{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:45:54Z","timestamp":1784547954723,"version":"3.55.0"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T00:00:00Z","timestamp":1736985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III","award":["PI22\/00616"],"award-info":[{"award-number":["PI22\/00616"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Introduction: This study aimed to evaluate whether glycoprotein and lipoprotein lipidomics profiles could enhance a clinical predictive model for carotid subclinical atherosclerosis in patients with type 1 diabetes (T1D). Additionally, we assessed the influence of cardiac autonomic neuropathy (CAN) on these predictive models. Methods: We conducted a cross-sectional study including 256 patients with T1D. Serum glycoprotein and lipoprotein lipidomics profiles were determined using 1H-NMR spectroscopy. Subclinical atherosclerosis was defined as carotid intima-media thickness (cIMT) \u2265 1.5 mm. CAN was identified using the Clarke score. Predictive models were built and their performance evaluated using receiver operating characteristic curves and cross-validation. Results: Subclinical atherosclerosis was detected in 32% of participants. Patients with both CAN and atherosclerosis were older, had a longer duration of diabetes, and were more likely to present with bilateral carotid disease. Clinical predictors such as age, duration of diabetes, and smoking status remained the strongest determinants of subclinical atherosclerosis [AUC = 0.88 (95%CI: 0.84\u20130.93)]. While glycoprotein and lipoprotein lipidomics profiles were associated with atherosclerosis, their inclusion in the clinical model did not significantly improve its diagnostic performance. Stratification by the presence of CAN revealed no impact on the model\u2019s ability to predict subclinical atherosclerosis, underscoring its robustness across different risk subgroups. Conclusions: In a cohort of patients with T1D, subclinical atherosclerosis was strongly associated with traditional clinical risk factors. Advanced glycoprotein and lipoprotein lipidomics profiling, although associated with atherosclerosis, did not enhance the diagnostic accuracy of predictive models beyond clinical variables. The predictive model remained effective even in the presence of CAN, highlighting its reliability as a screening tool for identifying patients at risk of subclinical atherosclerosis.<\/jats:p>","DOI":"10.3390\/metabo15010055","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T06:46:10Z","timestamp":1737009970000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling Silent Atherosclerosis in Type 1 Diabetes: The Role of Glycoprotein and Lipoprotein Lipidomics, and Cardiac Autonomic Neuropathy"],"prefix":"10.3390","volume":"15","author":[{"given":"Sara","family":"de Lope Qui\u00f1ones","sequence":"first","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-4237","authenticated-orcid":false,"given":"Manuel","family":"Luque-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5626-0218","authenticated-orcid":false,"given":"Antonio Carlos","family":"Michael Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Radiology, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra","family":"Quintero Tobar","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6061-9751","authenticated-orcid":false,"given":"Jhonatan","family":"Qui\u00f1ones-Silva","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8354-7284","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"Mart\u00ednez Garc\u00eda","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-7856","authenticated-orcid":false,"given":"Mar\u00eda","family":"Insenser Nieto","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4751-3017","authenticated-orcid":false,"given":"Beatriz","family":"Dorado Avenda\u00f1o","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6890-1644","authenticated-orcid":false,"given":"H\u00e9ctor F.","family":"Escobar-Morreale","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9758-9397","authenticated-orcid":false,"given":"L\u00eda","family":"Nattero-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Human Reproduction Research Group, Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS) & Centro de Investigaci\u00f3n Biom\u00e9dica en Red Diabetes y Enfermedades Metab\u00f3licas Asociadas (CIBERDEM), Universidad de Alcal\u00e1, 28034 Madrid, Spain"},{"name":"Department of Endocrinology and Nutrition, Hospital Universitario Ram\u00f3n y Cajal, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.2337\/db08-1543","article-title":"The Presence and Severity of Chronic Kidney Disease Predicts All-Cause Mortality in Type 1 Diabetes","volume":"58","author":"Groop","year":"2009","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/S0140-6736(08)60767-9","article-title":"Type 1 Diabetes, Hyperglycaemia, and the Heart","volume":"371","author":"Retnakaran","year":"2008","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.diabet.2020.09.001","article-title":"Cardiovascular Disease in Type 1 Diabetes: A Review of Epidemiological Data and Underlying Mechanisms","volume":"46","year":"2020","journal-title":"Diabetes 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