Aluminum Exposure and Gestational Diabetes Mellitus: Associations and Potential Mediation by n-6 Polyunsaturated Fatty Acids

As the earth's third most abundant element with various industrial applications, aluminum (Al) has received increasing concerns over its potential adverse health effects. Although Al exposure has been suggested to increase the risks of type 2 diabetes, little has been done to explore Al exposure in pregnant women and potential impact on the incidence of gestational diabetes mellitus (GDM). Our present study demonstrated positive associations between Al concentrations in maternal plasma collected in the first trimester of pregnancy and GDM risks (P-trend < 0.001) based on a nested case-control study from Wuhan, China, including 305 GDM cases and 305 healthy controls. The highest tertile of plasma Al concentrations corresponded to an odds ratio of 4.03 (95% confidence interval: [2.14, 7.58]) relative to the lowest tertile, after the adjustment for established GDM risk factors and other plasma metals. We also observed significant correlations between plasma Al and several plasma polyunsaturated fatty acids (PUFA; e.g., linoleic acid 18:2 n-6) levels. In addition, mediation effects on the associations of Al exposure with GDM risks were observed for n-6 PUFAs (estimated mediation percentage: 48.3%) and total PUFAs (48.9%). Our study is not only by far the largest study of its kind to demonstrate maternal Al exposure and the association with GDM risks, but it also offers an insight into the potential mediation roles of n-6 PUFAs in an epidemiological setting. These findings contribute to a better understanding of perinatal Al exposure and GDM risks.