Ceramides and their interactive effects with trimethylamine-N-oxide metabolites on risk of gestational diabetes: A nested case-control study

Abstract

Aims: To explore associations between ceramides in early pregnancy and gestational diabetes mellitus (GDM); and interactions between ceramides and trimethylamine N-oxide (TMAO) metabolites for GDM.

Methods: We organized a 1:1 nested case-control study (n = 486) from a prospective cohort of pregnant women. Conditional logistic regression and additive interaction were performed to examine relationships between ceramides and TMAO metabolites for GDM. We defined trimethylamine (TMA) conversion ratio (TMA_R) as TMA/its precursors and TMAO conversion ratio (TMAO_R) as TMAO/TMA. Copresence of high TMA_R and low TMAO_R indicated TMA accumulation status.

Results: High ceramides 18:0 (per SD), 18:1 (per SD) and low ceramide 24:0 (≤ 3.60 nmol/mL) were associated with increased GDM risk (OR: 1.69, 1.72 & 3.59, respectively). High TMA enhanced the OR of low ceramide 24:0 for GDM from 1.53 (95%CI: 0.88-2.66) to 10.3 (2.83-37.5), high TMA_R enhanced it from 1.31 (0.67-2.56) to 24.3 (6.57-89.5) and TMA accumulation enhanced it from 1.42 (0.72-2.77) to 25.5 (6.80-95.7), with all additive interactions being significant. However, the interactions between high ceramide 18 and TMAO metabolites were not significant.

Conclusions: High ceramides 18:0, 18:1 and low ceramide 24:0 in early pregnancy were associated with increased GDM risk. Notably, TMA accumulation greatly amplified the risk-promoting effect of low ceramide 24:0 for GDM.

Keywords: Ceramides; Gestational diabetes mellitus; Trimethylamine N-oxide metabolism.