Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes

Kelly J Hunt; Nathaniel Baker; Patricia Cleary; Jye-Yu Backlund; Timothy Lyons; Alicia Jenkins; Gabriel Virella; Maria F Lopes-Virella; DCCT/EDIC Research Group

doi:10.1016/j.atherosclerosis.2013.09.027

Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes

Kelly J Hunt, Nathaniel Baker, Patricia Cleary, Jye-Yu Backlund, Timothy Lyons, Alicia Jenkins, Gabriel Virella, Maria F Lopes-Virella, DCCT/EDIC Research Group

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

Abstract

Objective

Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease.

Methods

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 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intima–medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12.

Results

OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r = 0.66–0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT ≥ 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81).

Conclusion

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.

Original language	English
Pages (from-to)	315-322
Journal	Atherosclerosis
Volume	231
Issue number	2
Early online date	11 Oct 2013
DOIs	https://doi.org/10.1016/j.atherosclerosis.2013.09.027
Publication status	Published - Dec 2013

Bibliographical note

Published by Elsevier Ireland Ltd.

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.atherosclerosis.2013.09.027Licence: Unspecified

Cite this

@article{48fb37624e344c4b96b604b329bbcf16,

title = "Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes",

abstract = "Objective Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease. Methods 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 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intima–medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Results OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r = 0.66–0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT ≥ 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81). Conclusion 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.",

author = "Hunt, {Kelly J} and Nathaniel Baker and Patricia Cleary and Jye-Yu Backlund and Timothy Lyons and Alicia Jenkins and Gabriel Virella and Lopes-Virella, {Maria F} and {DCCT/EDIC Research Group}",

note = "Published by Elsevier Ireland Ltd.",

year = "2013",

month = dec,

doi = "10.1016/j.atherosclerosis.2013.09.027",

language = "English",

volume = "231",

pages = "315--322",

journal = "Atherosclerosis",

issn = "0021-9150",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

TY - JOUR

T1 - Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes

AU - Hunt, Kelly J

AU - Baker, Nathaniel

AU - Cleary, Patricia

AU - Backlund, Jye-Yu

AU - Lyons, Timothy

AU - Jenkins, Alicia

AU - Virella, Gabriel

AU - Lopes-Virella, Maria F

AU - DCCT/EDIC Research Group

N1 - Published by Elsevier Ireland Ltd.

PY - 2013/12

Y1 - 2013/12

N2 - Objective Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease. Methods 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 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intima–medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Results OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r = 0.66–0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT ≥ 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81). Conclusion 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.

AB - Objective Over 90% of modified LDL in circulation is associated to specific antibodies circulating as part of immune complexes (IC); however, few studies have examined their relationship with cardiovascular disease. Methods 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 467 individuals with type 1 diabetes who participated in the Diabetes Control and Complications Trial (DCCT) and the Epidemiology of Diabetes Interventions and Complications (EDIC) study. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured at DCCT closeout. Internal carotid intima–medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Results OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were significantly correlated with age, lipid levels, blood pressure levels and albumin excretion rates. Levels of oxLDL, AGE-LDL and MDA-LDL in isolated LDL-IC were highly inter-correlated (r = 0.66–0.84, P < 0.0001). After adjusting for cardiovascular risk factors individuals in the upper quartile of oxLDL-IC had a 2.98-fold increased odds (CI: 1.34, 6.62) of having IMT ≥ 1.00 mm and had a 5.13-fold increased odds (CI: 1.98, 13.3) of having significant IMT progression, relative to those in the lowest quartile. Parallel odds ratios for AGE-LDL-IC were 2.95 (CI: 1.37, 6.34) and 3.50 (CI: 1.38, 8.86), while results for MDA-LDL-IC were 1.76 (0.87, 3.56) and 2.86 (1.20, 6.81). Conclusion 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.

U2 - 10.1016/j.atherosclerosis.2013.09.027

DO - 10.1016/j.atherosclerosis.2013.09.027

M3 - Article

C2 - 24267245

SN - 0021-9150

VL - 231

SP - 315

EP - 322

JO - Atherosclerosis

JF - Atherosclerosis

IS - 2

ER -

Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

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