Biomarkers of Vascular Disease Progression in Type 1 Diabetes Mellitus

1 型糖尿病血管疾病进展的生物标志物

• 批准号: 8119775
• 负责人: MARIA F LOPES-VIRELLA
• 金额: $ 39.51万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8119775
• 关键词: Algorithms; Alteplase; Biological Assay; Biological Markers; Blood Vessels; Coagulation Process; Complication; Complications of Diabetes Mellitus; Development; Diabetes Mellitus; Disease Progression; E-Selectin; Endothelial Cells; Enrollment; Fibrinogen; Functional disorder; Glycosylated hemoglobin A; Goals; Hypertension; Inflammation; Insulin-Dependent Diabetes Mellitus; Intercellular adhesion molecule 1; Interleukin-6; Lipids; Measurement; Measures; Metabolic; Patients; Phase; Plasma; Plasminogen Activator Inhibitor 1; Predictive Value; Research; Research Personnel; Risk; Risk Factors; Sampling; Secondary to; Smoking; System; TNF gene; TNFR-Fc fusion protein; Vascular Cell Adhesion Molecule-1; Vascular Diseases; arm; cohort; follow-up; glycemic control; high risk; imprint; macrovascular disease; novel; receptor

DESCRIPTION (provided by applicant): The goal of the proposed research is to elucidate the value of selected biomarkers in predicting the development of micro- and macro-vascular complications in Type 1 diabetes and to determine if several risk factors, some unique to diabetes, may interact to augment vascular risk. We will measure three classes of biomarkers: i.) endothelial cell dysfunction - soluble ICAM-1, VCAM, and E selectin; ii.) inflammation-interleukin-6, CRP, and soluble TNF ?receptors; iii.) fibrinolytic and clotting system - fibrinogen, plasminogen activator inhibitor-1 and tissue plasminogen activator. We will assay these biomarkers longitudinally in samples, obtained from the well characterized DCCT/EDIC cohort of type 1 diabetes, at the DCCT baseline and closeout phases, and in years 3-5 and 9-12 of the EDIC phase of the study. We hypothesize that the pathogenic interaction between inflammation and endothelial cell/clotting/fibrinolytic dysfunction greatly contributes to the accelerated development of vascular complications in diabetes, and that selective clustering of the above biomarkers will predict patients at high risk to develop complications. Furthermore, we also hypothesize that the persistent, lower rate of complications observed in patients enrolled in the intensive glycemic control arm of the DCCT study even 10 years after the close-out of the DCCT is secondary to the effect of sustained glycemic control in one or more of the biomarkers we propose to measure. We will evaluate this hypothesis in three aims. Aim 1 will determine if concentrations of any biomarker or cluster of biomarkers, will predict the development of micro- or macro-vascular complications in this cohort and whether they predict a select group of complications, all vascular complications, or a single complication. Aim 2 will assess if levels of any of the biomarkers studied that remain similar, during the EDIC phase of the study, to those measured at DCCT close-out can explain the slower progression of complications observed in patients enrolled in the intensive glycemic control arm of the DCCT/EDIC study over the next decade of follow-up and, therefore, explain the "metabolic imprint" phenomenon postulated by the DCCT/EDIC group of investigators. Aim 3 will assess the value of the panel of novel biomarkers identified in Aim 1 to predict diabetic complications by assaying these biomarkers in samples collected at entry into the DCCT trial from patients not used to construct the biomarker risk algorithm.

描述（由申请人提供）：拟议的研究的目的是阐明所选生物标志物在预测1型糖尿病中微血管并发症发展的价值，并确定一些糖尿病的危险因素是否可以与增强血管风险相互作用。我们将测量三类生物标志物：i。）内皮细胞功能障碍 - 可溶性ICAM -1，VCAM和E SELECTIN； ii。）炎症 - 插入素6，CRP和可溶性TNF？受体； iii。）纤维蛋白水解和凝血系统 - 纤维蛋白原，纤溶酶原激活剂1和组织纤溶酶原激活剂。我们将在样品中纵向测定这些生物标志物，这些样品是从DCCT/1型糖尿病的DCCT/EDIC队列中获得的，在DCCT基线和关闭阶段，以及该研究的EDIC阶段的3-5和9-12年。我们假设炎症与内皮细胞/凝结/纤维蛋白水解功能障碍之间的致病相互作用极大地有助于加速糖尿病的血管并发症的发展，并且上述生物标志物的选择性聚类将预测患者高风险发育并发症的患者。此外，我们还假设，即使在DCCT结束后的10年，DCCT研究的强化血糖控制臂的患者中观察到的持续性，较低的并发症率是持续性血糖控制的效果，即我们提出的一个或多个生物标志物的持续性血糖控制作用。我们将以三个目标评估这一假设。 AIM 1将确定生物标志物的任何生物标志物或簇的浓度是否会预测该队列中微血管并发症的发展，以及它们是否预测了一组并发症，所有血管并发症或单一并发症。 Aim 2 will assess if levels of any of the biomarkers studied that remain similar, during the EDIC phase of the study, to those measured at DCCT close-out can explain the slower progression of complications observed in patients enrolled in the intensive glycemic control arm of the DCCT/EDIC study over the next decade of follow-up and, therefore, explain the "metabolic imprint" phenomenon postulated by the DCCT/EDIC group of investigators. AIM 3将评估AIM 1中鉴定出的新生物标志物小组的价值，以预测糖尿病并发症，通过在进入DCCT试验中收集的样品中的这些生物标志物，这些生物标志物是从未用于构建生物标志物风险算法的患者中。

项目成果

Response to comment on Lopes-Virella et al. Baseline markers of inflammation are associated with progression to macroalbuminuria in type 1 diabetic subjects. Diabetes care 2013;36:2317-2323.

对 Lopes-Virella 等人的评论的回应

• DOI: 10.2337/dc13-2976
• 发表时间: 2014
• 期刊: Diabetes care
• 影响因子: 16.2
• 作者: Lopes-Virella,MariaF;Baker,NathanielL;Hunt,KellyJ;Cleary,PatriciaA;Klein,Richard;Virella,Gabriel;DCCT/EDICResearchGroup
• 通讯作者: DCCT/EDICResearchGroup

Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.

• DOI: 10.3390/ijms241814015
• 发表时间: 2023-09-13
• 期刊: International journal of molecular sciences
• 影响因子: 5.6