Assay for Monitoring Glycemic Control in Diabetics

监测糖尿病患者血糖控制的测定

• 批准号: 7807595
• 负责人: Ralph Ballerstadt
• 金额: $ 25.75万
• 依托单位: BIOTEX, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807595
• 关键词: Affect; Albumins; Antibodies; Artificial beta Cells; Binding; Binding Sites; Biological Assay; Blood; Blood specimen; Calibration; Cause of Death; Classification; Clinical; Clinical effectiveness; DNA; Detection; Diabetes Mellitus; Diagnostic; Diet; Disadvantaged; Disease; Elements; Evaluation; Evolution; Feedback; Fibrinogen; Fluorescence; Fluorescent Dyes; Fructosamine; Future; Glucose; Glycosylated Hemoglobin; Glycosylated hemoglobin A; Goals; Half-Life; Hemoglobin; Hemoglobinopathies; Hemolysis; Home environment; Human; Immobilization; Immunoglobulin G; Immunoglobulin M; In Vitro; Indium; Individual; Injection of therapeutic agent; Insulin; Insulin Infusion Systems; Insulin-Dependent Diabetes Mellitus; Iron deficiency anemia; Judgment; Left; Libraries; Life; Life Style; Ligands; Magnetism; Measures; Methods; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Oligonucleotides; Patients; Phase; Physical condensation; Pregnancy; Property; Proteins; Protocols documentation; Pump; Quantum Dots; Reaction; Reader; Recording of previous events; Relative (related person); Reproducibility; Research Personnel; Risk Factors; Sampling; Sensitivity and Specificity; Serum; Serum Albumin; Serum Proteins; Signal Transduction; Solid; Specificity; Structure; Surface Plasmon Resonance; System; Technology; Testing; Time; United States; Woman; amino group; aptamer; base; clinically relevant; comparative; cost; diabetes management; diabetes mellitus therapy; diabetic; glycation; glycemic control; high risk; improved; innovation; magnetic beads; novel strategies; particle; public health relevance; research study; synthetic construct; tool; trend; type I and type II diabetes

DESCRIPTION (provided by applicant): Diabetes is currently believed to afflict over 100 million people worldwide and nearly 18 million in the United States. In the U.S. this disorder, along with its associated complications, is ranked as the seventh leading cause of death. To significantly improve diabetes management, there is an urgent need for diagnostics to assess compliance to of diabetics to various treatment methods, and, in particular, to intensive insulin therapy (e.g. by insulin injection, pump use, or by the implementation of a closed loop system in the near future). BioTex researchers propose to develop an affordable diagnostic kit for retrospective assessment of glycemic control in diabetics over a preceding time frame of 1-6 weeks. BioTex' innovative assay will simultaneously targets several glycation products in serum, whose degree in non-enzymatic condensation reaction with glucose correlates with the mean glucose level in blood. Since the glycated protein targets will have different life times, the assay will provide the mean glucose level not only for one time frame, but 5 different time frames within the past 6 weeks. The innovative element of the the disposable diagnostic kit will be the use aptamers - short oligonucleotides - for specific binding to the protein targets, and quantum dots for fluorescence detection. To accomplish this task, in Phase I we will perform proof-of- concept by selecting aptamers specific to five glycated proteins (e.g. hemoglobin HbA1c, IgM, IgG, serum albumin, and fibrinogen), followed by fluorescence detection using a microplate reader. Aptamers will be selected from random libraries by SELEX protocol (Systematic Evolution of Ligands by Exponential enrichment) that will allow us to screen ligands to a selected number of prominent glycated proteins (in an automated and rational way within a few days only). In stark contrast to antibodies, aptamers are much more affordable to produce with much better reproducibility. BioTex researchers are confident that this novel approach, if successful, can significantly enhance the clinical relevance of retrospective monitoring of glycemic control, especially for assessing clinical effectiveness of a closed loop system. PUBLIC HEALTH RELEVANCE: There is an urgent need for diagnostics to assess compliance to various treatment methods of diabetes, and, in particular, intensive insulin therapy (e.g. by using insulin pumps, or an artificial beta cell in the near future). Diabetes is currently believed to afflict over 100 million people worldwide and nearly 18 million in the United States. In the U.S. this disorder, along with its associated complications, is ranked as the seventh leading cause of death. BioTex proposes to develop a innovative diagnostic kit for assessing compliance of diabetics, who undergo intensive insulin therapy. Compliance will be assessed by retrospective evaluation of glycemic control (mean glucose level) over the preceding 6-8 weeks (1-6 weeks) within different time windows. The clinical utility of this kit will allow the clinician to make more meaningful decisions about adjustments of insulin therapy, life-style, or diet.

描述(申请人提供)：糖尿病目前被认为困扰着全球1亿多人和美国近1800万人。在美国，这种疾病及其相关并发症被列为第七大死亡原因。为了显著改善糖尿病管理，迫切需要诊断学评估糖尿病患者对各种治疗方法的依从性，特别是强化胰岛素治疗(例如，通过胰岛素注射、泵使用或在不久的将来实施闭环系统)。BioTex的研究人员建议开发一种负担得起的诊断试剂盒，用于回顾评估糖尿病患者1-6周前的血糖控制情况。BioTex的创新测试将同时针对血清中的几种糖基化产物，其与葡萄糖的非酶缩合反应程度与血液中的平均葡萄糖水平相关。由于糖化蛋白靶标的寿命不同，该检测将不仅提供一个时间段的平均血糖水平，而且提供过去6周内的5个不同时间段的平均血糖水平。一次性诊断试剂盒的创新元素将是使用适配子-短寡核苷酸-用于与蛋白质靶标的特定结合，以及用于荧光检测的量子点。为了完成这项任务，在第一阶段，我们将通过选择五种糖化蛋白(例如，血红蛋白HbA1c、IgM、Ig G、血清白蛋白和纤维蛋白原)的特异性适配子来执行概念验证，然后使用微型平板阅读器进行荧光检测。我们将通过SELEX协议(指数富集法的配体系统进化)从随机文库中选择适配子，这将允许我们筛选选定数量的显著糖化蛋白的配体(仅在几天内以自动化和理性的方式)。与抗体形成鲜明对比的是，适配子的生产成本更低，重复性也更好。BioTex的研究人员相信，如果成功，这种新的方法可以显著提高血糖控制回溯性监测的临床相关性，特别是在评估闭环系统的临床有效性方面。 公共卫生相关性：迫切需要诊断学评估糖尿病各种治疗方法的依从性，特别是强化胰岛素治疗(例如，使用胰岛素泵，或在不久的将来使用人造β细胞)。据信，目前全世界有超过1亿人患有糖尿病，美国有近1800万人患有糖尿病。在美国，这种疾病及其相关并发症被列为第七大死亡原因。BioTex建议开发一种创新的诊断试剂盒，用于评估接受强化胰岛素治疗的糖尿病患者的依从性。依从性将通过在不同的时间窗口内对之前6-8周(1-6周)的血糖控制(平均血糖水平)进行回顾性评估来评估。这一试剂盒的临床实用性将使临床医生能够就胰岛素治疗、生活方式或饮食的调整做出更有意义的决定。