{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:06:50Z","timestamp":1789103210500,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gestational diabetes mellitus (GDM) is particularly prevalent in twin pregnancies, yet the underlying metabolic pathways remain incompletely elucidated. Remnant cholesterol (RC), derived from standard lipid measurements, has been associated with glucose metabolic disorders, but its association with GDM in twin pregnancies is unknown. Whether chorionicity modifies this association has not been investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included 347 women with twin pregnancies who delivered at a tertiary hospital in China between 2020 and 2025. First-trimester calculated RC was derived as total cholesterol minus LDL-C and HDL-C. Its association with GDM was examined using multivariable logistic regression and restricted cubic splines. Potential effect modification by chorionicity was evaluated using interaction analysis. As a secondary exploratory analysis, the stand-alone discrimination of calculated RC was assessed using ROC curve analysis, and a data-derived cut-off was identified using the Youden index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After adjustment for age, education, pre-pregnancy body mass index, assisted reproductive technology, gravidity, primiparous status, and chorionicity, calculated RC was associated with GDM (\n                      <jats:italic>P<\/jats:italic>\n                      for overall=0.024), with no evidence of non-linearity (\n                      <jats:italic>P<\/jats:italic>\n                      = 0.673). The internally derived exploratory cut-off was 1.145 mmol\/L, with an AUC of 0.649 (95% CI 0.572\u20130.724), specificity of 44.95%, and positive predictive value of 22.93%. Calculated RC \u22651.145 mmol\/L was associated with higher odds of GDM (adjusted OR 2.56, 95% CI 1.28\u20135.10;\n                      <jats:italic>P<\/jats:italic>\n                      = 0.008). An exploratory interaction by chorionicity was observed (\n                      <jats:italic>P<\/jats:italic>\n                      for interaction=0.024), but the monochorionic subgroup contained only 10 GDM events and the estimate was imprecise.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated first-trimester calculated RC was associated with subsequent GDM in women with twin pregnancies. The 1.145 mmol\/L cut-off was exploratory and internally derived and requires external validation, whereas the potential heterogeneity by chorionicity should be regarded as hypothesis-generating and further explored in larger prospective cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1882821","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:30:28Z","timestamp":1789101028000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["First-trimester calculated remnant cholesterol and gestational diabetes mellitus in twin pregnancies: a retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Kejun","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University","place":["Ruian, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, Zhejiang University","place":["Hangzhou, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University","place":["Ruian, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruru","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University","place":["Ruian, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yingjie","sequence":"additional","affiliation":[{"name":"Department of Emergency, Shishi Municipal Hospital","place":["Quanzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjia","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Laboratory for the Diagnosis and Prevention of Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University","place":["Ruian, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","article-title":"IDF Diabetes Atlas","year":"2015"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1056\/NEJMoa0707943","article-title":"Hyperglycemia and adverse pregnancy outcomes","volume":"358","author":"Metzger","year":"2008","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60731-5","article-title":"Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis","volume":"373","author":"Bellamy","year":"2009","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/j.1467-789X.2008.00541.x","article-title":"Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis","volume":"10","author":"Torloni","year":"2009","journal-title":"Obes Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2019.1670790","article-title":"Risk of gestational diabetes mellitus following assisted reproductive technology: systematic review and meta-analysis of 59 cohort studies","volume":"34","author":"Maroufizadeh","year":"2021","journal-title":"J Matern Fetal Neonatal Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-018-4847-9","article-title":"Incidence and risk factors for gestational diabetes mellitus in twin versus singleton pregnancies","volume":"298","author":"Hiersch","year":"2018","journal-title":"Arch Gynecol Obstet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2024.01.004","article-title":"Gestational diabetes in twin pregnancies-a pathology requiring treatment or a benign physiological adaptation","volume":"231","author":"Melamed","year":"2024","journal-title":"Am J Obstet Gynecol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2013.11.008","article-title":"Remnant cholesterol as a cause of ischemic heart disease: evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment","volume":"141","author":"Varbo","year":"2014","journal-title":"Pharmacol Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2023.102215","article-title":"Cumulative remnant cholesterol as a causal risk factor for ischemic heart disease: A prospective cohort study","volume":"49","author":"Zhao","year":"2024","journal-title":"Curr Probl Cardiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2451","DOI":"10.1038\/s41467-024-46686-x","article-title":"Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity","volume":"15","author":"Zhao","year":"2024","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/978-3-031-63657-8_17","article-title":"Endothelial dysfunction in obesity and therapeutic targets","volume":"1460","author":"Engin","year":"2024","journal-title":"Adv Exp Med Biol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1186\/s12967-023-04322-0","article-title":"Remnant cholesterol, but not other cholesterol parameters, is associated with gestational diabetes mellitus in pregnant women: a prospective cohort study","volume":"21","author":"Gao","year":"2023","journal-title":"J Transl Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/jim-2022-002412","article-title":"Analysis of the characteristics of blood lipid metabolism in twin pregnancy","volume":"71","author":"Lou","year":"2023","journal-title":"J Investig Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.ajog.2012.09.025","article-title":"The vascular anastomoses in monochorionic twin pregnancies and their clinical consequences","volume":"208","author":"Lewi","year":"2013","journal-title":"Am J Obstet Gynecol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1186\/s12884-021-03744-2","article-title":"Placental glucose transporter 1 and 3 gene expression in Monochorionic twin pregnancies with selective fetal growth restriction","volume":"21","author":"Chang","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad262","article-title":"Remnant cholesterol is associated with gestational diabetes mellitus: a cohort study","volume":"108","author":"Wang","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-1848","article-title":"International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.10.012","article-title":"Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: a World Health Organization Guideline","volume":"103","author":"Agarwal","year":"2014","journal-title":"Diabetes Res Clin Pract"},{"key":"B19","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.preghy.2018.05.004","article-title":"The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice","volume":"13","author":"Brown","year":"2018","journal-title":"Pregnancy Hypertens"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003891","article-title":"Gestational hypertension and preeclampsia: ACOG practice bulletin, number 222","volume":"135","year":"2020","journal-title":"Obstet Gynecol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1097\/AOG.0000000000004142","article-title":"ACOG practice bulletin No. 217: Prelabor rupture of membranes","volume":"136","author":"Siegler","year":"2020","journal-title":"Obstet Gynecol"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-19425-7","article-title":"Regression Modeling Strategies: With Applications to Linear Models, Logistic and Ordinal Regression, and Survival Analysis","author":"Harrell","year":"2015"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.15.04172","article-title":"The mediating role of inflammation-related indicators in the association of remnant cholesterol with gestational diabetes mellitus","volume":"15","author":"Lin","year":"2025","journal-title":"J Glob Health"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0258(19980430)17:8<857::aid-sim777>3.0.co;2-e","article-title":"Two-sided confidence intervals for the single proportion: comparison of seven methods","volume":"17","author":"Newcombe","year":"1998","journal-title":"Stat Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s12944-024-02230-w","article-title":"Associations of remnant cholesterol in early pregnancy with gestational diabetes mellitus risk: a prospective birth cohort study","volume":"23","author":"Su","year":"2024","journal-title":"Lipids Health Dis"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.02.004","article-title":"Imbalanced insulin action in chronic over nutrition: Clinical harm, molecular mechanisms, and a way forward","volume":"247","author":"Williams","year":"2016","journal-title":"Atherosclerosis"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8171989","article-title":"Palmitic acid induces microRNA-221 expression to decrease glucose uptake in HepG2 cells via the PI3K\/AKT\/GLUT4 pathway","volume":"2019","author":"Huang","year":"2019","journal-title":"BioMed Res Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2012.06.011","article-title":"Biochemical basis and clinical consequences of glucolipotoxicity: a primer","volume":"8","author":"Srinivasan","year":"2012","journal-title":"Heart Fail Clin"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.04.012","article-title":"Cholesterol metabolism, pancreatic beta-cell function and diabetes","volume":"1865","author":"Perego","year":"2019","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3467","DOI":"10.3390\/ijms19113467","article-title":"Maternal beta-cell adaptations in pregnancy and placental signalling: Implications for gestational diabetes","volume":"19","author":"Moyce","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2840-13-71","article-title":"Bezafibrate improves postprandial hypertriglyceridemia and associated endothelial dysfunction in patients with metabolic syndrome: a randomized crossover study","volume":"13","author":"Ohno","year":"2014","journal-title":"Cardiovasc Diabetol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00010.2016","article-title":"Endothelial transcytosis of insulin: Does it contribute to insulin resistance","volume":"31","author":"Lee","year":"2016","journal-title":"Physiol (Bethesda)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1882821\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:30:53Z","timestamp":1789101053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1882821\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":32,"alternative-id":["10.3389\/fendo.2026.1882821"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1882821","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1882821"}}