Levels of Oxidized LDL and Advanced Glycation End Products–Modified LDL in Circulating Immune Complexes Are Strongly Associated With Increased Levels of Carotid Intima-Media Thickness and Its Progression in Type 1 Diabetes
- Maria F. Lopes-Virella1,2,
- Kelly J. Hunt1,
- Nathaniel L. Baker1,
- John Lachin3,
- David M. Nathan4,
- G. Virella5 and
- the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group
- 1Department of Medicine, Medical University of South Carolina, Charleston, South Carolina
- 2Ralph A. Johnson Veterans Affairs Medical Center, Charleston, South Carolina
- 3The Biostatistics Center, George Washington University, Washington, District of Columbia
- 4Harvard Medical School and Massachusetts General Hospital, Department of Microbiology and Immunology, Boston, Massachusetts
- 5Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina
- Corresponding author: Maria F. Lopes-Virella, .
OBJECTIVE High cholesterol levels in circulating immune complexes (IC), surrogate markers of modified LDL, are associated with increased carotid intima-media thickness (IMT) and cardiovascular events in type 1 diabetes. Different modifications of LDL are involved in IC formation, but which of these are predictive of vascular events is not known. Therefore, we measured oxidized LDL (oxLDL), advanced glycation end products–modified LDL (AGE-LDL), and malondialdehyde-modified LDL (MDA-LDL) in IC and determined their relationship with increased carotid IMT and compared the strength of the association with that observed with conventional risk factors.
RESEARCH DESIGN AND METHODS Levels of oxLDL, AGE-LDL, and MDA-LDL were measured in circulating IC isolated from sera of 479 patients of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort, collected at baseline. Internal and common carotid IMT were measured 8 and 14 years later by DCCT/EDIC.
RESULTS OxLDL, AGE-LDL, and MDA-LDL levels in circulating IC were significantly correlated with diabetes duration, BMI, and lipid and blood pressure, but not with age. Multivariate logistic regression models indicated that individuals in the highest versus lowest quartile of oxLDL and AGE-LDL in IC had a 6.11-fold [confidence interval (CI) 2.51–14.8] and a 6.4-fold (CI 2.53–16.2) increase in the odds of having high carotid IMT, respectively, after adjusting for conventional risk factors. Parallel analyses resulted in odds ratios of 2.62 (CI 1.24, 5.55) for LDL-C, 1.45 (CI 0.69, 3.03) for diastolic blood pressure, and 2.33 (CI 1.09, 4.99) for A1C.
CONCLUSIONS OxLDL and AGE-LDL in circulating IC were significantly associated with progression and increased levels of carotid IMT in type 1 diabetes.
This article contains supplementary data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db10-0915/-/DC1.
*A complete list of Epidemiology of Diabetes Interventions and Complications Research Group participants is available in the supplementary data online.
- Received June 30, 2010.
- Accepted October 18, 2010.
- © 2011 by the American Diabetes Association.
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