Environmental contaminants, sex hormones and SHBG in an elderly population.

Introduction: Effects of environmental contaminants (ECs) on endocrine systems have been reported, but few studies assessed associations between ECs and sex hormones (SH) in elderly. Aim of this study was to investigate whether blood concentrations of four classes of ECs were associated with SH concentrations in elderly.

Methods: Samples from participants of the cross-sectional population-based Prospective Investigation of the Vasculature in Uppsala Seniors study (PIVUS, 70-year-old men and women, n = 1016) were analyzed using validated mass spectrometry-based methods for SH (testosterone (T), dihydrotestosterone (DHT), estrone and estradiol (E2)); 23 persistent organic pollutants (POPs); 8 perfluoroalkyl substances (PFAS); 4 phthalates and 11 metals.

Correlation between environmental pollutant exposure and cardiopulmonary health by serum biomarker analysis in the Swedish elderly population.

Persistent organic pollutants (POPs) affect human health through the aryl hydrocarbon receptor (AhR) pathway and are implicated in mitochondrial dysfunction. Using data from the PIVUS study, we investigated the associations of serum AhR ligand (POP)-mediated luciferase activity (AhRL), mitochondrial ATP production inhibiting substances (MIS-ATP), and those affecting reactive oxygen species (MIS-ROS) with several metabolic syndrome (MetS) and cardiopulmonary function parameters. These include insulin resistance (HOMA-IR), inflammation, oxidative stress, and cardiopulmonary variables (FVC, FEV1, LV-EF, CCA distensibility).

Assessing the performance of a targeted absolute quantification isotope dilution liquid chromatograhy tandem mass spectrometry assay versus a commercial nontargeted relative quantification assay for detection of three major perfluoroalkyls in human blood.

Isotope dilution ultrahigh-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) is commonly used for trace analysis of polyfluoroalkyl and perfluoroalkyl substances (PFAS) in difficult matrices. Commercial nontargeted analysis of major PFAS where relative concentrations are obtained cost effectively is rapidly emerging and is claimed to provide comparable results to that of absolute quantification using matrix matched calibration and isotope dilution UHPLC-MS/MS. However, this remains to be demonstrated on a large scale.

Plasma levels of per- and polyfluoroalkyl substances (PFAS) and cardiovascular disease - Results from two independent population-based cohorts and a meta-analysis.

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD).

Objectives: To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies.

Plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with altered levels of proteins previously linked to inflammation, metabolism and cardiovascular disease.

Background: Per- and polyfluoroalkyl substances (PFAS) have been linked to immunotoxic and cardiometabolic effects in both experimental and epidemiological studies, but with conflicting results.

Aim: The aim of the present study was to investigate potential associations between plasma PFAS levels and plasma levels of preselected proteomic biomarkers previously linked to inflammation, metabolism and cardiovascular disease.

Methods: Three PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS)) were measured by non-targeted metabolomics and 249 proteomic biomarkers were measured by the proximity extension assay (PEA) in plasma from 2,342 individuals within the Epidemiology for Health (EpiHealth) study from Sweden (45-75 years old, 50.

Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles.

Background: Perfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.

Objective: We aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.

Associations between per- and polyfluoroalkyl substances (PFAS) and diabetes in two population-based cohort studies from Sweden.

Background: Per- and polyfluoroalkyl substances (PFAS) have been suggested to contribute to the development of metabolic diseases such as obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). However, evidence from epidemiological studies remain divergent. The aim of the present study was to evaluate associations between PFAS exposure and prevalent diabetes in a cross-sectional analysis and fasting glucose in a longitudinal analysis.

Mixtures of environmental contaminants and diabetes.

Background: Many studies have been published on the relationships between different environmental contaminants and diabetes. In these studies, the environmental contaminants have most often been evaluated one by one, but in real life we are exposed to a mixture of contaminants that interact with each other.

Objective: The major aim of this study was to see if a mixture of contaminants could improve the prediction of incident diabetes, using machine learning.

Obesity II: Establishing causal links between chemical exposures and obesity.

Obesity is a multifactorial disease with both genetic and environmental components. The prevailing view is that obesity results from an imbalance between energy intake and expenditure caused by overeating and insufficient exercise. We describe another environmental element that can alter the balance between energy intake and energy expenditure: obesogens.

Changes in plasma levels of per- and polyfluoroalkyl substances (PFAS) are associated with changes in plasma lipids - A longitudinal study over 10 years.

Background: Associations between per- and polyfluoroalkyl substances (PFAS), mainly PFOS and PFOA, and increased blood lipids have been reported primarily from cross-sectional studies. The aim of the present study was to investigate associations between multiple PFAS and blood lipids in a longitudinal fashion.

Methods: A total of 864 men and women aged 70 years and free from lipid medication were included from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study from Uppsala Sweden, 614 and 404 of those were reinvestigated at age 75 and 80.

Serum levels of perfluoroalkyl substances (PFAS) and body composition - A cross-sectional study in a middle-aged population.

Background: It has been suggested that per- and polyfluoroalkyl substances (PFAS) are endocrine disruptors with a potential to influence fat mass.

Objective: The primary hypothesis tested was that we would find positive relationships for PFAS vs measures of adiposity.

Methods: In 321 subjects all aged 50 years in the POEM study, five PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA)) were measured in serum together with a Dual-energy X-ray absorptiometry (DXA) scan for determination of fat and lean mass.

Concentrations of nine endogenous steroid hormones in 70-year-old men and women.

Objectives: Circulating concentrations of endogenous steroids have systemic implications on health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI and to present concentrations in apparently healthy subjects.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly.

Background: High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time.

Methods: Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.

The associations between p,p'-DDE levels and plasma levels of lipoproteins and their subclasses in an elderly population determined by analysis of lipoprotein content.

Background: Lipoproteins at aberrant levels are known to play a role in cardiovascular disease. The metabolite of the insecticide dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), physically associates with lipids and accumulates in adipose tissue. Little is known about which lipoproteins associate with p,p'-DDE.

Are Persistent Organic Pollutants Linked to Lipid Abnormalities, Atherosclerosis and Cardiovascular Disease? A Review.

The term persistent organic pollutants (POPs) denotes chemicals with known or suspected adverse health effects in animals or humans and with chemical properties that make them accumulate in the environment, including animals or humans. Lipid-soluble POPs, like dioxins, polychlorinated biphenyls (PCBs) and organochlorine pesticides are transported by lipoproteins and accumulate in adipose tissue. High levels of these compounds in the circulation have been associated with elevated cholesterol and triglycerides in cross-sectional studies and with an increase in mainly low-density lipoprotein cholesterol in a longitudinal study.

Lipophilic Environmental Chemical Mixtures Released During Weight-Loss: The Need to Consider Dynamics.

Intentional weight loss can increase health risk in the long-term, despite short-term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs.

Urinary bisphenol A and serum lipids: a meta-analysis of six NHANES examination cycles (2003-2014).

Background: Mounting evidence from both experimental and epidemiological studies suggest that exposure to the endocrine disruptor bisphenol A (BPA) has a role in metabolic disorders. The aim of the present study was to assess whether urinary BPA concentrations were associated with dyslipidaemia in children (≤17 years old) and adults (≥18 years old) by performing a meta-analysis of data from six cycles (2003-2014) in the National Health and Nutrition Examination Survey (NHANES).

Methods: We conducted a meta-analysis of data from 4604 children and 10 989 adult participants who were part of a substudy of urinary BPA measurements from six NHANES cycles from 2003 to 2014.

Developmental low-dose exposure to bisphenol A induces chronic inflammation, bone marrow fibrosis and reduces bone stiffness in female rat offspring only.

Background: Developmental exposure to low doses of the endocrine disruptor bisphenol A (BPA) is known to alter bone tissue in young rodents, although how bone tissue is affected in aged animals is not well known. We have recently shown that low-dose developmental exposure to BPA increases procollagen type I N-terminal propeptide (P1NP) levels, a peptide formed during type 1 collagen synthesis, in plasma of 5-week-old female rat offspring while male offspring showed reduced bone size.

Objective: To analyze offspring bone phenotype at 52 weeks of age and clarify whether the BPA-induced increase in P1NP levels at 5 weeks is an early sign of bone marrow fibrosis development.

Association of Exposure to Persistent Organic Pollutants With Mortality Risk: An Analysis of Data From the Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS) Study.

Importance: It has been suggested that persistent organic pollutants (POPs) are harmful to human health.

Objective: To investigate if POP levels in plasma are associated with future mortality.

Design, Setting, And Participants: Cohort study using data from the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, collected between May 2001 and June 2004 when participants reached age 70 years.

Developmental exposure to a very low dose of bisphenol A induces persistent islet insulin hypersecretion in Fischer 344 rat offspring.

Background: In children with obesity, accentuated insulin secretion has been coupled with development of type 2 diabetes mellitus (T2DM). Bisphenol A (BPA) is a chemical with endocrine- and metabolism-disrupting properties which can be measured in a majority of the population. Exposure to BPA has been associated with the development of metabolic diseases including T2DM.

Identification of metabolic profiles associated with human exposure to perfluoroalkyl substances.

Recent epidemiological studies suggest that human exposure to perfluoroalkyl substances (PFASs) may be associated with type 2 diabetes and other metabolic phenotypes. To gain further insights regarding PFASs exposure in humans, we here aimed to characterize the associations between different PFASs and the metabolome. In this cross-sectional study, we investigated 965 individuals from Sweden (all aged 70 years, 50% women) sampled in 2001-2004.