Background: A number of essential trace elements are involved in glucose metabolism, but the associations between these elements and glucose levels among pregnant women are unclear. Furthermore, little is known about the joint association of these trace elements.
Methods: We used data from 1857 women enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Study, for whom trace element status (Zn, Se, Cu, Mo) was determined using plasma collected during the 1st trimester. Non-fasting glucose levels were measured during the GDM screening test. Three approaches were used to assess the joint effects of these trace elements on glucose levels. First, all four trace elements were included in a multivariable linear model and adaptive lasso was performed for model selection. Second, generalized additive models (GAMs) with model selection were fitted to allow non-linear associations. Lastly, a novel method, Bayesian Kernel Machine Regression (BKMR) was used to model the dose-response relationships of the trace element mixture in a non-parametric fashion.
Results: In the multivariable linear model, we observed significant associations of glucose levels with plasma Cu (2.4 mg/dL increase per 1 SD increase on the log scale; 95% CI: 1.1, 3.7) and plasma Mo (-1.4 mg/dL decrease per 1 SD increase on the log scale; 95% CI: -2.6, -0.1). The GAM showed suggestive evidence of non-linear positive interaction between Zn and Cu in plasma (p-value = 0.052). Similar results were observed using the BKMR approach.
Conclusion: Employing different statistical methods to study the effect of early pregnancy trace element mixtures on glucose levels, we found consistent evidences of hyperglycemic effect of Cu and hypoglycemic effect of Mo, as well as potential synergism between Zn and Cu. Future work is needed to better understand the joint effects of these elements in the context of the increasingly insulin-resistant state of pregnancy.
Y. Zheng: None. C. Zhang: None. P.L. Williams: None. M. Weisskopf: None. P.J. Parsons: None. C.D. Palmer: None. G.M. Buck Louis: None. T. James-Todd: None.
Eunice Kennedy Shriver National Institute of Child Health and Human Development