There is increasing clinical interest in a common human atherogenic lipoprotein phenotype (ALP) characterized by a moderate increase in plasma triglycerides, a decrease in high density lipoprotein (HDL) cholesterol and the prevalence of small dense LDL. ALP is commonly observed in type 2 diabetes mellitus and small dense LDL may be the unifying marker of diabetic dyslipidemia. LDL particles are heterogeneous and have been grouped, based on their size and density, into four major subclasses designated LDL I through IV, from the largest, most buoyant to the smallest, most dense. LDL subclasses can be measured by gradient gel electrophoresis (GGE) and it has been demonstrated that GGE is capable of identifying patients with enhanced risk for cardiovascular disease in addition to the more traditional lipid values. Thus, persons with a LDL main peak < 257 Å (so called “pattern B phenotype”) demonstrate a three to seven fold increased risk for coronary heart disease compared to the “pattern A phenotype” (LDL main peak > 264 Å).The significance of small dense LDL in patients with diabetes type 2 as a clinical marker to assess cardiovascular risk and predict progression of atherosclerosis has not been established so far. Supported by our preliminary results that LDL size in diabetes type 2 with coronary artery disease (CAD) is smaller compared to diabetes type 2 patients without CAD and good correlations of LDL size with pro- and antiatherogenic lipids and apolipoproteins, we aim to perform a prospective study to compare the value of LDL subclass measurement in diabetes type 2 patients with other lipid, non-lipid and clinical risk factors for cardiovascular disease. The proposed project is an ongoing clinical project (started in 2003) in type 2 diabetes patients, the relative distribution of lipoprotein subclasses, specifically small dense LDL is being measured by gradient gel electrophoresis (GGE). Cardiovascular risk factors are assessed by questionnaires, physical examination (e.g. BMI, blood pressure), measurement of the traditional lipids, apolipoprotein composition, lipoprotein (a) and high sensitivity C reactive protein as a marker of inflammation. Common carotid artery intima media thickness as a marker of atherosclerosis is being measured by B-mode ultrasound. All measurements will be repeated after one, three and six years. Prospective data is needed to weight the clinical significance of LDL size for the development of atherosclerosis and may be of significant clinical value for early identification of diabetes type 2 patients at highest risk for cardiovascular disease.