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. 2022 Aug 18;20(1):374.
doi: 10.1186/s12967-022-03581-7.

Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study

Shu-Yi Li  1 , Si Chen  1 , Xiao-Ting Lu  1 , Ai-Ping Fang  1   2 , Yu-Ming Chen  3 , Rong-Zhu Huang  1 , Xin-Lei Lin  1 , Zi-Hui Huang  1 , Jing-Fei Ma  1 , Bi-Xia Huang  4 , Hui-Lian Zhu  5   6
Affiliations

Serum trimethylamine-N-oxide is associated with incident type 2 diabetes in middle-aged and older adults: a prospective cohort study

Shu-Yi Li et al. J Transl Med. .

Abstract

Background: The role of trimethylamine-N-oxide (TMAO) in the development of diabetes remains controversial, and prospective data are few. We aimed to investigate the association between serum TMAO and incident type 2 diabetes in middle-aged and older adults.

Methods: This study was based on the Guangzhou Nutrition and Health Study (GNHS), a community-based prospective cohort study in China. A total of 2088 diabetes-free participants aged 40-75 years were included from 2008 to 2010. Incident type 2 diabetes was ascertained during follow-up visits. Baseline serum TMAO was measured by high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes across tertiles of serum TMAO were calculated using Cox proportional hazard models. Prospective associations of serum TMAO with changes in glycemic traits (fasting glucose, HbA1c, insulin, HOMA-IR) over time were estimated using linear mixed-effects models (LMEMs).

Results: We ascertained 254 incident type 2 diabetes cases during a median follow-up of 8.9 years. The median (interquartile range) of serum TMAO was 1.54 (0.86-2.91) μmol/L. From the first to the third tertile of serum TMAO, the multivariable-adjusted HRs for diabetes were 1.00 (reference), 1.17 (95% CI: 0.84-1.61), and 1.42 (95% CI: 1.03-1.96) (P-trend = 0.031). LMEMs showed that the estimated yearly change in fasting glucose was 0.011 (0.001-0.022) mmol/L/y in the highest tertile of serum TMAO, compared with the lowest tertile (P-interaction = 0.044). Serum TMAO was not associated with longitudinal changes in HbA1c, insulin or HOMA-IR.

Conclusions: Our findings suggested that higher serum TMAO was associated with a higher risk of type 2 diabetes and an increase in fasting glucose among middle-aged and older Chinese adults.

Trial registration: NCT03179657. https://clinicaltrials.gov/ct2/show/NCT03179657?term=NCT03179657&draw=2&rank=1.

Keywords: Metabolites; Middle-aged and older adults; Prospective cohort; Trimethylamine-N-oxide; Type 2 diabetes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Stratified HRs and 95% CIs of type 2 diabetes according to tertiles (T) of serum TMAOa. TMAO trimethylamine-N-oxide, HR hazard ratio, 95% CI 95% confidence interval, T tertile. aIn multivariable-adjusted model, confounding factors included age, sex, household income, smoking status, alcohol drinking, tea drinking, hypertension, WHR, physical activity, intakes of total energy, egg, red and processed meat, fish and shellfish, serum levels of TG, HDL-C and fasting glucose. The medians of age, serum fasting glucose, serum choline, serum betaine, red and processed meat intake, fish and shellfish intake, or egg intake were cut-off points
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