Jinnan Liu1, Jing Li1, Kai Yang2, Junhong Leng3, Weiqin Li3, Wen Yang1, Xiaoxu Huo1, Zhijie Yu4, Ronald Cw Ma5, Gang Hu6, Zhongze Fang7, Xilin Yang8. 1. Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China. 2. Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin 300070, China. 3. Project Office, Tianjin Women and Children's Health Center, Tianjin 300070, China. 4. Population Cancer Research Program and Department of Pediatrics, Dalhousie University 15000, Halifax, Canada. 5. Department of Medicine and Therapeutics, Prince of Wales Hospital, and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong 999077, China. 6. Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA. 7. Department of Toxicology and Sanitary Chemistry, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China; Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China. Electronic address: fangzhongze@tmu.edu.cn. 8. Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin 300070, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin 300070, China; Tianjin Center for International Collaborative Research on Environment, Nutrition and Public Health, Tianjin 300070, China. Electronic address: yxl@hotmail.com.
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 (TMAR) as TMA/its precursors and TMAO conversion ratio (TMAOR) as TMAO/TMA. Copresence of high TMAR and low TMAOR 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 TMAR 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.
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 (TMAR) as TMA/its precursors and TMAO conversion ratio (TMAOR) as TMAO/TMA. Copresence of high TMAR and low TMAOR 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 TMAR 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.