Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

作者:Shan, Zhilei; Sun, Taoping; Huang, Hao; Chen, Sijing; Chen, Liangkai; Luo, Cheng; Yang, Wei; Yang, Xuefeng; Yao, Ping; Cheng, Jinquan; Hu, Frank B.*; Liu, Liegang*
来源:American Journal of Clinical Nutrition, 2017, 106(3): 888-894.
DOI:10.3945/ajcn.117.157107

摘要

Background: The association of trimethylamine-N-oxide (TMAO), a microbiota-dependent metabolite from dietary choline and carnitine, with type 2 diabetes was inconsistent. @@@ Objective: We evaluated the association of plasma TMAO with newly diagnosed type 2 diabetes and the potential modification of TMAO-generating enzyme flavin monooxygenase 3 (FMO3) polymorphisms. @@@ Design: This was an age-and sex-matched case-control study of 2694 participants: 1346 newly diagnosed cases of type 2 diabetes and 1348 controls. Concentrations of plasma TMAO were measured, and FMO3 E158K polymorphisms (rs2266782) were genotyped. @@@ Results: Medians (IQRs) of plasma TMAO concentration were 1.47 mu mol/L (0.81-2.20 mu mol/L) for controls and 1.77 mu mol/L (1.09-2.80 mu mol/L) for type 2 diabetes cases. From the lowest to the highest quartiles of plasma TMAO, the multivariable adjusted ORs of type 2 diabetes were 1.00 (reference), 1.38 (95% CI: 1.08, 1.77), 1.64 (95% CI: 1.28, 2.09), and 2.55 (95% CI: 1.99, 3.28) (Ptrend, 0.001); each SD of ln-transformed plasma TMAO was associated with a 38% (95% CI: 26%, 51%) increment in ORs of type 2 diabetes. The FMO3 rs2266782 polymorphism was not associated with type 2 diabetes. The positive association between plasma TMAO and type 2 diabetes was consistent in each rs2266782 genotype group, and no significant interaction was observed (P = 0.093). @@@ Conclusions: Our results suggested that higher plasma TMAO was associated with increased odds of newly diagnosed type 2 diabetes and that this association was not modified by the FMO3 rs2266782 polymorphism. This study was registered at clinicaltrials. gov as NCT03130894.