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This study aimed to evaluate the kinetics of oral glucose absorption and one of its key modulators, gastric emptying, in individuals with early-stage MASLD vs matched control individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We quantified glucose metabolic fluxes during a 75 g OGTT using stable isotopes in individuals with MASLD without fibrosis and in healthy control individuals. In a separate cohort, we measured the gastric emptying rate using the\n                      <jats:sup>13<\/jats:sup>\n                      C-acetate breath test during an OGTT and estimated hepatic steatosis risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the control group, in the MASLD group the rate of appearance of oral ingested glucose (RaO) normalised to body weight was 34% higher at 1 h post-OGTT (+318\u00b1142 \u00b5mol\/kg,\n                      <jats:italic>p<\/jats:italic>\n                      =0.031), resulting in a 52% increase in total glucose absorption (+6.4\u00b11.8 g,\n                      <jats:italic>p<\/jats:italic>\n                      =0.001). Participants with MASLD exhibited reduced glucose clearance relative to plasma insulin levels but preserved post-load suppression of endogenous glucose production, indicating peripheral rather than hepatic insulin resistance. Among glucose metabolic fluxes, RaO showed the strongest association with prevalent MASLD, with each 1-SD increase in 1 h RaO being associated with fivefold higher odds of MASLD (OR 4.99 [95% CI 1.44, 31.57],\n                      <jats:italic>p<\/jats:italic>\n                      =0.036), independent of potential confounders. Gastric emptying rate was not associated with hepatic steatosis risk.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Oral glucose absorption is augmented in individuals with MASLD without fibrosis, apparently unrelated to accelerated gastric emptying. This metabolic alteration may represent an early driver of MASLD pathogenesis, preceding hepatic insulin resistance. Future research should investigate whether modulation of intestinal glucose absorption confers therapeutic benefits in MASLD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06730-5","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T12:33:54Z","timestamp":1776774834000},"page":"2073-2087","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral glucose absorption is enhanced in early metabolic dysfunction-associated steatotic liver 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We also thank A. Mengozzi and G. Nesti at the University of Pisa (Pisa, Italy), M. Borg and Y. Sun at the University of Adelaide (Adelaide, Australia), and all clinical staff, nurses and research coordinators at the two institutions for their assistance with participant recruitment, data collection and study implementation. Preliminary findings from this study were previously presented at the EASD Annual Meeting, held in Vienna, Austria, in September 2025, and the Italian Society of Internal Medicine (SIMI) Annual Meeting, held in Rimini, Italy, in October 2025. The current manuscript provides a comprehensive and updated analysis of the full dataset, incorporating additional results and extended discussion not included in the earlier presentations.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"The data that support the study findings are available from the corresponding authors on reasonable request starting from the date of publication and will remain accessible for a minimum of 10 years, in line with institutional policies. Access will be granted to qualified researchers to address research questions that are consistent with the scope of the original study and meet ethical and legal requirements.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"Open Access funding enabled and organized by CAUL and its Member Institutions. We acknowledge financial support under the National Recovery and Resilience Plan (PNRR), Mission 4, Component 2, Investment 1.1, Call for tender no. 104 published on 2 February 2022 by the Italian Ministry of University and Research (MUR), funded by the European Union \u2013 NextGenerationEU \u2013 Project Title \u2018Exploring the role of SGLT-1 driven intestinal glucose absorption and altered intestinal mucosa integrity in the pathogenesis of non-alcoholic fatty liver disease\u2019 \u2013 CUP I53D23005180001, F53D23007130006 and B53D23021760006 \u2013 grant assignment decree no. 2022LWXFM4 dated 20 July 2023. Data obtained at the University of Adelaide were funded by an Australian National Health and Medical Research Council (NHMRC) Ideas Grant awarded to CKR (ID 2020454). CX has been supported by an Australian Diabetes Society Skip-Martin Early Career Fellowship. TW has been supported by the Australian Medical Research Future Fund (MRFF) (ID: MRFCDDM000009). CKR is supported by the Michell Bequest Foundation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"The study was conceived by DT and designed by DT, TW, AM, CKR and AN. Funding was obtained by DT, TW, TVF, RB, CKR and AN. All authors contributed to the acquisition, analysis or interpretation of the data. Statistical analysis and mathematical modelling were performed by DT, CX and AM. DT drafted the manuscript, and all authors critically revised it for important intellectual content. CKR and AN supervised the work. All authors approved the final version of the manuscript. DT and AN take responsibility for the integrity of the work as a whole.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}