Yi Wang1, Fengjiang Sun2, Ping Wu1, Yichao Huang2,3, Yi Ye1, Xue Yang4, Jiaying Yuan5, Yan Liu6, Huayan Zeng7, Ying Wen8, Xiaorong Qi9, Chun-Xia Yang4, Yixin Wang1, Gang Liu10, Da Chen2, Liangzhong Li11, Xiong-Fei Pan1,12, An Pan1. 1. Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 2. School of Environment and Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou 511436, China. 3. Department of Toxicology, School of Public Health, Anhui Medical University, Hefei 230032, China. 4. Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China. 5. Department of Science and Education, Shuangliu Maternal and Child Health Hospital, Chengdu 610200, China. 6. Department of Obstetrics and Gynecology, Shuangliu Maternal and Child Health Hospital, Chengdu 610200, China. 7. Nutrition Department, Shuangliu Maternal and Child Health Hospital, Chengdu 610200, China. 8. Department of Communicable Diseases Control and Prevention, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China. 9. Department of Gynecology and Obstetrics, West China Second Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China. 10. Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 11. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510655, China. 12. Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Abstract
CONTEXT: While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. OBJECTIVE: We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. METHODS: This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. RESULTS: Mean age of the participants was 26.6 ± 3.7 years, and mean gestational age was 10.3 ± 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, Ptrend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, Ptrend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. CONCLUSION: Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM. The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.
CONTEXT: While the associations between thyroid markers and gestational diabetes mellitus (GDM) have been extensively studied, the results are inconclusive and the mechanisms remain unclear. OBJECTIVE: We aimed to investigate the prospective associations of thyroid markers in early gestation with GDM risk, and examine the mediating effects through lipid species. METHODS: This study included 6068 pregnant women from the Tongji-Shuangliu Birth Cohort. Maternal serum thyroid markers (free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, thyroid peroxidase antibody, and thyroglobulin antibody) were measured before 15 weeks. Deiodinase activity was assessed by fT3/fT4 ratio. Plasma lipidome were quantified in a subset of 883 participants. RESULTS: Mean age of the participants was 26.6 ± 3.7 years, and mean gestational age was 10.3 ± 2.0 weeks. Higher levels of fT4 were associated with a decreased risk of GDM (OR = 0.73 comparing the extreme quartiles; 95% CI 0.54, 0.98, Ptrend = .043), while higher fT3/fT4 ratio was associated with an increased risk of GDM (OR = 1.43 comparing the extreme quartiles; 95% CI 1.06, 1.93, Ptrend = .010) after adjusting for potential confounders. Multiple linear regression suggested that fT3/fT4 ratio was positively associated with alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, sphingomyelin 34:1, and phosphatidylcholine 40:7 (false discovery rate [FDR] adjusted P < .05). Mediation analysis indicated 67.9% of the association between fT3/fT4 ratio and GDM might be mediated through the composite effect of these lipids. CONCLUSION: Lower concentration of serum fT4 or higher fT3/fT4 ratio in early pregnancy was associated with an increased risk of GDM. The association of fT3/fT4 ratio with GDM was largely mediated by specific lipid species.
Authors: Lore Raets; Caro Minschart; Annick Van den Bruel; Emmelien Van den Bogaert; Paul Van Crombrugge; Carolien Moyson; Johan Verhaeghe; Sofie Vandeginste; Hilde Verlaenen; Chris Vercammen; Toon Maes; Els Dufraimont; Nele Roggen; Christophe De Block; Yves Jacquemyn; Farah Mekahli; Katrien De Clippel; Anne Loccufier; Annouschka Laenen; Roland Devlieger; Chantal Mathieu; Brigitte Decallonne; Katrien Benhalima Journal: J Clin Med Date: 2022-08-26 Impact factor: 4.964