LDL particle size in relation to insulin, proinsulin, and insulin sensitivity - The insulin resistance atherosclerosis study

OBJECTIVE - LDI particles are heterogeneous in terms of size and density: s mall dense LDL particles are considered more atherogenic than larger LDL pa rticles. The aim of this study was to investigate the interrelationships am ong LDL size, insulin, proinsulin (intact and split), and insulin sensitivi ty in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS- Insulin sensitivity was assessed by a frequent ly sampled intravenous glucose tolerance lest with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detec table cross-reactivity with insulin, and LDL size was determined by gradien t-gel electrophoresis. RESULTS - In univariate analyses. LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin -to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0 .0001). In a multivariate regression model (adjusted for age, BMI, ethnicit y, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.00 01), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantl y inversely related to proinsulin in men (P = 0.005 and P = 0.04 after furt her adjustment for the glucose tolerance status), but not in women (P > 0.1 5). CONCLUSIONS - We found an inverse relation of proinsulin to LDL particle si ze in a large tri-ethnic population with varying degrees of glucose toleran ce. This relation was independent of age, BMI, and triglyceride and HDL cho lesterol concentrations, and was more pronounced in men than in women.