregression, temporal clustering) to define seasonal patterns, both acute and chronic, in clinically-relevant CGM-based glycemic control measures (e.g. coefficient of variation, time in range). In Aim 2, she will quantify the effect of individual, social, and environmental exposures on these glycemic control measures. Finally, in Aim 3, Dr. Astley will apply comprehensive antibody profiling (VirScan) to test which viral infection(s) drive T1D onset, end of remission, and seasonal dysglycemia. Together the results of these investigations will form the basis of a data-driven approach to understand seasonality in T1D, which in turn may be used to recognize optimal timing for anticipatory guidance to mitigate the risk of seasonal hyperglycemia and hypoglycemia, and to identify potential targets for intervention to slow the progression of T1D. Dr. Astley seeks to become an independent physician-scientist with unique expertise in computational epidemiology, translational methodologies, and T1D pathogenesis, so as to improve prevention and treatment. This K23 award will afford her the mentorship, training, expertise, and research to achieve these goals.

项目概要/摘要血糖控制强烈预测 1 型糖尿病 (T1D) 的结果，但许多患有 T1D 的儿童未能由于 T1D 发病率上升和对血糖的了解不完全，这一问题变得更加严重。 T1D 的病因学是 T1D 的冬季发病、血糖控制恶化和残余血糖丧失。 β 细胞功能表明可能存在共同的季节性触发因素导致 T1D 发病机制。使用 3 个月平均血糖控制措施（即糖化血红蛋白）进行的流行病学研究模糊潜在病毒触发因素的研究人员已经研究了预先指定的病毒的作用，但是尚未对所有人类病毒进行全面检测。连续血糖监测的广泛使用。（CGM）和对所有先前病毒暴露的系统测试的可用性现在可以用来剖析 T1D 的病因并强调 T1D 预防和管理的相关生物学。儿科内分泌学家和流行病学家 Christina Mills Astley 博士将研究事件的季节性和流行的 T1D，使用转化表型分析、时间序列分析和她将外部数据集整合到她的以患者为导向的研究职业发展奖中。现在寻求以她之前在传染病建模和因果推断方面的研究经验为基础复杂的数据，同时获得时间序列分析和生物信息学的新技能，并发展以下方面的专业知识 T1D 病理生理学，包括免疫失调、炎症和代谢应激的作用。结合波士顿儿童医院的高质量指导和支持环境，这些工具将扩大她的专业知识，并使她能够建立一个独立的研究项目。在目标 1 中，Astley 博士将使用儿科 T1D CGM 数据和时间序列方法（例如变化点、自回归、时间聚类）来定义临床相关的季节性模式，包括急性和慢性基于 CGM 的血糖控制措施（例如变异系数、范围内的时间），她将量化目标 2。最后，个人、社会和环境暴露对这些血糖控制措施的影响。目标 3，Astley 博士将应用全面的抗体分析 (VirScan) 来测试哪些病毒感染会导致 T1D 这些调查的结果将共同形成发病、缓解结束和季节性血糖异常。以数据驱动方法为基础来了解 T1D 的季节性，进而可用于识别降低季节性高血糖和低血糖风险的预期指导的最佳时机，以及确定减缓 T1D 进展的潜在干预目标。 Astley 博士致力于成为一名独立的医师科学家，在计算方面拥有独特的专业知识流行病学、转化方法学和 T1D 发病机制，以改善预防和治疗。 K23 奖项将为她提供指导、培训、专业知识和研究来实现这些目标。