Dataset Information

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

ABSTRACT:

Background

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes.

Methods

We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log₂-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction.

Results

Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines.

Conclusions

PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.

SUBMITTER: Mitro SD

PROVIDER: S-EPMC8630734 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

Mitro Susanna D SD Liu Jinxi J Jaacks Lindsay M LM Fleisch Abby F AF Williams Paige L PL Knowler William C WC Laferrère Blandine B Perng Wei W Bray George A GA Wallia Amisha A Hivert Marie-France MF Oken Emily E James-Todd Tamarra M TM Temprosa Marinella M

International journal of hygiene and environmental health 20201218

<h4>Background</h4>Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes.<h4>Methods</h4>We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total p ...[more]

PMID: 33348273

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Project description:Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996-1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N = 941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999-2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS.

Project description:BackgroundSeveral per- and polyfluoroalkyl substances (PFAS) are ubiquitous anthropogenic pollutants almost universally detected in humans. Experimental evidence indicates that PFAS alter glucose metabolism and insulin secretion. However, epidemiological studies have yielded inconsistent results.ObjectiveWe sought to examine associations between plasma PFAS concentrations, glycemic indicators, and diabetes incidence among high-risk adults.MethodsWithin the Diabetes Prevention Program (DPP), a trial for the prevention of type 2 diabetes among high-risk individuals, we quantified baseline plasma concentrations of nine PFAS among 957 participants randomized to a lifestyle intervention or placebo. We evaluated adjusted associations for plasma PFAS concentrations with diabetes incidence and key glycemic indicators measured at baseline and annually over up to 4.6 y.ResultsPlasma PFAS concentrations were similar to those reported in the U.S. population in 1999-2000. At baseline, in cross-sectional analysis, a doubling in plasma perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) concentrations was associated with higher homeostatic model assessment of insulin resistance (HOMA-IR) [βPFOS=0.39; 95% confidence interval (CI): 0.13, 0.66; βPFOA=0.64; 95% CI: 0.34, 0.94], β-cell function (HOMA-β) (βPFOS=9.62; 95% CI: 1.55, 17.70; βPFOA=15.93; 95% CI: 6.78, 25.08), fasting proinsulin (βPFOS=1.37 pM; 95% CI: 0.50, 2.25; βPFOA=1.71 pM; 95% CI: 0.72, 2.71), and glycated hemoglobin (HbA1c) (βPFOS=0.03%; 95% CI: 0.002, 0.07; βPFOA=0.04%; 95% CI: 0.001, 0.07). There was no strong evidence of associations between plasma PFAS concentrations and diabetes incidence or prospective changes in glycemic indicators during the follow-up period.ConclusionsAt baseline, several PFAS were cross-sectionally associated with small differences in markers of insulin secretion and β-cell function. However, there was limited evidence suggesting that PFAS concentrations are associated with diabetes incidence or changes in glycemic indicators during the follow-up period. https://doi.org/10.1289/EHP1612.

Project description:BackgroundHypertensive disorders of pregnancy (HDP), defined here as hypertensive disorders with onset in pregnancy (i.e., gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension), affect up to 10% of pregnancies in the United States and are associated with substantial maternal and neonatal morbidity and mortality. Per- and polyfluoroalkyl substances (PFAS) are associated with adverse cardiometabolic outcomes during pregnancy, but associations between PFAS and HDP are inconsistent and joint effects of PFAS mixtures have not been evaluated.MethodsWe studied 1,558 pregnant individuals from the Project Viva cohort, recruited during 1999-2002. We quantified concentrations of eight PFAS in plasma samples (median 9.7 weeks of gestation). Using clinical records, we calculated trimester-specific mean systolic (SBP) and diastolic (DBP) blood pressure and categorized HDP status [no HDP (normotensive & chronic hypertension), gestational hypertension, preeclampsia]. We estimated associations of individual PFAS with HDP using multinomial logistic regression and estimated associations with blood pressure using linear regression. We used Bayesian kernel machine regression (BKMR) and quantile g-computation to assess joint effects of the PFAS mixture on HDP and blood pressure measures.ResultsFour percent of participants developed preeclampsia and 7% developed gestational hypertension. We observed higher odds of gestational hypertension, but not preeclampsia, per doubling of perfluorooctanoate (PFOA) [OR = 1.51 (95% confidence interval: 1.12, 2.03)], perfluorooctane sulfonate (PFOS) [OR = 1.38 (1.04, 1.82)], and perfluorohexane sulfonate [OR = 1.28 (1.06, 1.54)] concentrations. We observed higher mean DBP per doubling of PFOA [2nd trimester (T2): 0.39 mmHg (-0.01, 0.78); 3rd trimester (T3): 0.56 mmHg (0.14, 0.98)] and PFOS [T2: 0.46 mmHg (0.11, 0.82); T3: 0.43 mmHg (0.05, 0.80)]. The PFAS mixture was positively associated with odds of gestational hypertension [75th vs. 50th percentile: OR = 1.14 (95% credible interval:1.03, 1.25), BKMR] and mean DBP [T2 = 0.17 mmHg (-0.06, 0.40); T3 = 0.22 mmHg (-0.03, 0.48), BKMR].ConclusionsThese findings suggest that exposure to certain PFAS may increase the odds of gestational hypertension during pregnancy, with potential implications for subsequent maternal and child health outcomes.

Project description:Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

Project description:BackgroundUnderstanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S.ObjectivesDetermine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age.MethodsWe described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m2). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model.ResultsLongitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS.DiscussionWe observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.

Project description:IntroductionPer- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics.MethodsWe conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998-2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline-June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption).ResultsProstate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88-1.59)] and PFOS [HR (95% CI): 1.18 (0.89-1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02-2.31) and PFOS 1.62 (1.08-2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage.ConclusionsOur findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

Dataset Information

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

Background

Methods

Results

Conclusions

Publications

Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial.

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