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

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.