{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:57:20Z","timestamp":1792173440342,"version":"4.4.0"},"reference-count":54,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"2","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,1,10]]},"abstract":"<jats:p>\n            Gestational diabetes mellitus (GDM), a transient form of diabetes that resolves postpartum, is a major risk factor for type 2 diabetes (T2D) in women. While the progression from GDM to T2D is not fully understood, it involves both genetic and environmental components. By integrating clinical, metabolomic, and genome-wide association study (GWAS) data, we identified associations between decreased sphingolipid biosynthesis and future T2D, in part through the\n            <jats:italic>rs267738<\/jats:italic>\n            allele of the\n            <jats:italic>CERS2<\/jats:italic>\n            gene in Hispanic women shortly after a GDM pregnancy. To understand the impact of the\n            <jats:italic>CERS2<\/jats:italic>\n            gene and risk allele on glucose regulation, we examined whole-body\n            <jats:italic>Cers2<\/jats:italic>\n            knockout and\n            <jats:italic>rs267738<\/jats:italic>\n            knock-in mice. Both models exhibited glucose intolerance and impaired insulin secretion in vivo. Islets isolated from these models also demonstrated reduced \u03b2 cell function, as shown by decreased insulin secretion ex vivo. Overall, reduced circulating sphingolipids may indicate a high risk of GDM-to-T2D progression and reflect deficits in\n            <jats:italic>CERS2<\/jats:italic>\n            activity that negatively affect glucose homeostasis and \u03b2 cell function.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adr1725","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T18:58:24Z","timestamp":1736535504000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["Reduced circulating sphingolipids and\n            <i>CERS2<\/i>\n            activity are linked to T2D risk and impaired insulin secretion"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-1695","authenticated-orcid":true,"given":"Saifur R.","family":"Khan","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA."},{"name":"VA Medical Center, Pittsburgh, PA, USA."},{"name":"Center for Immunometabolism, University of Pittsburgh, Pittsburgh, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2293-6888","authenticated-orcid":true,"given":"Wenyue W.","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Toronto, Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-7736","authenticated-orcid":true,"given":"Julie A. 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