Sphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies

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dc.article.number446
dc.catalogadoryvc
dc.contributor.authorBerkowitz Fiebich Loni
dc.contributor.authorRazquin, Cristina
dc.contributor.authorSalazar Vilches, Cristian Javier
dc.contributor.authorBiancardi Roman, Fiorella Carinna
dc.contributor.authorEstruch, Ramón
dc.contributor.authorRos, Emilio
dc.contributor.authorFitó, Montserrat
dc.contributor.authorCorella, Dolores
dc.contributor.authorCoe, Christopher L.
dc.contributor.authorRyff, Carol D.
dc.contributor.authorRuiz-Canela, Miguel
dc.contributor.authorSalas-Salvado, Jordi
dc.contributor.authorWang, Daniel
dc.contributor.authorHu, Frank B.
dc.contributor.authorDeik, Amy
dc.contributor.authorMartínez-González, Miguel A.
dc.contributor.authorRigotti Rivera, Attilio Gianpietro
dc.date.accessioned2024-12-30T15:25:55Z
dc.date.available2024-12-30T15:25:55Z
dc.date.issued2024
dc.date.updated2024-12-22T01:04:47Z
dc.description.abstractBackground Type 2 diabetes (T2D) has become a worldwide pandemic. While ceramides may serve as intermediary between obesity-related lipotoxicity and T2D, the relationship with simple glycosphingolipids remains uncertain. The aim of this study was to characterize the associations between blood glycosphingolipid and ceramide species with T2D and to identify a circulating sphingolipid profile that could serve as novel biomarker for T2D risk. Methods Cross-sectional relationship between sphingolipid levels, insulin resistance, and T2D prevalence were evaluated in 2,072 American adults from MIDUS cohort. Prospectively, the association between sphingolipid species and the incidence of T2D was analyzed using a case-cohort design nested within the PREDIMED trial (250 cases and a random sample of 692 participants, with 3.8 years of median follow-up). Circulating levels of sphingolipid species in both populations were measured using LC/MS. Hazard ratios were estimated with weighted Cox regression models using Barlow weights. Results In American adults, only CER18:0 and CER22:0 were linked to insulin resistance and a higher prevalence of T2D. Conversely, three lactosylceramides (LCER 14:0, 16:0, and 24:1) showed a strong inverse relationship with both insulin resistance and T2D. These findings led to development of two sphingolipid scores. In the prospective analysis, these scores consistently predicted a reduced risk of T2D incidence in PREDIMED (HR: 0.64, 95% CI 0.44 to 0.94 and 0.58, 0.40 to 0.85 respectively) between extreme quartiles, with 5-year absolute risk differences of 9.6% (95% CI: 0.3–20.5%) and 11.4% (1.0–21.6%). They were validated in the same trial with samples obtained after 1 year of follow-up. Conclusions Our findings support the potential usefulness of circulating sphingolipid profiles as novel biomarkers for T2D risk. Moreover, this study opens the door for future research on the predictive value and possible protective roles of lactosylceramides in T2D. Graphical abstract
dc.format.extent13 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationCardiovascular Diabetology. 2024 Dec 18;23(1):446
dc.identifier.doi10.1186/s12933-024-02505-7
dc.identifier.urihttps://doi.org/10.1186/s12933-024-02505-7
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/89367
dc.information.autorucEscuela de Medicina; Berkowitz Fiebich, Loni; S/I; 172010
dc.information.autorucEscuela de Medicina; Salazar Vilches, Cristian Javier; S/I; 1089229
dc.information.autorucEscuela de Medicina; Biancardi Roman, Fiorella Carinna; S/I; 1135583
dc.information.autorucEscuela de Medicina; Rigotti Rivera, Attilio Gianpietro; 0000-0002-0495-3525; 68489
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherSpringer Nature
dc.revistaCardiovascular Diabetology
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseCC BY Atribución Internacional 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectType 2 diabetes
dc.subjectSphingolipids
dc.subjectCeramides
dc.subjectLactosylceramides
dc.subjectInsulin resistance
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.ods03 Good Health and Well Being
dc.subject.odspa03 Salud y Bienestar
dc.titleSphingolipid profiling as a biomarker of type 2 diabetes risk: evidence from the MIDUS and PREDIMED studies
dc.typeartículo
sipa.codpersvinculados172010
sipa.codpersvinculados1089229
sipa.codpersvinculados1135583
sipa.codpersvinculados68489
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