{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:44:39Z","timestamp":1784547879074,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness","award":["PI21\/00116"],"award-info":[{"award-number":["PI21\/00116"]}]},{"name":"Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness","award":["PI22\/00616"],"award-info":[{"award-number":["PI22\/00616"]}]},{"name":"Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness","award":["DEM21-PIM02"],"award-info":[{"award-number":["DEM21-PIM02"]}]},{"name":"European Development Regional Fund \u2018A way to achieve Europe\u2019 (ERDF)","award":["PI21\/00116"],"award-info":[{"award-number":["PI21\/00116"]}]},{"name":"European Development Regional Fund \u2018A way to achieve Europe\u2019 (ERDF)","award":["PI22\/00616"],"award-info":[{"award-number":["PI22\/00616"]}]},{"name":"European Development Regional Fund \u2018A way to achieve Europe\u2019 (ERDF)","award":["DEM21-PIM02"],"award-info":[{"award-number":["DEM21-PIM02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 \u00b1 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing\u2019s tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R\u00b2 = 0.178, p &lt; 0.001), the main determinants of CAN included isoleucine [Exp(\u03b2) = 0.972 (95% CI 0.952; 0.003)], age [Exp(\u03b2) = 1.031 (95% CI 1.010; 1.053)], A1c [Exp(\u03b2) = 1.361 (95% CI 1.058; 1.752)], and microangiopathy [Exp(\u03b2) = 2.560 (95% CI 1.372; 4.778)]. Sex influenced LMWM profiles, with over half of the metabolites differing between men and women. However, no interactions were found between CAN and sex, or between sex, age, and CAN, on metabolomics profiles. Our findings suggest an association between CAN and LMWM levels in T1D. The sexual dimorphism observed in amino acid metabolites was unaffected by the presence of CAN.<\/jats:p>","DOI":"10.3390\/metabo14080436","type":"journal-article","created":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T15:24:16Z","timestamp":1722957856000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3168-7856","authenticated-orcid":false,"given":"Mar\u00eda Rosa","family":"Insenser","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"}],"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"}]},{"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"}]},{"given":"Sara de Lope","family":"Qui\u00f1ones","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"}],"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Samino","sequence":"additional","affiliation":[{"name":"Biosfer Teslab, CIBERDEM, 43206 Tarragona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0116-9145","authenticated-orcid":false,"given":"N\u00faria","family":"Amig\u00f3","sequence":"additional","affiliation":[{"name":"Biosfer Teslab, CIBERDEM, 43206 Tarragona, Spain"},{"name":"Institut d\u2019Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV), Department of Basic Medical Sciences, Universitat Rovira i Virgili (URV), 43002 Tarragona, 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\/0000-0003-1398-5489","authenticated-orcid":false,"given":"Tom","family":"Fiers","sequence":"additional","affiliation":[{"name":"Laboratory for Hormonology and Department of Endocrinology, Ghent University Hospital, 9000 Ghent, Belgium"}],"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"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2424","DOI":"10.1161\/CIR.0000000000000343","article-title":"Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus: A Scientific Statement From the American Heart Association","volume":"132","author":"Regensteiner","year":"2015","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e002480","DOI":"10.1136\/bmjdrc-2021-002480","article-title":"Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and 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