A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus

Yi Wang; Fengjiang Sun; Ping Wu; Yichao Huang; Yi Ye; Xue Yang; Jiaying Yuan; Yan Liu; Huayan Zeng; Ying Wen; Xiaorong Qi; Chun-Xia Yang; Yixin Wang; Gang Liu; Da Chen; Liangzhong Li; Xiong-Fei Pan; An Pan

doi:10.1210/clinem/dgab637

A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus

J Clin Endocrinol Metab. 2022 Jan 18;107(2):e804-e814. doi: 10.1210/clinem/dgab637.

Authors

Yi Wang¹, Fengjiang Sun², Ping Wu¹, Yichao Huang^{2

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 Pan^{1

12}, An Pan¹

Affiliations

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.

PMID: 34453541
DOI: 10.1210/clinem/dgab637

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.

Keywords: Birth cohort; gestational diabetes mellitus; lipidome; mediation; thyroid markers.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Biomarkers / blood
Biomarkers / metabolism
Case-Control Studies
Diabetes, Gestational / epidemiology*
Diabetes, Gestational / metabolism
Female
Humans
Incidence
Lipidomics
Lipids / blood*
Pregnancy
Pregnancy Trimester, First / blood*
Pregnancy Trimester, First / metabolism
Prospective Studies
Risk Assessment / methods
Thyroid Function Tests
Thyroid Hormones / blood*
Thyroid Hormones / metabolism
Young Adult

Substances

Biomarkers
Lipids
Thyroid Hormones