@article{41b8cafd7d6943e595078fc7cf592df3,
title = "Insights into circulating CEACAM1 in insulin clearance and disease progression: Evidence from the Portuguese PREVADIAB2 study",
abstract = "Background: Type 2 diabetes (T2DM) and obesity are characterized by altered insulin metabolism and action. 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. Methods: A total of 1019 individuals from the PREVADIAB2 cohort were evaluated for diabetes by 75 g-OGTT 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–Wallis and Wilcoxon–Mann–Whitney tests. Results: BMI, insulin resistance (HOMA-IR), 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. Conclusions: 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.",
keywords = "CEACAM1, diabetes, hepatic steatosis, hyperinsulinemia, insulin clearance, insulin resistance",
author = "Patarr{\~a}o, {Rita S.} and Meneses, {Maria Jo{\~a}o} and Ghadieh, {Hilda E.} and Laura Herrera and S{\'e}rgio Duarte and Ribeiro, {Rog{\'e}rio T.} and Raposo, {Jo{\~a}o F.} and Verena Schmitt and Singer, {Bernhard B.} and Amalia Gastaldelli and Carlos Penha-Gon{\c c}alves and Najjar, {Sonia M.} and Macedo, {M. Paula}",
note = "Funding Information: The authors thank the study participants for commitment and loyalty. The authors would like to acknowledge the guidance of the late PD Dr. Bernhard B. Singer, PhD and from Verena Schmitt, PhD from the Universit\u00E4tsklinikum, Essen, Germany for their guidance on setting up the ELISA analysis of circulating CEACAM1 levels. This study was supported by \u201CFunda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia\u201D \u2013 iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission, Horizon Europe Framework Programme, PAS GRAS (Grant agreement n. 101080329) and by the Sociedade Portuguesa de Diabetologia. The study was also partly supported by grants from the US National Institutes of Health [R01-DK054254 and R01-MD012579] and from the Osteopathic Heritage Foundation J.J. Kopchick, PhD, Endowed Eminent Research Chair to SMN. Funding Information: The authors thank the study participants for commitment and loyalty. The authors would like to acknowledge the guidance of the late PD Dr. Bernhard B. Singer, PhD and from Verena Schmitt, PhD from the Universit\u00E4tsklinikum, Essen, Germany for their guidance on setting up the ELISA analysis of circulating CEACAM1 levels. This study was supported by \u201CFunda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia\u201D \u2013 iNOVA4Health (UIDB/Multi/04462/2020), by the European Commission, Horizon Europe Framework Programme, PAS GRAS (Grant agreement n. 101080329) and by the Sociedade Portuguesa de Diabetologia. The study was also partly supported by grants from the US National Institutes of Health [R01\u2010DK054254 and R01\u2010MD012579] and from the Osteopathic Heritage Foundation J.J. Kopchick, PhD, Endowed Eminent Research Chair to SMN. Publisher Copyright: {\textcopyright} 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.",
year = "2024",
month = dec,
doi = "10.1111/eci.14344",
language = "English",
volume = "54",
journal = "European Journal Of Clinical Investigation",
issn = "0014-2972",
publisher = "Blackwell Publishing Ltd",
number = "S2",
}
