@article{984bde0cc14a453fbe7ea634708b3233,
title = "High levels of oxidized LDL in circulating immune complexes are associated with increased odds of developing abnormal albuminuria in Type 1 diabetes",
abstract = "Background. Modified low-density lipoprotein (LDL) immune complexes (IC) have proinflammatory properties and play a role in albuminuria development. Methods. We measured oxidized LDL (oxLDL) and advanced glycation end-product (AGE)-LDL in IC isolated from sera of Type 1 diabetic subjects followed for 14-20 years and studied their association with abnormal albuminuria. Patients with albumin excretion rates (AER) <40 mg/24 h at baseline and follow-up (n = 302) were deemed resistant to developing abnormal albuminuria. Patients with AER <40 mg/24 h at baseline whose AER levels progressed to >40 mg/24 h were considered prone to abnormal albuminuria (n = 185), those who progress to AER >299 mg/24 h were considered as having macroalbuminuria (n = 57). The odds of developing abnormal albuminuria were estimated by logistic regression based on natural log-transformed levels of oxLDL and AGE-LDL in IC and stratified by baseline AER decile. Results. OxLDL and AGE-LDL were significantly higher in IC isolated from patients progressing to abnormal albuminuria. In unadjusted conditional logistic analysis, an increase of 1 SD in oxLDL and AGE-LDL levels in IC significantly increased the odds ratio (OR) for development of macroalbuminuria, respectively, by a factor of 2.5 and 1.8 (P < 0.001, P = 0.008). The increased odds of developing macroalbuminuria remained significant when adjusted for treatment group, diabetes duration, retinopathy, baseline hemoglobin A1c and LDL (OR = 2.5 and 1.8, respectively, P < 0.01).Conclusion.Higher levels of oxLDL and AGE-LDL in circulating IC were associated with increased odds to develop abnormal albuminuria.",
keywords = "albuminuria, diabetic nephropathy, immune complexes, modified lipoproteins",
author = "Lopes-Virella, {Maria F.} and Carter, {Rickey E.} and Baker, {Nathaniel L.} and John Lachin and Gabriel Virella",
note = "Funding Information: Fasting serum samples obtained during DCCT/EDIC were sent to the DCCT/EDIC central laboratory for standard lipid analysis. Aliquots of these samples were archived for future research purposes. In 1999– 2000, as part of Medical University of South Carolina Program Project Grant funded by the National Institutes of Health/Juvenile Diabetes Foundation, serum samples collected during DCCT were provided by the DCCT/EDIC Coordinating Center and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to complement the serum samples collected during EDIC. The serum samples had been stored at −70° C and refreezing effects were minimized by preparing aliquots of the serum when thawed for the first time and using a new frozen aliquot for each new test performed. The IRB at Medical University of South Carolina and all participating DCCT/EDIC centers approved the sample collection procedures. Written informed consent was obtained from all participants. Funding Information: The DCCT/EDIC was sponsored through research contracts from the Division of Diabetes, Endocrinology and Metabolic Diseases (NIDDK) of the NIH. Additional support was provided by the National Center for Research Resources through the GCRC program and by Genentech Inc through a Cooperative Research and Development Agreement with the NIDDK. Funding Information: Acknowledgements. This work was supported by a Program Project funded by the National Institutes of Health/NHLBI (PO1 HL 55782), by an RO1 Grant funded by NIH/NIDDK (R01 DK081352) and by a Juvenile Diabetes Foundation Grant (2006-49). The work was also supported by the Research Service of the Ralph H. Johnson Department of the Veterans Affairs Medical Center. The contents of this manuscript do not represent the views of the Department of Veterans Affairs or the United States Government.",
year = "2012",
month = apr,
doi = "10.1093/ndt/gfr454",
language = "English (US)",
volume = "27",
pages = "1416--1423",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "4",
}