Exposure to Perfluoroalkyl Substances and Glucose Homeostasis in Youth.
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ABSTRACT: Background
Exposure to per- and polyfluoroalkyl substances (PFAS), a prevalent class of persistent pollutants, may increase the risk of type 2 diabetes.Objective
We examined associations between PFAS exposure and glucose metabolism in youth.Methods
Overweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n=310) participated in annual visits for an average of 3.3±2.9y. Generalizability of findings were tested in young adults from the Southern California Children's Health Study (CHS; n=135) who participated in a clinical visit with a similar protocol. At each visit, oral glucose tolerance tests were performed to estimate glucose metabolism and β-cell function via the insulinogenic index. Four PFAS were measured at baseline using liquid chromatography-high-resolution mass spectrometry; high levels were defined as concentrations >66th percentile.Results
In females from the SOLAR, high perfluorohexane sulfonate (PFHxS) levels (≥2.0 ng/mL) were associated with the development of dysregulated glucose metabolism beginning in late puberty. The magnitude of these associations increased postpuberty and persisted through 18 years of age. For example, postpuberty, females with high PFHxS levels had 25-mg/dL higher 60-min glucose (95% CI: 12, 39mg/dL; p<0.0001), 15-mg/dL higher 2-h glucose (95% CI: 1, 28mg/dL; p=0.04), and 25% lower β-cell function (p=0.02) compared with females with low levels. Results were largely consistent in the CHS, where females with elevated PFHxS levels had 26-mg/dL higher 60-min glucose (95% CI: 6.0, 46mg/dL; p=0.01) and 19-mg/dL higher 2-h glucose, which did not meet statistical significance (95% CI: -1, 39mg/dL; p=0.08). In males, no consistent associations between PFHxS and glucose metabolism were observed. No consistent associations were observed for other PFAS and glucose metabolism.Discussion
Youth exposure to PFHxS was associated with dysregulated glucose metabolism in females, which may be due to changes in β-cell function. These associations appeared during puberty and were most pronounced postpuberty. https://doi.org/10.1289/EHP9200.
SUBMITTER: Goodrich JA
PROVIDER: S-EPMC8409228 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7331829 | biostudies-literature
Project description:BackgroundPer- and polyfluoroalkyl substances (PFASs) exposure is ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown.ObjectiveThe aim of this project is to investigate the association between PFASs exposure and altered metabolic pathways linked to increased cardiometabolic risk in young adults.MethodsA total of 102 young adults with 82% overweight or obese participants were enrolled from Southern California between 2014 and 2017. Cardiometabolic outcomes were assessed including oral glucose tolerance test (OGTT) measures, body fat and lipid profiles. High-resolution metabolomics was used to quantify plasma exposure levels of three PFAS congeners and intensity profiles of the untargeted metabolome. Fasting concentrations of 45 targeted metabolites involved in fatty acid and lipid metabolism were used to verify untargeted metabolomics findings. Bayesian Kernel Machine Regression (BKMR) was used to examine the associations between PFAS exposure mixture and cardiometabolic outcomes adjusting for covariates. Mummichog pathway enrichment analysis was used to explore PFAS-associated metabolic pathways. Moreover, the effect of PFAS exposure on the metabolic network, including metabolomic profiles and cardiometabolic outcomes, was investigated.ResultsHigher exposure to perfluorooctanoic acid (PFOA) was associated with higher 30-minute glucose levels and glucose area under the curve (AUC) during the OGTT (p < 0.001). PFAS exposure was also associated with altered lipid pathways, which contributed to the metabolic network connecting PFOA and higher glucose levels following the OGTT. Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol (p = 0.006), which itself was associated with higher 30-minute glucose (p = 0.006).ConclusionsIncreased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate.
| S-EPMC8009052 | biostudies-literature
Project description:BackgroundPerfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited.MethodsWe studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex.ResultsChildren with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring.ConclusionsWe found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487;?http://dx.doi.org/10.1289/EHP303.
| S-EPMC5332186 | biostudies-literature
Project description:BackgroundPerfluoroalkyl substances (PFASs) are used in surface coatings that resist stains, grease, and water.MethodsThe association between in utero PFAS exposure and girls' body fatness at age 9 was analyzed in The Avon Longitudinal Study of Parents and Children (UK). Maternal serum [median 15 weeks: interquartile range (IQR) 10 and 28 weeks of gestation] was analyzed for perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA). Body composition was measured by dual X-ray emission absorptiometry, and percent total body fat (%BF) was calculated. Associations between PFASs and body fatness were modeled by multivariable linear regression.ResultsAmong 359 girls, median (IQR) %BF was 27.5 (IQR 21.7-34.6). Median (IQR) concentrations (all ng/mL) were 3.7 (2.9-4.8) for PFOA, 19.8 (15.0-25.3) for PFOS, 1.6 (1.3-2.2) for PFHxS, and 0.5 (0.4-0.7) for PFNA. Maternal PFAS concentrations were not significantly associated with daughters' total %BF overall. Mothers' educational status modified associations for PFOA and PFOS with %BF (P-interactions: 0.005 and 0.02, respectively). %BF was higher [1.4%; 95% confidence interval (95% CI): 0.3 to 2.5] for each one unit (ng/mL) higher PFOA among girls with mothers in the middle education group, but lower (-0.6%; 95% CI: -1.12 to -0.04) for the corresponding comparison among girls with mothers with the highest education. %BF was lower (-0.2%; 95% CI: -0.3 to -0.1) for each one unit higher PFOS among girls with the most educated mothers.ConclusionsPrenatal exposure to PFOA and PFOS was associated with girls' %BF within some strata of maternal education status. PFHxS and PFNA were not associated with %BF.
| S-EPMC5444423 | biostudies-literature
Project description:ObjectiveGestational perfluoroalkyl substances exposure has been associated with decreased birthweight. We determined if gestational perfluoroalkyl substances exposure was associated with fetal metabolic markers using data from the HOME Study, a prospective birth cohort of pregnant women and their children in Cincinnati, Ohio.MethodsMaternal serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid, and perfluorohexane sulfonic acid were quantified. We measured neonatal adipocytokine (leptin and adiponectin) concentrations in umbilical cord serum, and estimated percent differences with a 2-fold increase in maternal perfluoroalkyl substances concentrations among 230 mother-infant pairs.ResultsMedian maternal serum PFOA and PFOS concentrations were 5.6 ng/mL and 14 ng/mL, respectively. Leptin was positively correlated with infant birthweight (p < 0.001). There were no statistically significant associations between maternal perfluoroalkyl substances and neonatal adipocytokine concentrations; each 2-fold increase in PFOA was associated with a non-significant increase in leptin (5%; 95% CI: -10, 22) and adiponectin (7%; 95% CI: -4, 19).ConclusionDespite known associations with reduced birthweight, gestational serum perfluoroalkyl substances concentrations were not associated with neonatal adipocytokine concentrations. Further exploration of pathways of perfluoroalkyl substances associated changes in birthweight may help identify biomarkers that could be used to identify at-risk populations and develop interventions.
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Project description:ObjectiveTo examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children.MethodsForty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile.ResultsEach ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8-52.4) and 10.2 mg/dL (95% CI: 2.7-17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5-34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns.ConclusionsThis proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms.
| S-EPMC6555482 | biostudies-literature
Project description:Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity.We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood.We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex.Median (25-75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1-7.7), 24.8 (18.4-33.9), 2.4 (1.6-3.8), and 0.6 (0.5-0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m2 (95% CI: -0.05, 0.48) higher body mass index, 0.76 mm (95% CI: -0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m2 (95% CI: -0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures.In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health Perspect 125:467-473;?http://dx.doi.org/10.1289/EHP246.
| S-EPMC5332178 | biostudies-other
Project description:INTRODUCTION:Exposure to perfluoroalkyl substances (PFAS), synthetic and persistent chemicals used in commercial and industrial processes, are associated with cardiometabolic dysfunction and related risk factors including reduced birth weight, excess adiposity, and dyslipidemia. Identifying the metabolic changes induced by PFAS exposure could enhance our understanding of biological pathways underlying PFAS toxicity. OBJECTIVE:To identify metabolic alterations associated with serum concentrations of four PFAS in children using a metabolome-wide association study. METHODS:We performed untargeted metabolomic profiling by liquid chromatography with ultra-high-resolution mass spectrometry, and separately quantified serum concentrations of perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorononanoic acid, and perfluorohexanesulfonic acid (PFHxS) for 114 8-year old children from Cincinnati, OH. We evaluated associations between each serum PFAS concentration and 16,097 metabolic features using linear regression adjusted for child age, sex, and race with a false discovery rate?<?20%. We annotated PFAS-associated metabolites and conducted pathway enrichment analyses. RESULTS:Serum PFAS concentrations were associated with metabolic features annotated primarily as lipids and dietary factors. Biological pathways associated with all four PFAS included arginine, proline, aspartate, asparagine, and butanoate metabolism. CONCLUSIONS:In this cross-sectional study, childhood serum PFAS concentrations were correlated with metabolic pathways related to energy production and catabolism. Future studies should determine whether these pathways mediate associations between PFAS exposure and childhood cardiometabolic health.
| S-EPMC7172933 | biostudies-literature
Project description:Perfluoroalkyl substances (PFAS) were among various persistent organic pollutants suspected to have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence on the association between prenatal PFAS exposure and child neurodevelopment is limited and inconsistent. This study evaluated the association between prenatal PFAS exposure and child cognitive outcomes measured at 5 different time points in a population prenatally exposed to the WTC disaster. The study population included 302 pregnant women in the Columbia University WTC birth cohort enrolled between December 13, 2001 and June 26, 2002 at three hospitals located near the WTC site: Beth Israel, St. Vincent's, and New York University Downtown. We evaluated the association between prenatal exposure to four PFAS (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA)) and child neurodevelopment measured using the Bayley Scales of Infant Development (BSID-II) at approximately 1, 2 and 3 years of age and using The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at approximately 4 and 6 years of age. Geometric mean (range) concentrations of PFAS were 6.03 (1.05, 33.7), 2.31 (0.18, 8.14), 0.43 (<LOQ, 10.3) and 0.67 (<LOQ, 15.8) ng/mL for PFOS, PFOA, PFNA and PFHxS, respectively. Several PFAS were associated with increases in cognitive outcomes in females and overall (males and females combined). Child sex modified the association between PFOS and the mental development index measured using BSID-II, with the observed relationship being positive for females and negative for males. Through principal component analyses, we observed a negative relationship between PFNA and the psychomotor development index measured using BSID-II and the verbal IQ measured using WPPSI. Our results suggest a sex- and compound-specific relationship between prenatal PFAS exposures and childhood neurodevelopment.
| S-EPMC7362877 | biostudies-literature
Project description:BACKGROUND:Evidence on the association between exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) and blood glucose concentrations in pregnant women is inconsistent. This study aimed to examine the association between PFAS exposure and the concentrations of fasting plasma glucose (FPG) and one-hour plasma glucose (1 h-PG) after a 50-g oral glucose tolerance test in pregnant women. METHODS:The study was based on the Shanghai-Minhang Birth Cohort, in which 1292 pregnant women were recruited. Among them, 981 women provided blood samples (at 12-16 gestational weeks) for PFAS measurement. FPG data collected from 856 women at 12-20 GW and 1 h-PG data collected from 705 women at 20-28 GW were obtained through medical records from the routine prenatal care system. High FPG or 1 h-PG was defined as ≥90th percentile of FPG or 1 h-PG. The analysis of eight PFASs was conducted in this study: perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), and perfluorotridecanoic acid (PFTrDA). The odds ratios (ORs) and associated 95% confidence intervals (CIs) were estimated to determine the associations of each PFAS compound with high FPG and 1 h-PG from a logistic regression model. RESULTS:After adjustment for potential confounders, most PFASs were positively associated with high 1 h-PG concentrations. The OR for high 1 h-PG concentrations was 1.87 (95% CI: 1.15-3.05) with a one log unit increase of PFOS; similar associations were observed for PFNA (OR: 2.15, 95% CI: 1.24-3.74), PFDA (OR: 1.61, 95% CI: 1.10-2.44), PFUdA (OR: 1.71, 95% CI: 1.12-2.62), and PFDoA (OR: 1.34, 95% CI: 1.00-1.81). When the PFAS concentrations were categorized into three groups by tertiles, the highest tertiles of PFOS, PFOA, PFNA, PFDA, PFDoA, and PFTrDA had a statistically significant increase in the risk of high 1 h-PG concentrations compared with the lowest tertiles. No statistically significant association was observed between PFAS exposure and high FPG. CONCLUSION:PFAS exposure was associated with an increased risk of high 1 h-PG among pregnant women, but no such association was observed for FPG.
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