Journal of Translational Medicine (Aug 2022)

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

  • Shu-yi Li,
  • Si Chen,
  • Xiao-ting Lu,
  • Ai-ping Fang,
  • Yu-ming Chen,
  • Rong-zhu Huang,
  • Xin-lei Lin,
  • Zi-hui Huang,
  • Jing-fei Ma,
  • Bi-xia Huang,
  • Hui-lian Zhu

DOI
https://doi.org/10.1186/s12967-022-03581-7
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 10

Abstract

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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

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