LDL SIZE DISTRIBUTION IN RELATION TO INSULIN SENSITIVITY AND LIPOPROTEIN PATTERN IN YOUNG AND HEALTHY-SUBJECTS

OBJECTIVE - Smaller LDL particles are associated with an increased ris k for coronary artery disease and have been found predominantly in sub jects with the insulin resistance syndrome. Although insulin resistanc e has been suggested to be a basic defect, little is known about the r elation between this predisposing factor (and associated metabolic dis turbances) and LDL size distribution in young and metabolically health y subjects. In the present study, we investigated the relation between insulin sensitivity, lipoprotein distribution, and LDL patterns in yo ung adults to increase the understanding of the development of metabol ic risk factors in an early phase of the life span. RESEARCH DESIGN AN D METHODS - Young, clinically healthy subjects (n = 50; age 21.1-30.6 years) were enrolled in the study. Glucose metabolism was characterize d by peripheral insulin sensitivity assessed by a hyperinsulinemic-eug lycemic clamp and by levels of fasting insulin, C-peptide, and glucose . Lipoproteins were measured, and LDL fractions were additionally char acterized by the diameter of the major LDL peak, estimated by 2-16% po lyacrylamide gradient gel electrophoresis. Cholesterol ester transfer was estimated with a fluorescent spectroscopic method that measures th e transfer of fluorescent cholesteryl linoleate between exogenous dono r and acceptor particles. In this assay system, cholesterylester trans fer protein (CETP) activity was only influenced by the plasma CETP con centration therefore reflecting more likely the CETP mass. RESULTS - I n the entire study group, 47 subjects had IDL phenotype A (LDL diamete r >25.75 nm) and 3 subjects had an intermediate phenotype (25.50-25.75 nm). An interrelation between LDL size and LDL triglyceride (LDL-TG) per apolipoprotein (apo) B (Spearman's rank correlation analysis; r = -0.78; P < 0.001) or LDL cholesterol ester (CE) per apoB (r = 0.58, P < 0.001) was found, and 39% of the plasma samples studied were charact erized by a monodispersed LDL pattern. Furthermore, LDL diameters corr elated negatively with total TGs (men: r = -0.52, P < 0.001; women: u = -0.61, P < 0.001) and positively with insulin sen sitivity (total po pulation: r = 0.54, P < 0.001). In addition, LDL size was inversely re lated to the [VLDL + LDL cholesterol (CH)]/HDL-CH ratio and positively to the HDL-CE/TG ratio, which were both related vice versa to CETP ac tivity levels. A direct relation between CETP activity levels and LDL size or composition was not observed. In a linear regression analysis including parameters of lipoprotein metabolism (TG, HDL cholesterol, C ETP activity level), glucose metabolism (insulin sensitivity fasting i nsulin), and sex, only TGs predicted significantly for 62% of LDL size variability. If the total study population was evaluated according to quintiles of insulin sensitivity increasing TGs (analysis of variance , Scheffe test; P < 0.05) and CETP activitiy levels (P < 0.05) were co mbined with decreasing LDL particle diameters (P < 0.05) and with a pr eponderance of a monodispersed LDL pattern (60%) in the most insulin-r esistant group. CONCLUSIONS - Among parameters of the lipoprotein and glucose metabolism, total TG is the single most important factor affec ting LDL size variability, even in young adults. Ii the study populati on is evaluated according to insulin sensitivity, lipoprotein pattern is altered in a more atherogenic manner in the most insulin-resistant subjects. In this group, increasing TG and CETP activity levels are as sociated with decreasing LDL particle diameters and preponderance of a monodispersed LDL pattern. Although increasing CETP levels are combin ed with this particular lipoprotein profile, a direct relation to LDL size and composition is not found.