Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
Key Laboratory of Liaoning Tumor Clinical Metabolomics, Jinzhou, Liaoning, China.
J Clin Endocrinol Metab. 2019 Nov 1;104(11):5529-5539. doi: 10.1210/jc.2019-00710.
This study aimed to investigate the associations between trimethylamine N-oxide (TMAO) and related metabolites in early pregnancy and the risk of gestational diabetes mellitus (GDM).
A prospective cohort of 22,302 pregnant women from 2010 to 2012 in Tianjin, China, was used to perform a nested case-control study. A total of 243 women with GDM and 243 women without GDM matched by maternal age (±1 year) were used as cases and controls, respectively. Conditional logistic regression and restricted cubic spline were used to examine the full-range risk associations between individual TMAOs metabolites at the first antenatal care visit with GDM. Trimethylamine conversion ratio (TMAR) was defined as trimethylamine (TMA)/its precursors, and trimethylamine N-oxide conversion ratio (TMAOR) was defined as TMAO/TMA. An additive interaction between high TMAR and low TMAOR indicates a state of TMA accumulation, and a mathematical interaction between high TMAR and high TMAOR indicates accumulation of TMAO.
TMA was linearly associated with GDM, whereas TMA precursors and TMAO were inversely associated with GDM with clear threshold effects, i.e., 16 nmol/mL for TMAO, 200 nmol/mL for betaine, 112 nmol/mL for l-carnitine, and 110 and 270 nmol/mL for cholinechloride (a U-shaped relationship). Copresence of TMAR >0.35 and TMAOR ≤0.15 was associated with a markedly higher OR (11.16; 95% CI, 5.45 to 22.8), compared with TMAR >0.35 only (OR = 1.71; 95% CI, 0.42 to 6.95) or TMAOR ≤0.15 only (OR = 2.06; 95% CI, 1.09 to 3.90), with a significant additive interaction. However, the mathematical interaction was nonsignificant.
TMAO metabolites in the early pregnancy were associated with the risk of GDM, whereas TMA was more likely to play a causal role in GDM.
本研究旨在探讨孕早期三甲胺 N-氧化物（TMAO）及其相关代谢物与妊娠期糖尿病（GDM）风险之间的关系。
本研究采用了 2010 年至 2012 年在中国天津进行的一项前瞻性队列研究，共纳入 22302 名孕妇进行巢式病例对照研究。共纳入 243 例 GDM 患者和 243 例年龄（±1 岁）相匹配的非 GDM 患者作为病例和对照。采用条件逻辑回归和限制性三次样条分析方法，在首次产前检查时评估个体 TMAO 代谢物与 GDM 之间的全范围风险关联。三甲胺转化率（TMAR）定义为三甲胺（TMA）/其前体，三甲胺 N-氧化物转化率（TMAOR）定义为 TMAO/TMA。高 TMAR 和低 TMAOR 之间的相加交互作用表明存在 TMA 蓄积状态，而高 TMAR 和高 TMAOR 之间的数学交互作用表明 TMAO 蓄积。
TMA 与 GDM 呈线性相关，而 TMA 前体和 TMAO 与 GDM 呈负相关，并存在明显的阈值效应，即 TMAO 为 16 nmol/mL，甜菜碱为 200 nmol/mL，左旋肉碱为 112 nmol/mL，胆碱氯化物为 110 和 270 nmol/mL（U 形关系）。TMAR>0.35 且 TMAOR≤0.15 同时存在与 TMAR>0.35 仅存在（OR=1.71；95%CI，0.42 至 6.95）或 TMAOR≤0.15 仅存在（OR=2.06；95%CI，1.09 至 3.90）相比，OR 值明显更高（11.16；95%CI，5.45 至 22.8），且存在显著的相加交互作用。然而，数学交互作用无统计学意义。
孕早期 TMAO 代谢物与 GDM 风险相关，而 TMA 更可能在 GDM 中发挥因果作用。
