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Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up.

ABSTRACT: Substantial evidence associates persistent organic pollutants (POP) with metabolic disturbances related to diabetes, but longitudinal studies with repeated measures are scarce. We aimed to characterize the association between background exposures to POPs with repeated measures of glucose homeostasis over 23-years.Within the Coronary Artery Risk Development in Young Adults study (year 0 ages: 18-30 years), we measured POPs in serum obtained in 1987-88 (follow-up year 2) in 90 non-diabetic controls and 90 cases diabetes-free at year 2 who became diabetic by year 20. We analyzed 32 POPs detectable in ?75% of participants and created summary scores for 32 POPs, 23 polychlorinated biphenyls (PCB), and 8 organochlorine pesticides (OCP). Dependent variables were measures of glucose homeostasis at years 0-25 (up to 8 examinations). We explored associations using repeated measures regression adjusted for race, sex, concurrent body mass index (BMI), examination center and period, separately for cases and controls.The associations between the three summary scores and measures of glucose homeostasis were present for observations at ages 40-55 years, and particularly between 48-55 years: the 23 PCB summary was associated with HbA1c (never-diabetics: slope [value per unit of summary score], ?=0.008, p=0.02; diabetics: ?=0.03, p=0.07), fasting glucose (never-diabetics: ?=0.24, p=0.003; diabetics: ?=1.10, p=0.03), and insulin sensitivity% (never-diabetics: ?=-2.82, p<0.001, diabetics: ?=-0.31, p=0.30). No associations were observed at younger ages.Glucose homeostasis may worsen after decades of exposure to PCBs and OCPs at background environmental levels, independent of BMI and after participants reached the 5th decade of life.

SUBMITTER: Suarez-Lopez JR

PROVIDER: S-EPMC4429782 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up.

Suarez-Lopez Jose R JR Lee Duk-Hee DH Porta Miquel M Steffes Michael W MW Jacobs David R DR

Environmental research 20150223

<h4>Objectives</h4>Substantial evidence associates persistent organic pollutants (POP) with metabolic disturbances related to diabetes, but longitudinal studies with repeated measures are scarce. We aimed to characterize the association between background exposures to POPs with repeated measures of glucose homeostasis over 23-years.<h4>Methods</h4>Within the Coronary Artery Risk Development in Young Adults study (year 0 ages: 18-30 years), we measured POPs in serum obtained in 1987-88 (follow-up ...[more]

PMID: 25706918

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Project description:Exposure to persistent organic pollutants (POPs), such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs), has historically been linked to population collapses in wildlife. Despite international regulations, these legacy chemicals are still currently detected in women of reproductive age, and their levels correlate with reduced ovarian reserve, longer time-to-pregnancy, and higher risk of infertility. However, the specific modes of action underlying these associations remain unclear. Here, we examined the effects of five commonly occurring POPs − hexachlorobenzene (HCB), p,p'-dichlorodiphenyldichloroethylene (DDE), 2,3,3′,4,4′,5-hexachlorobiphenyl (PCB156), 2,2′,3,4,4′,5,5′-heptachlorobiphenyl (PCB180), perfluorooctane sulfonate (PFOS) − and their mixture on human ovaries in vitro. We exposed human ovarian cancer cell lines COV434, KGN, and PA1 as well as primary ovarian cells for 24 h, and ovarian tissue containing unilaminar follicles for 6 days. RNA-sequencing of samples exposed to concentrations covering epidemiologically relevant levels revealed significant gene expression changes related to central energy metabolism in the exposed cells, indicating glycolysis, oxidative phosphorylation, fatty acid metabolism, and reactive oxygen species as potential shared targets of POP exposures in ovarian cells. Alpha-enolase (ENO1), lactate dehydrogenase A (LDHA), cytochrome C oxidase subunit 4I1 (COX4I1), ATP synthase F1 subunit alpha (ATP5A), and glutathione peroxidase 4 (GPX4) were validated as targets through qPCR in additional cell culture experiments in KGN. In ovarian tissue cultures, we observed significant effects of exposure on follicle growth and atresia as well as protein expression. All POP exposures, except PCB180, decreased unilaminar follicle proportion and increased follicle atresia. Immunostaining confirmed altered expression of LDHA, ATP5A, and GPX4 in the exposed tissues. Moreover, POP exposures modified ATP production in KGN and tissue culture. In conclusion, our results demonstrate the disruption of cellular energy metabolism as a novel mode of action underlying POP-mediated interference of follicle growth in human ovaries.

Project description:ObjectiveTo examine the association between alcohol consumption and risk of dementia.DesignProspective cohort study.SettingCivil service departments in London (Whitehall II study).Participants9087 participants aged 35-55 years at study inception (1985/88).Main outcome measuresIncident dementia, identified through linkage to hospital, mental health services, and mortality registers until 2017. Measures of alcohol consumption were the mean from three assessments between 1985/88 and 1991/93 (midlife), categorised as abstinence, 1-14 units/week, and >14 units/week; 17 year trajectories of alcohol consumption based on five assessments of alcohol consumption between 1985/88 and 2002/04; CAGE questionnaire for alcohol dependence assessed in 1991/93; and hospital admission for alcohol related chronic diseases between 1991 and 2017.Results397 cases of dementia were recorded over a mean follow-up of 23 years. Abstinence in midlife was associated with a higher risk of dementia (hazard ratio 1.47, 95% confidence interval 1.15 to 1.89) compared with consumption of 1-14 units/week. Among those drinking >14 units/week, a 7 unit increase in alcohol consumption was associated with a 17% (95% confidence interval 4% to 32%) increase in risk of dementia. CAGE score >2 (hazard ratio 2.19, 1.29 to 3.71) and alcohol related hospital admission (4.28, 2.72 to 6.73) were also associated with an increased risk of dementia. Alcohol consumption trajectories from midlife to early old age showed long term abstinence (1.74, 1.31 to 2.30), decrease in consumption (1.55, 1.08 to 2.22), and long term consumption >14 units/week (1.40, 1.02 to 1.93) to be associated with a higher risk of dementia compared with long term consumption of 1-14 units/week. Analysis using multistate models suggested that the excess risk of dementia associated with abstinence in midlife was partly explained by cardiometabolic disease over the follow-up as the hazard ratio of dementia in abstainers without cardiometabolic disease was 1.33 (0.88 to 2.02) compared with 1.47 (1.15 to 1.89) in the entire population.ConclusionThe risk of dementia was increased in people who abstained from alcohol in midlife or consumed >14 units/week. In several countries, guidelines define thresholds for harmful alcohol consumption much higher than 14 units/week. The present findings encourage the downward revision of such guidelines to promote cognitive health at older ages.

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Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up.

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Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up.

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