Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes

Aidan Mcglinchey,Tim Sinioja,Santosh Lamichhane,Partho Sen,Johanna Bodin,Heli Siljander,Alex M Dickens,Dawei Geng,Cecilia Carlsson,Daniel Duberg,Jorma Ilonen,Suvi M Virtanen,Hubert Dirven,Hanne Friis Berntsen,Karin Zimmer,Unni C Nygaard,Matej Orešič,Mikael Knip,Tuulia Hyötyläinen

doi:10.1016/j.envint.2020.105935

Abstract

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.

Highlights

type 1 diabetes (T1D) is an autoimmune disease caused by destruction of insulin-secreting pancreatic beta-cells (Atkinson et al 2014)
Given the potential impact of prenatal exposure to perfluoroalkyl substances (PFAS) on cord serum lipids associated with progression to T1D, we examined whether human leukocyte antigen (HLA)-conferred risk of T1D plays a role in mediating the impact of PFAS exposure on lipids in newborn infants
By integrating PFAS exposure and metabolomic data from pregnant mothers with metabolomic data from their newborn infants, we were able to demonstrate altered cord serum metabolic signatures associated with high PFAS exposure during pregnancy and subsequently verify these findings in NOD mouse models of pre- and postnatal PFAS exposure

Summary

Introduction

T1D is an autoimmune disease caused by destruction of insulin-secreting pancreatic beta-cells (Atkinson et al 2014). Others, previously observed that children progressing to T1D-associated islet autoantibody positivity, or to overt T1D later in life, have a distinct lipidomic profile characterized by decreased blood phospholipid levels, including sphingomyelins (SMs), within the first months of life, preceding the onset of islet autoimmunity (Johnson et al 2019; Orešič et al 2008) and occurring even as early as at birth (Oresic et al 2013). The cause of these metabolic changes is currently poorly understood.

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Conclusion