A Novel Approach Applying CGM Metrics to Identify a Prediabetic State

一种应用 CGM 指标来识别糖尿病前期状态的新方法

• 批准号: 8642867
• 负责人: MASSIMO T PIETROPAOLO
• 金额: $ 14.26万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8642867
• 关键词: Algorithms; Autoantibodies; Biological Markers; Blood Glucose; CD3 Antigens; Categories; Cells; Clinical; Clinical Trials; Communities; Data; Development; Diabetes Mellitus; Diagnosis; Enrollment; Evaluation; Event; Exhibits; Fasting; First Degree Relative; Future; Genotype; Glucose; Glycemic Index; Immunologics; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention Trial; Investigation; Letters; Life; Metabolic; Methods; Metric; Michigan; Monitor; Natural History; Normal Range; OGTT; Oral; Paper; Participant; Pathogenesis; Pathway interactions; Patients; Phase; Phenotype; Pilot Projects; Play; Population; Practice Guidelines; Prediabetes syndrome; Prevention; Relative (related person); Reporting; Research Personnel; Risk; Risk Factors; Role; Sample Size; Stress; Testing; Universities; Variant; base; biobank; diabetic patient; follow-up; glucose monitor; graphical user interface; high risk; improved; interstitial; islet; islet cell antibody; mathematical model; multi-scale modeling; novel strategies; pre-clinical; prevent; proband; public health relevance; response; tool; type I diabetic

DESCRIPTION (provided by applicant): The proposed investigation will examine indexes of glycemic variability using advanced Continuous Glucose Monitoring (CGM) metrics in first degree relatives of Type 1 diabetic (T1D) probands to capture new information relevant to T1D pathogenesis and prediction. We propose to utilize participants who are currently enrolled in the TrialNet Natural History Study (Living Biobank). These subjects are longitudinally followed and deeply phenotyped with respect to multiple islet-related autoantibodies, HLA genotyping, metabolic assessment and many other risk factors. To the best of our knowledge, an integrated approach providing a complete and accurate assessment of glycemic excursions during the preclinical state of T1D has not been applied in TrialNet participants prior to the development and diagnosis of full-blown T1D. We believe the use of a combination of CGM-based metrics to assess indexes of glycemic variability will assist the identification of first-degree relatives likly to progress to the clinical onset of T1D. We hypothesize that first-degree relatives of T1D patients with ongoing immunological abnormalities (presence of 2 or e3 islet autoantibodies: insulin, GAD65, IA-2 and islet cell antibodies [ICA]) exhibit wide interstitial glucose variations detected by CGM as compared to subjects with the presence of 1 islet autoantibody. Such excursions may also occur in relatives with immunologic abnormalities, normal fasting glycemic values and normal Oral Glucose Tolerance Test (OGTT) and would otherwise go undetected. We have recently reported the development of the Continuous Glucose Monitoring - Graphical User Interface for Diabetes Evaluation (CGM-GUIDE) that provides a superior assessment of a patient's blood glucose excursions. We have assembled an unprecedented team of leading experts in: 1. Formulating practice guidelines for determining settings where patients are most likely to benefit from the use of CGM; 2. The field of mathematical modeling and CGM metrics development; and 3. Expertise in metabolic abnormalities and TrialNet-supported clinical trials for T1D. The proposed study should ultimately be useful as a new tool in combination with other immunologic as well as mechanistic biomarkers to improve prediction, understand the pathogenesis and ultimately to more accurately evaluate the response to treatment in future intervention trials aimed at preventing type 1 diabetes.

描述（由申请人提供）：拟议的调查将使用先进的连续葡萄糖监测（CGM）指标检查血糖变异性指数，该指标是1型糖尿病（T1D）概率的一级亲属，以捕获与T1D病原体和预测有关的新信息。我们建议利用目前正在参加试验网自然历史研究（Living Biobank）的参与者。这些受试者在多个胰岛相关的自身抗体，HLA基因分型，代谢评估和许多其他风险因素方面进行了纵向遵循并深入表型。据我们所知，在T1D的临床前状态期间，尚未在试验网络参与者中使用完整，准确评估血糖偏移的综合方法。我们认为，将基于CGM的指标组合使用来评估血糖变异性指数将有助于鉴定一级亲戚喜欢发展到T1D的临床发作。我们假设具有持续免疫学异常的T1D患者的一级亲戚（存在2或E3胰岛自身抗体：胰岛素，GAD65，IA-2和ISLET细胞抗体[ICA]）表现出与cgm相比，与受试者相比，CGM检测到的宽阔的间质葡萄糖变化表现出了较广泛的葡萄糖。这种偏移也可能发生在具有免疫异常，正常禁食血糖价值和正常口服葡萄糖耐量测试（OGTT）的亲戚中，否则未被发现。我们最近报道了连续葡萄糖监测的发展 - 用于糖尿病评估（CGM指定）的图形用户界面，该界面可对患者的血糖散发进行卓越的评估。我们已经组建了一个前所未有的领先专家团队：1。制定实践指南，以确定患者最有可能从使用CGM中受益的设置； 2。数学建模和CGM指标开发领域；和3。代谢异常和试验网络支持的T1D临床试验的专业知识。拟议的研究最终应作为与其他免疫学和机械生物标志物相结合的新工具，以改善预测，了解发病机理，并最终更准确地评估旨在防止1型糖尿病的未来干预试验中对治疗的反应。