Increased Small Dense LDL and Decreased Paraoxonase Enzyme Activity Reveals Formation of an Atherogenic Risk in Streptozotocin-Induced Diabetic Guinea Pigs

This study aimed to investigate LDL subfraction distribution as well as serum cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), and paraoxonase (PON1) activity in streptozotocin-induced diabetic guinea pigs. Materials/Methods. Guinea pigs were given a single intraperitoneal (ip) injection of streptozotocin (STZ) and animals having fasting blood glucose levels greater than 200？mg/dl, were considered diabetic. Protein levels of LCAT and CETP were determined via ELISA. Paraoxonase activity was measured kinetically by the formation of phenol while LDL subfraction analysis was done by disc polyacrylamide gel electrophoresis. Results. Plasma glucose and high-density lipoprotein (HDL) cholesterol were significantly increased while total cholesterol and LDL cholesterol were significantly decreased in diabetic guinea pigs compared to controls. LDL subfraction analysis revealed a significant decrease in nonatherogenic LDL-2 subfraction and a significant increase in atherogenic LDL-4 subfraction in diabetic guinea pigs compared to controls. Plasma CETP and PON1 levels were significantly decreased while LCAT showed no significant difference in diabetic guinea pigs compared to controls. Conclusion. Decreased non-atherogenic LDL-1, LDL-2 subfractions, increased small dense LDL-4 subfraction, and decreased PON1 activity, reveals formation of an atherogenic risk in diabetic guinea pigs. Decrease in CETP levels supports the observed increase in HDL cholesterol levels in diabetic guinea pigs. 1. Introduction Type 1 diabetic patients, even those who are normolipidemic, present increased risk of premature atherosclerosis. This suggests that normal values in lipid profile can mask alterations in the composition and distribution of the denser LDL subclasses, whose characteristics make them potentially more atherogenic [1]. The association between LDL cholesterol levels and ischemic heart disease (IHD) is well established; however, it has been shown that 35% of patients with a cholesterol level less than 200？mg/dl develop IHD [2]. Circulating LDL particles are heterogeneous with respect to size, density, composition, and physicochemical properties [3]. Using gradient gel electrophoretic analysis of isolated LDL, two distinct LDL phenotypes have been documented [4]. Pattern B shows a predominance of small, dense LDL particles, while pattern A reveals a higher proportion of large, more buoyant LDL particles. Irrespective of the approach used to characterize LDL particles and of the case definition, dense LDL particles were more prevalent