? 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 ? ?
| Jenkins, Alicia J; Fu, Dongxu; Azar, Madona et al. (2014) Clinical correlates of serum pigment epithelium-derived factor in type 2 diabetes patients. J Diabetes Complications 28:353-9 |
| Yu, Jeremy Y; Lyons, Timothy J (2013) Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina. J Clin Exp Ophthalmol 4: |
| Dong, Yunzhou; Wu, Yong; Wu, Mingyuan et al. (2009) Activation of protease calpain by oxidized and glycated LDL increases the degradation of endothelial nitric oxide synthase. J Cell Mol Med 13:2899-910 |
