Abstract
Many studies have demonstrated a relationship between modified LDL and cardiovascular disease. Nonetheless, few studies have examined the relationship between modified LDL immune complexes (IC) and cardiovascular disease, even though the majority of modified LDL in circulation is bound to IC. We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in individuals with type 1 diabetes. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured in a subgroup of 459 patients participating in the Diabetes Control and Complications Trial (DCCT) and it’s follow up study the Epidemiology of Diabetes Interventions and Complications (EDIC). Internal carotid intima-medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Levels of oxLDL-IC, AGE-LDL-IC and MDA-LDL-IC were moderately correlated with lipid levels [i.e., rho<0.32], but not with age. Modified LDL-IC significantly predicted having elevated internal carotid IMT (i.e., IMT ≥1.00 mm) as well as progression of IMT defined as being in the upper quintile of change from EDIC year 1 to 12 after adjusting for DCCT treatment group [intensive vs. conventional], retinopathy cohort [primary prevention vs. secondary intervention], age, gender, diabetes duration, albumin excretion rate, LDL, HDL, SBP, smoking status and IMT reader (Table). Relative to those in the lowest quartile, individuals in the upper quartile of oxLDL-IC had a 3.7-fold increased odds (CI: 1.72, 7.94) of having IMT ≥ 1.00 mm and had a 6.1-fold increased odds (CI: 2.57, 14.6) of having significant IMT progression. Parallel odds ratios for AGE-LDL-IC were 3.26 (CI: 1.57, 6.79) and 5.31 (CI: 2.23, 12.6), while results for MDA-LDL-IC were not as strong. Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intima-medial thickening in patients with type 1 diabetes.
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