Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trial.

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.

Lin PD ，Cardenas A ，Hauser R ，Gold DR ，Kleinman KP ，Hivert MF ，Fleisch AF ，Calafat AM ，Sanchez-Guerra M ，Osorio-Yáñez C ，Webster TF ，Horton ES ，Oken E ... -  《-》

Per- and polyfluoroalkyl substances and blood pressure in pre-diabetic adults-cross-sectional and longitudinal analyses of the diabetes prevention program outcomes study.

The relationship of plasma concentration of per- and polyfluoroalkyl substances (PFAS) with blood pressure (BP) is uncertain. This study examined cross-sectional and prospective associations of PFAS with BP and hypertension. We quantified plasma PFAS concentrations from 957 participants enrolled in the lifestyle and placebo arms of the Diabetes Prevention Program (DPP), a randomized controlled trial with approximately 15 years of follow-up. We used multivariable linear and logistic regressions to test cross-sectional associations of six PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and perfluorononanoic acid (PFNA), with BP and hypertension prevalence, respectively, at baseline. We used generalized linear mixed models to estimate longitudinal associations between baseline PFAS and the rate of BP changes, and Cox-Proportional hazard models to estimate risk of developing hypertension relative to baseline PFAS. Models were adjusted for baseline age, sex, race/ethnicity, treatment arm, educational attainment, income, marital status, smoking habit, alcohol drinking, and diet. We tested for effect modification by the treatment arm and sex, and accounted for multiple comparisons using the False-Discovery Rate (FDR). PFAS concentrations and hypertension prevalence within the study population (65.3% female, 57.7% White, 65.3% aged 40-59 years) were comparable to the general U.S. population. Cross-sectionally, we found small but statistically significant associations of baseline plasma concentrations of PFOA with systolic BP (β per doubling: 1.49 mmHg, 95% CI: 0.29, 2.70); and MeFOSAA with hypertension (RR = 1.09 per doubling, 95% CI: 1.01, 1.19). Estimates were not statistically significant after FDR adjustment. Longitudinally, we observed null associations in the placebo arm, but some inverse associations of baseline PFOS and MeFOSAA with systolic BP in the lifestyle arm, perhaps due to regression toward the mean. Baseline PFAS concentrations also were not prospectively associated with hypertension risk. Overall, there were modest and mostly null associations of plasma PFAS concentrations with BP and hypertension.

Lin PD ，Cardenas A ，Hauser R ，Gold DR ，Kleinman KP ，Hivert MF ，Calafat AM ，Webster TF ，Horton ES ，Oken E ... -  《-》

Temporal trends of concentrations of per- and polyfluoroalkyl substances among adults with overweight and obesity in the United States: Results from the Diabetes Prevention Program and NHANES.

Understanding 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. Determine 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. We 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. Longitudinal 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. We 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.

Lin PD ，Cardenas A ，Hauser R ，Gold DR ，Kleinman KP ，Hivert MF ，Calafat AM ，Webster TF ，Horton ES ，Oken E ... -  《-》

Correlates of plasma concentrations of per- and poly-fluoroalkyl substances among reproductive-aged Black women.

Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1499 Black women aged 23-35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010-2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95 % confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. PFHxS, PFOS, PFOA, and PFNA were detected in ≥97 % of women; PFDA in 86 %; MeFOSAA in 70 %; and PFUnDA in 52 %. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95 % CI) were observed between parity (≥3 vs. 0 births) and PFHxS (-34.7; -43.0, -25.1) and PFOA (-33.1; -39.2, -26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (-31.1; -37.8, -23.7), PFHxS (-24.2; -34.5, -12.3), and PFOS (-18.4; -28.3, -7.1); recent birth (<2 years ago vs. nulliparous) and PFOA (-33.1; -39.6, -25.8), PFHxS (-29.3; -39.0, -18.1), PFNA (-25.2; -32.7, -16.8), and PFOS (-18.3; -28.3, -6.9); and intensity of menstrual bleed (heavy vs. light) and PFHxS (-18.8; -28.3, -8.2), PFOS (-16.4; -24.9, -7.1), PFNA (-10.5; -17.8, -2.6), and PFOA (-10.0; -17.2, -2.1). Current use of depot medroxyprogesterone acetate (DMPA) was positively associated with PFOS (20.2; 1.4, 42.5), PFOA (16.2; 1.5, 33.0), and PFNA (15.3; 0.4, 32.4). Reproductive factors that influence PFAS elimination showed strong associations with several PFAS (reduced concentrations with parity, recent birth, lactation, heavy menstrual bleeding; increased concentrations with DMPA use).

Wise LA ，Wesselink AK ，Schildroth S ，Calafat AM ，Bethea TN ，Geller RJ ，Coleman CM ，Fruh V ，Claus Henn B ，Botelho JC ，Harmon QE ，Thirkill M ，Wegienka GR ，Baird DD ... -  《-》

Associations of perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS mixtures with adipokines in midlife women.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure have been associated with obesity and related comorbidities, possibly through disrupting signaling pathways of adipokines. Both leptin and adiponectin can modulate metabolic processes. However, the effects of PFAS on adipokines are not well understood. We determined if serum PFAS concentrations were associated with adipokine profiles in midlife women. We examined 1245 women aged 45-56 years from the Study of Women's Health Across the Nation. Concentrations of 11 PFAS were quantified in baseline serum samples collected in 1999-2000. Linear and branched perfluorooctane sulfonic acid isomers (n-PFOS and Sm-PFOS) and their sum (PFOS), linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA) with detection frequencies >60% were included in the analysis. Adipokines including leptin, soluble leptin receptor (sOB-R), free leptin index (FLI, the ratio of leptin to sOB-R), total and high molecular weight (HMW) adiponectin were assessed in 2002-2003. We utilized multivariable linear regressions and Bayesian kernel machine regression (BKMR) to assess individual and overall joint effects of PFAS on adipokines with adjustment for age, race/ethnicity, study site, education, smoking status, physical activity, menopausal status, and waist circumference. A doubling of PFAS concentrations was associated with 7.8% (95% CI: 2.5%, 13.4%) higher FLI for PFOS, 9.4% (95% CI: 3.7%, 15.3%) for n-PFOA, 5.5% (95% CI: 2.2%, 9.0%) for EtFOSAA and 7.4% (95% CI: 2.8%, 12.2%) for MeFOSAA. Similar associations were found for leptin. Only EtFOSAA was associated with lower sOB-R concentrations (-1.4%, 95% CI: -2.7%, -0.1%). Results remained in women with overweight or obesity but not those with normal weight or underweight. No statistically significant associations were observed with total or HMW adiponectin, except for PFNA with total and HMW adiponectin observed in women with normal weight or underweight. In BKMR analysis, women with PFAS concentrations at the median and the 90th percentile had 30.9% (95% CI: 15.6%, 48.3%) and 52.1% (95% CI: 27.9%, 81.0%) higher FLI, respectively, compared with those with concentrations fixed at the 10th percentile. Some PFAS may alter circulating levels of leptin. Understanding associations between PFAS and adipokines may help elucidate whether PFAS can influence obesity and metabolic disease.

Ding N ，Karvonen-Gutierrez CA ，Herman WH ，Calafat AM ，Mukherjee B ，Park SK ... -  《-》