Atherogenic Lipid Phenotype and Lipoprotein (a) in Diabetes

Abstract

The atherogenic lipid phenotype (ALP) and lipoprotein (a) [Lp(a)] are strongly implicated emerging risk factors for cardiovascular (CV) disease among diabetic patients. The ALP and Lp(a) have been strongly linked to CV disease by epidemiological prevalence, risk, and interventional studies. The origins of ALP, especially small, dense low-density lipoprotein (LDL) and reduced levels of total high-density lipoprotein (HDL) cholesterol and HDL2, are related to increased levels of triglyceride and increased hepatic production of very low-density lipoprotein 1 (VLDL1). Remodeling of VLDL1 in the circulation ultimately results in the formation of small, dense LDL and low levels of HDL. These molecular events are often tightly linked, so patients have a composite or profile of abnormalities including increased triglycerides, small LDL particle size, a preponderance of small, dense LDL particle mass, and diminished levels of total HDL cholesterol and HDL fraction 2 (HDL2). Methods used to measure these lipids center around ultracentrifugation, gel electrophoresis and nuclear magnetic resonance technology. The diagnostic criteria for these emerging CV risk factors remain somewhat ambiguous and require further clarification. Treatment of ALP and Lp(a) is currently quite effective according to data derived from preliminary studies. Therapies such as niacin products, fenofibrate, and atorvastatin are successful, but combination therapy with extended-release niacin and atorvastatin appears to be the best current treatment.