{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T19:00:57Z","timestamp":1772910057110,"version":"3.50.1"},"reference-count":35,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2019,8,20]],"date-time":"2019-08-20T00:00:00Z","timestamp":1566259200000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01-DK-094176"],"award-info":[{"award-number":["U01-DK-094176"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["U01-DK-094157"],"award-info":[{"award-number":["U01-DK-094157"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:p>We investigated whether the composition of modified forms of LDL in circulating immune complexes (LDL-ICs) was associated with cardiovascular disease (CVD) outcomes, including any CVD, major adverse cardiac and cerebrovascular events (MACCE), myocardial infarction (MI), and coronary artery disease, in type 1 diabetes (T1D). Our results demonstrate that the baseline levels of oxidized LDL (oxLDL), MDA-modified LDL (MDA-LDL), and advanced glycosylation\u2013modified LDL (AGE-LDL) in circulating ICs were associated with the four CVD outcomes in unadjusted models, and adjustment by age and mean HbA1c only resulted in minimal reduction of these associations. After adjustments were made for other cardiovascular risk factors, particularly LDL cholesterol, oxLDL-IC and MDA-LDL-IC remained independently associated with the risk of CVD, and oxLDL-IC was independently associated with the risk of MACCE and MI. In the majority of cases, the baseline levels of modified LDL-IC (measured many years before the occurrence of any CVD event) were associated with the risk of CVD over a 25-year period even after adjustment for other risk factors (including LDL cholesterol). Therefore, modified LDL biomarkers may help identify patients with T1D at high risk for MACCE and CVD events very early in the evolution of the disease, before other signals of disease are apparent.<\/jats:p>","DOI":"10.2337\/db19-0358","type":"journal-article","created":{"date-parts":[[2019,6,19]],"date-time":"2019-06-19T22:25:13Z","timestamp":1560983113000},"page":"1853-1860","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Immune Complexes and the Risk of CVD in Type 1 Diabetes"],"prefix":"10.2337","volume":"68","clinical-trial-number":[{"clinical-trial-number":"nct00360893","registry":"10.18810\/clinical-trials-gov","type":"results"},{"clinical-trial-number":"nct00360815","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5572-1700","authenticated-orcid":false,"given":"Maria F.","family":"Lopes-Virella","sequence":"first","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-7968","authenticated-orcid":false,"given":"Ionut","family":"Bebu","sequence":"additional","affiliation":[{"name":"Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-3587","authenticated-orcid":false,"given":"Kelly J.","family":"Hunt","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Virella","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-1579","authenticated-orcid":false,"given":"Nathaniel L.","family":"Baker","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston, SC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2184-9754","authenticated-orcid":false,"given":"Barbara","family":"Braffett","sequence":"additional","affiliation":[{"name":"Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9838-2841","authenticated-orcid":false,"given":"John M.","family":"Lachin","sequence":"additional","affiliation":[{"name":"Biostatistics Center, The George Washington University, Rockville, MD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the DCCT\/EDIC Research Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2019,6,19]]},"reference":[{"key":"2022031303094999000_B1","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1161\/01.CIR.103.15.1955","article-title":"Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes","volume":"103","author":"Ehara","year":"2001","journal-title":"Circulation"},{"key":"2022031303094999000_B2","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1161\/01.ATV.0000021150.63480.CD","article-title":"Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (AIR Study)","volume":"22","author":"Hulthe","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2022031303094999000_B3","doi-asserted-by":"crossref","first-page":"3395","DOI":"10.2174\/1381612043383188","article-title":"Lipoproteins and diabetic microvascular complications","volume":"10","author":"Jenkins","year":"2004","journal-title":"Curr Pharm Des"},{"key":"2022031303094999000_B4","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3109\/07853890109002058","article-title":"C-reactive protein, fibrinogen, interleukin-6 and tumour necrosis factor-alpha in the prognostic classification of unstable angina pectoris","volume":"33","author":"Koukkunen","year":"2001","journal-title":"Ann Med"},{"key":"2022031303094999000_B5","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1084\/jem.168.3.1041","article-title":"Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. 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