{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:15:34Z","timestamp":1790972134073,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013279","name":"Joint Programming Initiative A healthy diet for a healthy life","doi-asserted-by":"publisher","award":["696295"],"award-info":[{"award-number":["696295"]}],"id":[{"id":"10.13039\/100013279","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009882","name":"Regione Lombardia","doi-asserted-by":"publisher","award":["Decr. RL 13465, 22\/12\/2010"],"award-info":[{"award-number":["Decr. RL 13465, 22\/12\/2010"]}],"id":[{"id":"10.13039\/501100009882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Circulating bile acids (cBAs) function as signaling molecules that activate the farnesoid X receptor (FXR), promoting the secretion of fibroblast growth factor 19 (FGF-19), a gut-derived hormone involved in bile acid (BA) synthesis, glucose metabolism, and insulin sensitivity. However, the relationship between fasting cBAs, FGF-19, and insulin resistance\u2014as estimated by HOMA-IR\u2014remains unclear. This study explored these associations in an elderly population from Northern Italy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>We examined a subsample of 1080 subjects (aged 60\u201375 years, 1:1 male-to-female ratio) from the RoCAV population-based study (2013\u20132016). Fasting blood samples were analyzed for 33 cBAs using UHPLC-MS\/MS, of which 23 met quality criteria. FGF-19 levels were also measured. After excluding individuals with missing data or fibrate therapy, 1049 participants were included. Associations between cBAs, FGF-19, and HOMA-IR were assessed via linear regression, adjusting for age, sex, BMI, diet, alcohol intake, hypertension, and dyslipidemia. ROC curve analysis evaluated the ability of cBAs and FGF-19 to discriminate T2DM cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After excluding participants with missing anthropometric and clinical data or in fibrate treatment, data from 1049 subjects (mean\u00b1SD age 68.6\u00b14.5 years, males 49.5%, T2DM 10.6%) were analysed. FGF-19 showed a positive correlation with primary cBAs (Spearman\u2019s \u03c1=0.33, p&amp;lt;0.001). Adjusted for covariates, both primary and secondary cBAs were positively associated with HOMA-IR (\u03b2=0.07, p=5\u00d710<jats:sup>-5<\/jats:sup>; \u03b2=0.9, p=4\u00d710<jats:sup>-7<\/jats:sup>) while FGF-19 was not (\u03b2=-0.02, p=0.31). In the mutually-adjusted model - including primary and secondary cBAs, FGF-19, and covariates - the \u03b2 coefficients for cBAs were attenuated but remained significant (primary: \u03b2=0.06, p=0.005; secondary: \u03b2=0.07, p=0.0003), and FGF-19 retained an inverse association (\u03b2=\u20130.05, p=0.009). When total cBAs were used in the FGF-19\u2013adjusted model, the association with HOMA-IR was the strongest (\u03b2=0.19, p=5\u00d710<jats:sup>-19<\/jats:sup>). ROC curve analysis indicated that the inclusion of primary and secondary cBAs and FGF-19 improved model discrimination for T2DM (\u0394AUC=0.03, 95% Confidence Interval: 0.01-0.06; Net Reclassification Improvement=0.54; 95%CI: 0.30-0.75).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this elderly Italian population, primary and secondary cBAs were positively associated with insulin resistance, after adjusting for each other, whereas FGF-19 negatively. These markers may enhance T2DM risk stratification and may give insights on bile acid\u2013glucose metabolism links.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1656942","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T04:23:33Z","timestamp":1760502213000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Circulating bile acids and HOMA-IR: cross-sectional results from the RoCAV population-based study"],"prefix":"10.3389","volume":"16","author":[{"given":"Sarah","family":"Grossi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele 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