Markers & Mechanisms for Pre-Eclampsia in Women with Type 1 Diabetes

Principal Investigator: Timothy J. Lyons, MD, FRCP

Abstract:

Our primary goal is to define the roles of dyslipidemia and oxidative stress in accelerating macrovascular disease (atherosclerosis) in diabetes.  Microvascular disease (nephropathy and retinopathy) will be studied as secondary end-points.  We will continue (and expand) our longitudinal and cross-sectional studies of the DCCT/EDIC cohort of Type 1 diabetic patients. This cohort is the largest and best-characterized group of Type 1 diabetic patients in the world.  Though still relatively young, it has provided exciting data during the first funding period of the Program Project (1996-present).  To obtain a higher "hard" event rate (myocardial infarction, stroke etc.) and to study the more common form of diabetes, we will add a Type 2 diabetes cohort from the VA Cooperative Trial "Glycemia and Complications in Diabetes, Type 2".  This prospective trial commences October 2000, and as in the DCCT, patients will be randomized to intensive and standard glycemic control.  The VA trial provides us with the opportunity to study patients during the randomized portion of the study (in the DCCT, randomization finished in 1993).  We will also perform basic science studies to investigate hypotheses we have developed over the past four years relating to dyslipidemia, oxidative stress and atherogenesis in diabetes.  These studies, in collaboration with the other Projects and Cores and the Coordinating Centers of both studies, will greatly increase our understanding of the complex multi-factorial mechanisms underlying vascular disease in both types of diabetes.

Specific Aims:

1. To define the role of dyslipidemia in the vascular complications of Type 1 and Type 2 diabetes. We will perform comprehensive lipoprotein analyses, including Nuclear Magnetic Resonance (NMR) lipoprotein profiles, levels of apolipoproteins, Lipoprotein(a), and studies of lipoprotein-associated enzymes.

2. To define the roles of oxidative stress, inflammation, and homocysteine in the vascular complications of Type 1 and Type 2 diabetes.

3. To determine the effect of lipoprotein associated enzymes on lipoprotein subclass distribution.

4. To determine functional characteristics of LDL, HDL, and their subclasses from Type 1 and Type 2 diabetic patients and control subjects in studies using human aortic endothelial cells (HAEC) and human red blood cell (RBC) membranes.

 Participant Inclusion Criteria:

Participant Compensation:

Contact Information:

Yong “Jeremy” Wu. (405) 271-5896 X 48466 or yong-wu@ouhsc.edu