(17-09-2017) Association between microbiota-dependent metabolite trimethylamine-N-oxide and type 2 diabetes

Zhilei Shan1–3, Taoping Sun1,2, Hao Huang1,2, Sijing Chen1,2, Liangkai Chen1,2, Cheng Luo1,2, Wei Yang1,2, Xuefeng Yang1,2, Ping Yao1,2, Jinquan Cheng5, Frank B Hu3,4, and Liegang Liu1,2
+Author Affiliations

1Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, and
2Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;
3Departments of Nutrition and
4Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; and
5Shenzhen Center for Disease Control and Prevention, Shenzhen, China
+Author Notes

Abstract
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 μmol/L (0.81–2.20 μmol/L) for controls and 1.77 μmol/L (1.09–2.80 μmol/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) (P-trend < 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.

Source: Am J Clin Nutr September 2017
vol. 106 no. 3 888-894

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