Abstract
BACKGROUND: Trimethylamine N-oxide (TMAO) and its precursors have an association with type 2 diabetes mellitus (T2DM); however, the evidence is unclear. The current study examined the association of serial measures of serum TMAO and related metabolite concentrations with the risk of T2DM. METHODS: Our study was designed as a community case-control study with 300 participants (150 T2DM and 150 non-T2DM). We examined the association of serum concentrations of TMAO and its related metabolites [trimethylamine, choline, betaine, and L-carnitine] using UPLC-MS/MS. The association between these metabolites and the risk of T2DM was analyzed using a restricted cubic spline and binary logistic regression. RESULTS: A higher serum choline concentration was significantly associated with an increased risk of T2DM. Serum choline > 22.62 μmol/L was independently associated with an increased risk of T2DM, and the odds ratio was 3.615 [95% CI: (1.453,8.993), P = 0.006]. Similarly, serum betaine and L-carnitine concentrations had a markedly decreased risk of T2DM even after adjusting for the traditional risk factors for T2DM and betaine (0.978 [95% CI:0.964-0.992], P = 0.002) and L-carnitine (0.949 [95% CI: 0.9222-0.978], P = 0.001), respectively. CONCLUSION: Choline, betaine, and L-carnitine are associated with the risk of T2DM and may be appropriate risk markers to protect high-risk individuals from T2DM.