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Perfluoroalkyl substances and beta cell deficient diabetes.

ABSTRACT: Perfluoroalkyl substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type.6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: type 1 (n=820), type 2 (n=4,291), or uncategorized diabetes (n=1,349, missing data on diabetes type or diabetes based on blood sugar at study entry). Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononaoic acid (PFNA).PFAS levels were significantly lower in those with diabetes, and lowest in those with type 1 diabetes. In age and sex adjusted analyses, ORs (CI) for type 1, type 2, and uncategorized diabetes compared to no diabetes were 0.59 (0.54-0.64), 0.74 (0.71-0.77), 0.84 (0.78-0.90), respectively for PFHxS; 0.69 (0.65-0.74), 0.87 (0.89-0.91), 0.92 (0.88-0.97), respectively for PFOA; 0.65 (0.61-0.70), 0.86 (0.82-0.90), 0.93 (0.86-1.03), respectively for PFOS; and 0.65 (0.57-0.74), 0.94 (0.88-1.00), 0.95 (0.85-1.06), respectively for PFNA. Further adjustment for eGFR and other covariates did not eliminate these inverse associations.PFAS levels were negatively associated with diabetes. This inverse relationship was strongest for type 1 diabetes, suggesting the relationship with serum PFAS may vary with the severity of islet cell deficiency.

SUBMITTER: Conway B

PROVIDER: S-EPMC5556924 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Perfluoroalkyl substances and beta cell deficient diabetes.

Conway Baqiyyah B Innes Karen E KE Long Dustin D

Journal of diabetes and its complications 20160504 6

<h4>Aims</h4>Perfluoroalkyl substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type.<h4>Methods</h4>6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: type 1 (n=820), type 2 (n=4,291), or uncategorized diabetes (n=1,349, missing data on diabetes typ ...[more]

PMID: 27311784

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Project description:BackgroundPer- and polyfluoroalkyl substances (PFASs) are a growing public health concern. Some longer chain PFASs bioaccumulate and many compounds persist in the environment for long time periods. Recent studies have established their ability to pass through placenta, yet data on the transplacental transfer efficiency and partitioning of short and long chain PFASs in blood matrices are limited.ObjectivesTo assess predictors of the partitioning of 17 PFAS compounds detected in the maternal serum, umbilical cord serum and whole cord blood samples from matched mother-newborn pairs from two Faroe Islands cohorts.MethodsWe examined 151 mother-newborn pairs from two successive Faroese birth cohorts. Cord:maternal serum (transplacental transfer) and serum:whole cord blood (blood partitioning) ratios were estimated for 17 PFAS compounds. We also examined the relationships of these ratios with maternal, newborns', and physico-chemical properties using multivariable regression analyses.ResultsModerate to high correlations were observed between maternal and cord serum PFAS concentrations (ρ: 0.41 to 0.95), indicating significant transfer of these compounds from the mother to the fetus. Median transplacental transfer ratios were generally below 1, except for perfluorooctane sulfonamide (FOSA), and ranged between 0.36 for perfluorodecanoate (PFDA) and perfluoroundecanoate (PFUnDA) and 1.21 for FOSA. Most PFASs exhibited a preference to the serum component of the blood, except FOSA and perfluoroheptanoate (PFHpA), with blood partitioning ratios ranging from 0.36 for FOSA to 2.75 for PFUnDA. Both the functional groups and carbon chain length of different PFASs were important predictors of transplacental transfer and blood partitioning. We observed a U-shaped relationship between transplacental transfer ratios and carbon chain length for perfluorocarboxylates and perfluorosulfonates. Importantly, gestational diabetes was also a strong predictor of transplacental transfer ratios, with significantly higher transfer in mothers with gestational diabetes.ConclusionsOur findings provide a better understanding of the transplacental transfer and blood partitioning of a large number of PFAS compounds. Results elucidate the importance of chemical structure for future risk assessments and choice of appropriate blood matrices for measurement of PFAS compounds.

Project description:Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies.Our objective was to examine the associations between PFAS exposures and subsequent incidence of T2D in the Nurses' Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations.A prospective nested case-control study of T2D was conducted among participants who were free of diabetes, cardiovascular disease, and cancer in 1995-2000 [(mean±SD): 45.3±4.4 y) of age]. We identified and ascertained 793 incident T2D cases through 2011 (mean±SD) years of follow-up: 6.7±3.7 y). Each case was individually matched to a control (on age, month and fasting status at sample collection, and menopausal status and hormone replacement therapy). Plasma concentrations of five major PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonate, perfluorononanoic acid, and perfluorodecanoic acid were measured. Odds ratios (ORs) of T2D by PFAS tertiles were estimated by conditional logistic regression.Shorter breastfeeding duration and higher intake of certain foods, such as seafood and popcorn, were significantly associated with higher plasma concentrations of PFASs among controls. After multivariate adjustment for T2D risk factors, including body mass index, family history, physical activity, and other covariates, higher plasma concentrations of PFOS and PFOA were associated with an elevated risk of T2D. Comparing extreme tertiles of PFOS or PFOA, ORs were 1.62 (95% CI: 1.09, 2.41; ptrend=0.02) and 1.54 (95% CI: 1.04, 2.28; ptrend=0.03), respectively. Other PFASs were not clearly associated with T2D risk.Background exposures to PFASs in the late 1990s were associated with higher T2D risk during the following years in a prospective case-control study of women from the NHSII. These findings support a potential diabetogenic effect of PFAS exposures. https://doi.org/10.1289/EHP2619.

Project description:Importance:Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors. Objectives:To determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association. Design, Setting, and Participants:This prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018. Interventions and Exposures:The initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden. Main Outcomes and Measures:Weight, waist circumference, and hip girth were measured at baseline and at scheduled visits. Results:Of the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P?=?.01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (-0.59 kg; 95% CI, -1.80 to 0.62 kg; P?=?.34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P?=?.02) but not the lifestyle intervention group (-0.09 cm; 95% CI, -0.82 to 0.63 cm; P?=?.80). No associations were observed for changes in mean waist circumference. Conclusions and Relevance:Among adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals. Trial Registration:ClinicalTrials.gov Identifier: NCT00004992 and NCT00038727.

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Perfluoroalkyl substances and beta cell deficient diabetes.

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Perfluoroalkyl substances and beta cell deficient diabetes.

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