Apolipoproteins and the complications of Type 1 diabetes

描述（由申请人提供）： 目的：使用DCCT/EDIC样本确定基于载脂蛋白的血浆脂蛋白亚类与1型糖尿病血管并发症（视网膜病变、肾病、颈动脉内膜增厚）的横断面和前瞻性相关性。确定对降脂和胰岛素增敏药物的反应。开发临床适用的检测方法，以预测并发症风险和治疗反应。原理：血脂异常（定量和定性）与1型糖尿病的微血管和大血管并发症有关。虽然基于载脂蛋白的脂蛋白亚类水平与非糖尿病和2型糖尿病人群的血管疾病有关，但从未在1型受试者中进行过研究，也未与并发症状态或其他脂蛋白特征相关。1型糖尿病受试者中载脂蛋白定义的亚类对潜在治疗的反应尚不清楚。假设条件：基于载脂蛋白的血浆脂蛋白亚类谱与1型糖尿病血管并发症相关，并可能决定其易感性。研究计划：第一阶段（R21）：确定100名并发症易感和100名并发症抵抗DCCT/EDIC受试者的载脂蛋白亚类谱;定义与三种并发症中每一种的相关性，选择感兴趣的亚类用于临床检测开发。第二阶段（R33）：在当地招募的1型患者中，使用阿托伐他汀、非诺贝特、Niaspan和罗格列酮进行干预，并确定效果。开发临床适用的测定。研究方法：DCCT/EDIC的储存样品已经在手，载脂蛋白亚类测定和脂蛋白-细胞相互作用研究的所有方法都在我们的实验室建立。该研究汇集了一个独特的人群（DCCT/EDIC），其脂蛋白的重要描述从未用于1型糖尿病，目的是预防和治疗并发症

DESCRIPTION (provided by applicant): Objectives: Determine cross-sectional and prospective associations of apolipoprotein-based plasma lipoprotein subclasses to vascular complications of Type 1 diabetes (retinopathy, nephropathy, carotid intimal thickening) using DCCT/EDIC samples. To define responses to lipid-lowering and insulin sensitizing drugs. To develop clinically applicable assays to predict complication risk and response to treatment. Rationale: Dyslipidemia (quantitative and qualitative) is implicated in micro- and macro-vascular complications of Type 1 diabetes. Although apolipoprotein-based lipoprotein subclass levels are implicated in vascular disease in non-diabetic and Type 2 diabetic populations, they have never been studied in Type 1 subjects, nor related to complication status or to other lipoprotein characteristics. Responses of apolipoprotein-defined subclasses to potential treatments in Type 1 diabetic subjects are unknown. Hypotheses: Apolipoprotein-based plasma lipoprotein subclass profiles are associated with, and may determine susceptibility to, vascular complications of Type 1 diabetes. Research Plan: First (R21) phase: determine apolipoprotein subclass profiles in 100 complication-prone and 100 complication-resistant DCCT/EDIC subjects; define associations with each of the three complications, select subclasses of interest for clinical assay development. Second (R33) phase: in locally-recruited Type 1 patients, intervene with atorvastatin, fenofibrate, Niaspan, and rosiglitazone and define effects. Develop clinically applicable assays. Methods: Stored samples from DCCT/EDIC are already in hand, and all methods for apolipoprotein subclass determination and for lipoprotein-cell interaction studies are established in our laboratories. The study brings together a unique population (DCCT/EDIC) with an important descriptor of lipoproteins never used in Type 1 diabetes, with the goal of preventing and treating complications