Renal function and risk of gestational diabetes mellitus: the potential mediating role of carnitine metabolites

Xue Yang; Jieru Peng; Fengjiang Sun; Ping Wu; Yi Wang; Ying Xu; Yuwei Lai; Jiaying Yuan; Shanshan Zhang; Limiao Jiang; Yayi Hu; Xiaojuan Liu; Gang Liu; Chunxia Yang; Da Chen; An Pan; Xiong-Fei Pan

doi:10.1210/clinem/dgae881

Renal function and risk of gestational diabetes mellitus: the potential mediating role of carnitine metabolites

J Clin Endocrinol Metab. 2024 Dec 18:dgae881. doi: 10.1210/clinem/dgae881. Online ahead of print.

Authors

Xue Yang^{1

2}, Jieru Peng¹, Fengjiang Sun³, Ping Wu⁴, Yi Wang⁵, Ying Xu⁶, Yuwei Lai⁴, Jiaying Yuan⁷, Shanshan Zhang¹, Limiao Jiang⁴, Yayi Hu⁸, Xiaojuan Liu⁹, Gang Liu¹⁰, Chunxia Yang¹¹, Da Chen³, An Pan⁴, Xiong-Fei Pan^{1

12

13}

Affiliations

¹ Section of Epidemiology and Population Health & Department of Gynecology and Obstetrics, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children & Children's Medicine Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu Sichuan, 610041, China.
² MED-X institute, Center for Immunological and Metabolic Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
³ School of Environment, Guangdong Key Laboratory of Environmental Pollution and Health, Jinan University, Guangzhou, Guangdong, 510632, China.
⁴ 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, Hubei, 430030, China.
⁵ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
⁶ Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, China.
⁷ Department of Science and Education & Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, 610200, China.
⁸ Department of Obstetrics and Gynecology, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
⁹ Department of Laboratory Medicine, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
¹⁰ Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, Ministry of Education Key Lab of Environment and Health, and State Key Laboratory of Environment Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
¹¹ Department of Epidemiology and Biostatistics, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
¹² West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
¹³ Shuangliu Institute of Women's and Children's Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, 610200, China.

PMID: 39691037
DOI: 10.1210/clinem/dgae881

Abstract

Context: Renal function may play a crucial role in the development of gestational diabetes mellitus (GDM). However, prospective studies on this topic are scarce and the mechanisms remain unclear.

Objective: To assess the associations of early-pregnancy renal function with GDM and the mediating role of carnitine metabolites.

Methods: The study was based on the Tongji-Huaxi-Shuangliu Birth Cohort. Renal function was assessed before 15 weeks of gestation. GDM was diagnosed at 24-28 weeks of gestation by a 2-h oral glucose tolerance test. Multivariable logistic regression was utilized to estimate the associations of renal function indicators with GDM. Plasma carnitine metabolites in early pregnancy were quantified using ultrahigh-performance liquid chromatography-tandem mass spectrometry. Mediation analyses were applied to assess the mediating effects of carnitines.

Results: The mean age of 6,770 participants was 26.6 ± 3.7 years. Serum uric acid, uric acid to creatinine ratio, and estimated glomerular filtration rate (eGFR) were positively associated with GDM, and the odds ratios (ORs) were 1.23 (95% confidence interval, CI, 1.11, 1,36), 1.31 (1.19, 1.45), and 1.15 (1.04, 1.27) for each 1 standard deviation (SD) increment. Increased creatinine, creatinine to weight ratio, and cystatin C were associated with lower GDM risk with ORs of 0.88 (0.80, 0.97), 0.88 (0.78, 0.99), and 0.89 (0.80, 0.98) for each log-SD increment. Serum creatinine-, creatinine to weight ratio-, and eGFR-related carnitine score played positive mediating roles, and the mediation proportions were 43.1%, 81.9%, and 56.7%, respectively.

Conclusion: Renal function should be monitored for GDM, and the potential roles of carnitine metabolites require further evaluation and validation.

Keywords: birth cohort; carnitine; gestational diabetes mellitus; mediation; renal function.

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