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Reduced hepatic insulin clearance is increasingly recognized as a key contributor to hyperinsulinemia and insulin resistance. CEACAM1 promotes hepatic insulin clearance, and its loss in hepatocytes is associated with reduced insulin clearance in mice and men. This study examines whether CEACAM1 circulating levels reflect compromised insulin metabolism and resistance in the PREVADIAB2 cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 1019 individuals from the PREVADIAB2 cohort were evaluated for diabetes by 75\u2009g\u2010OGTT and classified according to WHO 2019 criteria. CEACAM1 circulating levels were measured by ELISA, and insulin metabolism parameters were calculated. Hierarchical clustering of insulin metabolic indices and CEACAM1 levels was performed. Statistical significance was assessed using Kruskal\u2013Wallis and Wilcoxon\u2013Mann\u2013Whitney tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BMI, insulin resistance (HOMA\u2010IR), and hepatic steatosis progressively increased with disease severity. Insulin secretion rose and its clearance declined in parallel to circulating CEACAM1 levels in prediabetes and T2DM, indicating compensatory hyperinsulinemia. Hierarchical metabolic clustering identified four clusters with distinct patterns and further showed that insulin clearance positively correlated with circulating CEACAM1, especially in individuals with normoglycemia, lower obesity and hepatic steatosis. This suggests that circulating CEACAM1 can reflect the status of hepatic insulin clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates a progressive increase in insulin resistance and hyperinsulinemia in parallel to elevated BMI and hepatic steatosis prevalence, accompanied by declining circulating CEACAM1 levels. Cluster analysis further linked reduced insulin clearance to lower circulating CEACAM1 levels, suggesting its potential usefulness as a biomarker for metabolic disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.14344","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T05:01:22Z","timestamp":1734238882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study"],"prefix":"10.1111","volume":"54","author":[{"given":"Rita S.","family":"Patarr\u00e3o","sequence":"first","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM Universidade NOVA de Lisboa  Lisbon Portugal"}]},{"given":"Maria Jo\u00e3o","family":"Meneses","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM Universidade NOVA de Lisboa  Lisbon Portugal"}]},{"given":"Hilda E.","family":"Ghadieh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"},{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences University of Balamand  Al\u2010Koura Lebanon"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2899-4988","authenticated-orcid":false,"given":"Laura","family":"Herrera","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM Universidade NOVA de Lisboa  Lisbon Portugal"},{"name":"APDP \u2013 Diabetes Portugal Education and Research Center  Lisbon Portugal"}]},{"given":"S\u00e9rgio","family":"Duarte","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine University of Florida  Gainesville Florida USA"}]},{"given":"Rog\u00e9rio T.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"APDP \u2013 Diabetes Portugal Education and Research Center  Lisbon Portugal"}]},{"given":"Jo\u00e3o F.","family":"Raposo","sequence":"additional","affiliation":[{"name":"iNOVA4Health, NOVA Medical School, Faculdade de Ci\u00eancias M\u00e9dicas, NMS, FCM Universidade NOVA de Lisboa  Lisbon Portugal"},{"name":"APDP \u2013 Diabetes Portugal Education and Research Center  Lisbon Portugal"},{"name":"Portuguese Society of Diabetology  Lisbon Portugal"}]},{"given":"Verena","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Medical Faculty University of Duisburg\u2010Essen  Essen Germany"}]},{"given":"Bernhard B.","family":"Singer","sequence":"additional","affiliation":[{"name":"Institute of Anatomy, Medical Faculty University of Duisburg\u2010Essen  Essen Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2594-1651","authenticated-orcid":false,"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"National Research Council (CNR) Institute of Clinical Physiology (IFC)  Pisa Italy"}]},{"given":"Carlos","family":"Penha\u2010Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"APDP \u2013 Diabetes Portugal Education and Research Center  Lisbon Portugal"}]},{"given":"Sonia M.","family":"Najjar","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"},{"name":"Diabetes Institute, Heritage College of Osteopathic Medicine Ohio University  Athens Ohio USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2549-0275","authenticated-orcid":false,"given":"M. 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