Oral glucose absorption is enhanced in early metabolic dysfunction-associated steatotic liver disease
Date
2026
Authors
Tricò, D.
Wu, T.
Cimbalo, N.
Chiriacò, M.
Xie, C.
Sacchetta, L.
Nesti, L.
Gallo, S.
Santoni, L.
Masoni, M.C.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Diabetologia, 2026; 1-15
Statement of Responsibility
Domenico Tricò, Tongzhi Wu, Noemi Cimbalo, Martina Chiriacò, Cong Xie, Luca Sacchetta, Lorenzo Nesti, Simone Gallo, Lorenza Santoni, Maria C. Masoni, Giovanni Petralli, Teresa V. Fiorentino, Roberto Bizzotto, Maria T. Scozzaro, Silvia Frascerra, Simona Baldi, Maurizia R. Brunetto, Andrea Mari, Christopher K. Rayner, Andrea Natali
Conference Name
Abstract
Aims/hypothesis: Hepatic glucose flux plays a crucial role in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), promoting de novo lipogenesis, inflammation and fibrosis. 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. Methods: 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 13C-acetate breath test during an OGTT and estimated hepatic steatosis risk. Results: 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±142 μmol/kg, p=0.031), resulting in a 52% increase in total glucose absorption (+6.4±1.8 g, p=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], p=0.036), independent of potential confounders. Gastric emptying rate was not associated with hepatic steatosis risk. Conclusions/interpretation: 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.
School/Discipline
Dissertation Note
Provenance
Description
OnlinePubl
Access Status
Rights
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.