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 This work aimed 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 routinely assessed before 15 gestational weeks. Plasma carnitine metabolites in early pregnancy were quantified using ultrahigh-performance liquid chromatography-tandem mass spectrometry. GDM was diagnosed at 24 to 28 gestational weeks by a 2-hour oral glucose tolerance test. Multivariable logistic regression was used to examine the associations of renal function indicators with GDM. Mediation analyses were applied to assess the mediating effects of carnitines. Results The mean age of 6770 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 (95% CIs) were 1.67 (95% CI, 1.25-2.23), 1.94 (1.47-2.57), and 1.53 (1.17-2.01) for the extreme-quartile comparison. Increased creatinine, cystatin C, and creatinine to weight ratio were associated with lower GDM risk, with ORs of 0.62 (0.47-0.82), 0.72 (0.52-0.99), and 0.69 (0.53-0.91) for the extreme-quartile comparison. Serum creatinine-, creatinine to weight ratio-, and eGFR-related carnitine scores 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.