Jaworska Kinga, Kuś Monika, Ufnal Marcin
Department of Experimental Physiology and Pathophysiology, Laboratory of the Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Nutr Diabetes. 2025 May 20;15(1):21. doi: 10.1038/s41387-025-00377-8.
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.
三甲胺 N-氧化物（TMAO）是一种源自饮食和肠道微生物群的化合物，其血浆水平升高与糖尿病风险的关联以及在疾病病理生理学和并发症中的潜在作用已得到广泛研究。然而，前瞻性和回顾性的临床研究都得出了相互矛盾的结果。例如，TMAO 水平升高通常与糖尿病患者心血管和肾脏并发症风险增加有关。然而，这些关联的稳健性和独立性在不同研究人群中有所不同，并受到混杂风险因素调整程度的影响。考虑到胰岛素对肝细胞中 FMO3 活性的调节作用，TMAO 可能作为肝脏胰岛素抵抗的标志物，这可以部分解释其与糖尿病风险的关联。TMAO 在糖尿病病理中的作用仍存在争议；虽然一些研究强调其对胰岛素敏感性和糖尿病相关并发症进展的有害影响，但其他研究则提出了潜在的保护作用。研究 TMAO 的前体三甲胺在很大程度上未被探索的作用，可能有助于阐明这些差异。本综述整合了临床和实验结果，以阐明 TMAO 对糖尿病病理的复杂机制贡献。
