{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:43:11Z","timestamp":1788266591978,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T00:00:00Z","timestamp":1656979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Although ceramides are involved in the pathophysiology of cardiovascular disease and other inflammation-associated disorders, there is a paucity of data on the association between plasma ceramides and inflammatory biomarkers in type 2 diabetes mellitus (T2DM). Therefore, we explored whether there was an association between plasma leucine-rich \u03b1-2 glycoprotein 1 (LRG1) concentrations (i.e., a novel proinflammatory signaling molecule) and specific plasma ceramides in postmenopausal women with T2DM. Methods: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [plasma Cer(d18:1\/16:0), Cer(d18:1\/18:0), Cer(d18:1\/20:0), Cer(d18:1\/22:0), Cer(d18:1\/24:0) and Cer(d18:1\/24:1)], amongst 99 Caucasian postmenopausal women with non-insulin-treated T2DM (mean age 72 \u00b1 8 years, mean hemoglobin A1c 6.9 \u00b1 0.7%), who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramide and LRG1 concentrations were measured with a targeted liquid chromatography-tandem mass spectrometry assay and a Milliplex\u00ae MAP human cardiovascular disease magnetic bead kit, respectively. Results: In linear regression analyses, higher plasma LRG1 levels (1st tertile vs. 2nd and 3rd tertiles combined) were associated with higher levels of plasma Cer(d18:1\/16:0) (standardized \u03b2 coefficient: 0.289, p = 0.004), Cer(d18:1\/18:0) (standardized \u03b2 coefficient: 0.307, p = 0.002), Cer(d18:1\/20:0) (standardized \u03b2 coefficient: 0.261, p = 0.009) or Cer(d18:1\/24:1) (standardized \u03b2 coefficient: 0.343, p &lt; 0.001). These associations remained significant even after adjusting for age, body mass index, systolic blood pressure, total cholesterol level, hemoglobin A1c, insulin resistance and statin use. Conclusions: The results of our pilot exploratory study suggest that higher plasma LRG1 concentration was associated with higher levels of specific high-risk plasma ceramide molecules in elderly postmenopausal women with metabolically well-controlled T2DM, even after adjusting for known cardiovascular risk factors and other potential confounding variables.<\/jats:p>","DOI":"10.3390\/biom12070943","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T10:21:33Z","timestamp":1657016493000},"page":"943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Association between Higher Circulating Leucine-Rich \u03b1-2 Glycoprotein 1 Concentrations and Specific Plasma Ceramides in Postmenopausal Women with Type 2 Diabetes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-6329","authenticated-orcid":false,"given":"Alessandro","family":"Mantovani","sequence":"first","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Csermely","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sani","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Beatrice","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziana","family":"Petracca","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Lunardi","sequence":"additional","affiliation":[{"name":"Clinical Analysis Laboratory and Transfusion Medicine & Clinical Pharmacology, \u201cIRCCS Sacro Cuore-Don Calabria\u201d Hospital, 37024 Negrar, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bonapace","sequence":"additional","affiliation":[{"name":"Division of Cardiology, \u201cIRCCS Sacro Cuore-Don Calabria\u201d Hospital, 37024 Negrar, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9523-9054","authenticated-orcid":false,"given":"Giuseppe","family":"Lippi","sequence":"additional","affiliation":[{"name":"Section of Clinical Biochemistry, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4325-3900","authenticated-orcid":false,"given":"Giovanni","family":"Targher","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.3389\/fimmu.2018.02160","article-title":"Inflammation, a double-edge sword for cancer and other age-related diseases","volume":"9","author":"Gupta","year":"2018","journal-title":"Front. 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