TMAO and diabetes: from the gut feeling to the heart of the problem

Abstract Elevated plasma levels of trimethylamine N-oxide (TMAO)—a compound derived from diet and the gut microbiome—have been widely studied for their association with diabetes risk and their potential role in disease pathophysiology and complications. However, clinical studies, both prospective an...

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Main Authors: Kinga Jaworska, Monika Kuś, Marcin Ufnal
Format: Article
Language:English
Published: Nature Publishing Group 2025-05-01
Series:Nutrition & Diabetes
Online Access:https://doi.org/10.1038/s41387-025-00377-8
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author Kinga Jaworska
Monika Kuś
Marcin Ufnal
author_facet Kinga Jaworska
Monika Kuś
Marcin Ufnal
author_sort Kinga Jaworska
collection DOAJ
description Abstract Elevated plasma levels of trimethylamine N-oxide (TMAO)—a compound derived from diet and the gut microbiome—have been widely studied for their association with diabetes risk and their potential role in disease pathophysiology and complications. However, clinical studies, both prospective and retrospective, have yielded conflicting results. For example, elevated levels of TMAO are frequently linked to an increased risk of cardiovascular and renal complications in individuals with diabetes. However, the robustness and independence of these associations differ across study populations and are influenced by the degree of adjustment for confounding risk factors. Considering insulin’s regulatory effect on FMO3 activity in liver cells, TMAO may serve as a marker of hepatic insulin resistance, which could partially explain its association with diabetes risk. The role of TMAO in diabetes pathology remains controversial; while some studies emphasize its detrimental impact on insulin sensitivity and the progression of diabetes-related complications, others suggest potential protective effects. Investigating the largely unexplored role of TMAO’s precursor, trimethylamine, may help elucidate these discrepancies. This review consolidates clinical and experimental findings to clarify TMAO’s complex mechanistic contributions to diabetes pathology.
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spelling doaj-art-77d9928a62d14f2a87eeaaa37f2c1e882025-08-20T03:54:11ZengNature Publishing GroupNutrition & Diabetes2044-40522025-05-0115111210.1038/s41387-025-00377-8TMAO and diabetes: from the gut feeling to the heart of the problemKinga Jaworska0Monika Kuś1Marcin Ufnal2Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of WarsawDepartment of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of WarsawDepartment of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of WarsawAbstract Elevated plasma levels of trimethylamine N-oxide (TMAO)—a compound derived from diet and the gut microbiome—have been widely studied for their association with diabetes risk and their potential role in disease pathophysiology and complications. However, clinical studies, both prospective and retrospective, have yielded conflicting results. For example, elevated levels of TMAO are frequently linked to an increased risk of cardiovascular and renal complications in individuals with diabetes. However, the robustness and independence of these associations differ across study populations and are influenced by the degree of adjustment for confounding risk factors. Considering insulin’s regulatory effect on FMO3 activity in liver cells, TMAO may serve as a marker of hepatic insulin resistance, which could partially explain its association with diabetes risk. The role of TMAO in diabetes pathology remains controversial; while some studies emphasize its detrimental impact on insulin sensitivity and the progression of diabetes-related complications, others suggest potential protective effects. Investigating the largely unexplored role of TMAO’s precursor, trimethylamine, may help elucidate these discrepancies. This review consolidates clinical and experimental findings to clarify TMAO’s complex mechanistic contributions to diabetes pathology.https://doi.org/10.1038/s41387-025-00377-8
spellingShingle Kinga Jaworska
Monika Kuś
Marcin Ufnal
TMAO and diabetes: from the gut feeling to the heart of the problem
Nutrition & Diabetes
title TMAO and diabetes: from the gut feeling to the heart of the problem
title_full TMAO and diabetes: from the gut feeling to the heart of the problem
title_fullStr TMAO and diabetes: from the gut feeling to the heart of the problem
title_full_unstemmed TMAO and diabetes: from the gut feeling to the heart of the problem
title_short TMAO and diabetes: from the gut feeling to the heart of the problem
title_sort tmao and diabetes from the gut feeling to the heart of the problem
url https://doi.org/10.1038/s41387-025-00377-8
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