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. 2025 Jun 16:12:1587863.
doi: 10.3389/fnut.2025.1587863. eCollection 2025.

Associations of first-trimester TMAO and its precursors with gestational diabetes mellitus: a pilot prospective cohort study

Geng-Dong Chen #  1   2   3 , Ting-Ting Pang #  4 , Peng-Sheng Li  1   2   3 , Shao-Xin Ye  1 , Xiao-Yan Gou  1 , Hai-Yan Wang  1 , Dong-Xin Lin  1   2   3 , Da-Zhi Fan  1   2   3 , Lu-Sha Deng  4 , Li-Juan Wang  5 , Zi-Xing Zhou  1   2   3
Affiliations

Associations of first-trimester TMAO and its precursors with gestational diabetes mellitus: a pilot prospective cohort study

Geng-Dong Chen et al. Front Nutr. .

Abstract

Aims: We aimed to provide a comprehensive understanding of the associations between Trimethylamine-N-oxide (TMAO), its precursor and gestational diabetes mellitus (GDM).

Methods: In this prospective study, 940 women were included in a Chinese single -center pregnant cohort. First trimester plasma concentrations of TMAO and its precursors (betaine, choline, L-carnitine, and trimethylamine) were measured using UPLC-ESI-MS/MS. GDM and specific abnormal glucose levels (fasting glucose; one-hour post-load glucose, 1-h PG; two-hour post load glucose, 2-h PG; and 1-h PG ≥ 8.6 mmol/L) were assessed through oral glucose tolerance tests. First-trimester plasma concentrations of TMAO and its precursors were divided into quartile groups (bottom, Q1; middle, Q2 and Q3; top, Q4).

Results: Among the subjects, 167 (17.8%) were found to have GDM. After adjusting for potential covariates, the lower groups (Q1) of L-carnitine were associated with a higher risk of GDM compared to the reference group (middle quartiles). The OR (95% CI, p) was1.56 (1.04, 2.35, p = 0.032) for L-carnitine. Specifically, the associations were mainly derived from L-carnitine and abnormal 1-h PG. The ORs (95% CI, p) were 2.00 (1.24, 3.24, p = 0.005).

Conclusion: Low plasma levels (bottom vs. middle quartiles) of L-carnitine the first-trimester pregnancy were associated with a higher risk of GDM and abnormal 1-h PG in Chinese pregnant women.

Keywords: L-carnitine; TMAO precursors; gestational diabetes mellitus; pregnant women; trimethylamine N-oxide (TMAO).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Associations between TMAO and its precursors and the risk of Gestational diabetes mellitus (GDM). The associations were adjusted for covariates in Model 2, which included age, pre-pregnancy BMI, parity, gravidity, education, family income, and gestational weight gain.
Figure 2
Figure 2
Dose-response associations between TMAO and its precursors and gestational diabetes mellitus (GDM). Analyses were performed by restricted cubic spine regressions (3 knots). Parts (Ai–iii,Bi,ii) represent the dose-response associations of betaine, choline, L-carnitine, trimethylamine N-oxide (TMAO) and trimethylamine (TMA), respectively.
See this image and copyright information in PMC

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