McGlinchey, Aidan, Sinioja, Tim, Lamichhane, Santosh, Sen, Partho, Bodin, Johanna, Siljander, Heli, Dickens, Alex M., Geng, Dawei, Carlsson, Cecilia, Duberg, Daniel, Ilonen, Jorma, Virtanen, Suvi M., Dirven, Hubert, Berntsen, Hanne Friis, Zimmer, Karin, Nygaard, Unni C., Orešič, Matej, Knip, Mikael, and Hyötyläinen, Tuulia
• Over last decade, increasing incidence of type 1 diabetes has stabilized in Finland. • Stabilization of disease incidence coincides with tighter regulation of PFAS. • High prenatal PFAS exposure associates with decreased postnatal serum phospholipids. • High prenatal PFAS exposure associates with appearance of islet autoantibodies. • Prenatal PFAS exposure contributes to increased postnatal risk of type 1 diabetes. In the last decade, increasing incidence of type 1 diabetes (T1D) stabilized in Finland, a phenomenon that coincides with tighter regulation of perfluoroalkyl substances (PFAS). Here, we quantified PFAS to examine their effects, during pregnancy, on lipid and immune-related markers of T1D risk in children. In a mother-infant cohort (264 dyads), high PFAS exposure during pregnancy associated with decreased cord serum phospholipids and progression to T1D-associated islet autoantibodies in the offspring. This PFAS-lipid association appears exacerbated by increased human leukocyte antigen-conferred risk of T1D in infants. Exposure to a single PFAS compound or a mixture of organic pollutants in non-obese diabetic mice resulted in a lipid profile characterized by a similar decrease in phospholipids, a marked increase of lithocholic acid, and accelerated insulitis. Our findings suggest that PFAS exposure during pregnancy contributes to risk and pathogenesis of T1D in offspring. [ABSTRACT FROM AUTHOR]