A predominant consequence of diabetes mellitus type 2 (DM 2) is accelerated development of atherosclerosis related conditions. Conventional cardiovascular risk factors (CVRF) only explain a portion of the excess risk for atherosclerosis in this population. The overall goals of this project are to test whether novel CVRF are related to the presence and development of atherosclerosis and macrovascular events in DM 2 and to determine whether intensive glucose lowering therapy will reduce the levels of these CVRF. Specific short-term primary aims include determining the cross- sectional relationship between baseline levels and the presence of athero- sclerosis as measured by electron beam computed tomography assessment of coronary artery (CAC) and abdominal aortic calcium (AAC) and the prevalence of clinical macrovascular disease. The investigator proposes to take advantage of the study population and framework of the V A Cooperative study of """"""""Glycemic Control and Complications in DM 2"""""""" to address these questions in an efficient and cost-effective manner. The Cooperative study is a prospective, two-arm, randomized, controlled, multicenter trial to assess the effects of tight glycemic control, achieved through intensification of treatment, on clinical macrovascular and microvascular complications in patients with DM 2 who are in poor glycemic control despite pharmacologic therapy. Cooperative study subjects from multiple sites (340 subjects) will be asked to participate in this additional trial. At their baseline visit, subjects will have additional blood and urine collected for a) VLDL, IDL and LDL subfractions b) measures of in vivo oxidative stress (oxidized-phospholipids on plasma LDL, autoantibodies to epitopes of oxidized LDL, F2-isoprostane levels) c) AGE-LDL levels, and d) markers of endothelial activation/injury (PAI-1, VCAM-1 and ICAM-1) and inflammation (C-reactive protein and fibrinogen). Subjects will also have CAC and AAC determined. After enrollment in the study, participants will have measurements of CVRF repeated at six months. Primary and secondary macrovascular endpoints will be identical to those defined in the VA Cooperative study (Primary: myocardial infarction, cardiovascular death, stroke, congestive heart failure, invasive vascular therapy (coronary or peripheral), and amputation due to ischemic gangrene; Secondary: angina pectoris, transient ischemic attacks, and peripheral artery disease). Statistical methods, depending on the specific aim will include categorical age and sex adjusted analyses, t-tests, and multiple regression models. Long- term (future) aims will include evaluating the prospective relationship of these novel cardiovascular risk factors to the progression of atherosclerosis and the development of macrovascular disease in this same population.
