Alterations in dense LDL subfractions in normolipidemic IDDM patients

Low density lipoproteins (LDL) of human plasma, consist of a continuum of particles subclasses with distinct physicochemical, immunological and hydrodynamic characteristics. Such structural differences are intimately linked to atherogenesis. The current study was designated to investigated the LDL subclasses profile in 12 normolipidemic IDDM patients, and compare it with 11 healthy controls. Four plasma LDL subfractions were isolated by sequential ultracentrifugation in the density range (1.025-1.063 g/ml) and were characterized by their content of free and esterified cholesterol, triglycerides, phospholipids, and proteins. The net electrical charge was evaluated. Plasma concentration of the two denser LDL subfractions were higher in IDDM patients vs control subjects, due to an increase in cholesterol (free and esterified) and phospholipids, while more buoyant subfractions in the two groups were not different. In IDDM patients the LDL profile was skewed towards the dense subclasses LDL-III and LDL-IV, being significant this increase for LDL-IV: 22.3 +/- 5.2 vs 18.3 +/- 4.0%, p < 0.05, X +/- DS. In the healthy controls the LDL profile was skewed toward the lighter subclasses (LDL-I and LDL-II), being significant for LDL-II: 30.0 +/- 4.3 vs 23.3 +/- 4.2%, p < 0.005. Diabetic patients, even those who are normolipidemic, present increased risk of premature atherosclerosis. This suggest that normal values in lipid and lipoprotein profile can mask deeper alterations, such as changes in the composition and distribution of the denser subclasses, whose characteristics make them potentially more atherogenic. Despite the apparently normolipidemic status, dense LDL particles considered to be atherogenic, are increased in IDDM patients.