Oxidized LDL immune complexes and coronary artery calcification in type 1 diabetes

Atherosclerosis. 2011 Feb;214(2):462-7. doi: 10.1016/j.atherosclerosis.2010.11.012. Epub 2010 Nov 17.

Abstract

Objective: Oxidized LDL (oxLDL) and oxLDL antibodies form immune complexes (IC) that reflect essential components in the development of atherosclerosis: dyslipidemia, oxidative stress and induction of a pro-inflammatory humoral immune response. We measured oxLDL in IC (oxLDL-IC) isolated from patients with type 1 diabetes to assess the relationship between oxLDL-IC and coronary artery calcification (CAC).

Methods: OxLDL was measured in IC isolated from baseline samples from a subgroup of 476 patients of the Diabetes Control and Complications Trial (DCCT). CAC was determined by computed tomography (CT) 11-20 years later. Multivariable log-binomial regression models were used to estimate the risk ratios associated with having a high CAC score with an increase of 1 standard deviation (SD) of the natural logarithm of oxLDL-IC.

Results: Multivariable regression models indicate that a 1 SD increase in the levels of oxLDL-IC was associated with a 37% increase in the risk of having high CAC score (RR=1.36; 95% CI: 1.12-1.67) at follow-up after adjustment for DCCT treatment group, retinopathy/AER groups, gender and CT scanning site as well as baseline age, diabetes duration and HbA1C %. Further adjustment for smoking status, blood pressure and LDL resulted in a risk ratio of 1.23 (95% CI: 1.01-1.50) which remained statistically significant indicating that baseline oxLDL-IC is independently associated with the development of CAC.

Discussion: Increased levels of oxLDL-IC are associated with the development of coronary calcification. This observation reinforces previously published clinical and experimental data demonstrating that oxLD-IC has pro-inflammatory and proatherogenic properties.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antigen-Antibody Complex / blood*
  • Calcinosis / blood*
  • Calcinosis / diagnostic imaging
  • Chi-Square Distribution
  • Coronary Angiography / methods
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / immunology*
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / immunology*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Immunity, Humoral*
  • Insulin / therapeutic use
  • Lipoproteins, LDL / blood
  • Lipoproteins, LDL / immunology*
  • Regression Analysis
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Tomography, X-Ray Computed
  • United States
  • Young Adult

Substances

  • Antigen-Antibody Complex
  • Hypoglycemic Agents
  • Insulin
  • Lipoproteins, LDL
  • oxidized low density lipoprotein