Person:

Weihe, Pal

Objective: Vitamin D deficiency is thought to be a risk factor for development of type 2 diabetes, and elderly subjects at northern latitudes may therefore be at particular risk. Research Design and Methods: Vitamin D status was assessed from serum concentrations of 25-hydroxyvitamin D3 [25(OH)D3] in 668 Faroese residents aged 70–74 years (64% of eligible population). We determined type 2 diabetes prevalence from past medical histories, fasting plasma concentrations of glucose, and/or glycosylated hemoglobin (HbA1c). Results: We observed 70 (11%) new type 2 diabetic subjects, whereas 88 (13%) were previously diagnosed. Having vitamin D status <50 nmol/L doubled the risk of newly diagnosed type 2 diabetes after adjustment for BMI, sex, exposure to polychlorinated biphenyls, serum triacylglyceride concentration, serum HDL concentration, smoking status, and month of blood sampling. Furthermore, the HbA1c concentration decreased at higher serum 25(OH)D3 concentrations independent of covariates. Conclusions: In elderly subjects, vitamin D sufficiency may provide protection against type 2 diabetes. Because the study is cross-sectional, intervention studies are needed to elucidate whether vitamin D could be used to prevent development of type 2 diabetes.

Passage of environmental chemicals across the placenta has important toxicological consequences, as well as for choosing samples for analysis and for interpreting the results. To obtain systematic data, we collected in 2000 maternal and cord blood, cord tissue, placenta, and milk in connection with births in the Faroe Islands, where exposures to marine contaminants is increased. In 15 sample sets, we measured a total of 87 environmental chemicals, almost all of which were detected both in maternal and fetal tissues. The maternal serum lipid-based concentrations of organohalogen compounds averaged 1.7 times those of cord serum, 2.8 times those of cord tissue and placenta, and 0.7those of milk. For organohalogen compounds detectable in all matrices, a high degree of correlation between concentrations in maternal serum and the other tissues investigated was generally observed (r 2 > 0.5). Greater degree of chlorination resulted in lower transfer from maternal serum into milk. Concentrations of pentachlorbenzene,γ-hexachlorocyclohexane, and several polychlorinated biphenyl congeners with low chlorination were higher in fetal samples and showed poor correlation with maternal levels. Perfluorinated compounds occurred in lower concentrations in cord serum than in maternal serum. Cadmium, lead, mercury, and selenium were all detected in fetal samples, but only mercury showed close correlations among concentrations in different matrices. Although the environmental chemicals examined pass through the placenta and are excreted into milk, partitions between maternal and fetal samples are not uniform.

Background: Exposure to organochlorine compounds (OCs) can alter thyroid function in humans, and hypothyroidism during early life can adversely affect a child’s neurodevelopment. Objectives: In this study we aimed to assess the relationship between developmental organochlorine exposures and thyroid function and the relationship between thyroid function and subsequent neurodevelopment. Methods: A population-based birth cohort of 182 children was followed annually up to 5.5 years of age. The assessments included OC concentrations in maternal pregnancy serum and milk, clinical thyroid parameters in maternal and cord serum, and subsequent neuropsychological outcomes of the child, along with sociodemographic cofactors. Resin triiodothyronine uptake ratio (T3RU) was also assessed as an estimate of the amount of thyroxine-binding globulin (TBG) sites unsaturated by thyroxine. The T3RU is high in hyperthyroidism and low in hypothyroidism. Results: The findings showed consistent inverse and monotonic associations between organochlorine exposure and T3RU after covariate adjustments. We observed no associations with other thyroid parameters. T3RU was positively associated with improved performance on most of the neuropsychological tests. For other thyroid parameters, the findings were less consistent. Conclusions: The results suggest that OC exposures may decrease the T3RU during early life, which is a proxy measure of the binding capacity of TBG. In addition, minor decreases of the thyroid function may be inversely associated with a child’s neurodevelopment.

Background: Some persistent environmental chemicals are suspected of causing an increased risk of type 2 diabetes mellitus, a disease particularly common after the age of 70. This concern was examined in a cross-sectional study of elderly subjects from a fishing population with elevated contaminant exposures from seafood species high in the food chain. Methods: Clinical examinations of 713 Faroese residents aged 70 –74 years (64% of eligible population) included fasting plasma concentrations of glucose and insulin, and glycosylated hemoglobin. Lifetime exposure to persistent environmental chemicals from pilot whale and other traditional food was estimated from a dietary questionnaire and by analysis of blood samples for polychlorinated biphenyls (PCBs) and related food contaminants. Results: Septuagenarians with type 2 diabetes or impaired fasting glycemia tended to have higher PCB concentrations and higher past intake of traditional foods, especially during childhood and adolescence. In nondiabetic subjects, the fasting insulin concentration decreased by 7% (95% CI 12% to 2%) for each doubling of the PCB concentration after adjustment for sex and body mass index at age 20. Conversely, the fasting glucose concentration increased by 6% (1% to 13%) for each doubling in PCB. Similar associations were seen in subjects without impaired fasting glycemia, while further adjustment for current body mass index and lipid metabolism parameters attenuated some of the associations. Conclusions: Impaired insulin secretion appears to constitute an important part of the type 2 diabetes pathogenesis associated with exposure to persistent lipophilic food contaminants.

People in the Arctic as well as fishermen on the polluted Swedish east coast are highly exposed to persistent organic pollutants (POPs). These compounds have been shown to affect the sperm Y:X chromosome ratio. In present study, the aim was to investigate whether polychlorinated biphenyl (PCB) congeners and 1,1,-dichloro-2,2,-bis(p-chlorophenyl)ethane (p,p′-DDE) influence sperm sex chromosome ratio in Faroese men, and whether these men differ regarding Y:X ratio compared to Greenland Inuit and Swedish fishermen.

The study population (n = 449) consisted of young men from the general population (n = 276) as well as proven fertile men (n = 173). The Y:X ratio was assessed by fluorescent in situ hybridization. Serum concentrations of POPs were measured using gas chromatography. Associations between POP concentrations and Y:X ratio were calculated using linear and non-linear regression models as well as trend analysis and pairwise comparison of exposure data categorized into quartiles.

The selected POPs were associated with Y:X ratio in fertile Faroese men, but not in the total population; p,p′-DDE (95% CI for B = − 0.005 to − 0.001, p = 0.005) and ΣPCB (95% CI for B = − 0.005 to − 0.001, p = 0.012). Since p,p′-DDE and ΣPCB correlated significantly (r = 0.927, p < 0.001), the results involving the exposure variables can be regarded as a single finding. The Y:X ratio for the total Faroese population was 0.500 ± 0.018, which was statistically significantly lower than in both Inuit and Swedish fishermen (0.512 for both).

In conclusion, Faroese men presented with lower Y:X ratio than Greenland Inuit and Swedish fishermen. Although no direct health effects are expected due to the lower Faroese Y:X ratio, it could be indicative of adverse effects on the reproductive system.

A prospective birth cohort of 1022 participants was established in the Faroe Islands over a 21-month period during 1986–1987. We collected questionnaire data on potential persistent organic pollutant (POP) concentration predictors, such as duration of breastfeeding and blubber consumption. To assess the participants’ exposure from in utero to 14 years of age to polychlorinated biphenyls (PCBs) and the insecticide p,p′-DDT and its primary degradate p,p′-DDE, we measured 37 PCB congeners and pesticides in 316 umbilical cord samples taken from participants at birth, in 124 serum samples collected from participants at approximately 7 years of age, and in 795 serum samples collected from participants at 14 years of age. Measurements of higher chlorination PCB congeners made on individuals’ serum samples collected at 7 years and 14 years were highly correlated (typically r > 0.5, p > 0.01), although their concentrations at 7 years were generally two to three times higher than at 14 years. Similarly, umbilical cord PCB concentrations were correlated with PCB concentrations in both 7- and 14-year serum samples. Sex-specific differences in higher chlorination PCB and p,p′-DDE concentrations were found at 14 years but not at 7 years, although a sex interaction with blubber consumption and nursing duration was observed at both ages. Both duration of breastfeeding and consumption of blubber were significant predictors of serum ∑ PCB concentrations at 7 and 14 years. Multivariate analyses showed that breastfeeding duration was the primary contributor to serum ∑ PCB concentrations at 7 years, and blubber consumption was the primary contributor at 14 years. These data suggest that infant exposures from breastfeeding were sufficiently large so that continued exposures to PCBs, p,p′-DDT, and p,p′-DDE through the diet have not fully diluted their contribution to the ∑ PCB and p,p′-DDE body burden of the children.

The objective of this study was to assess blood concentrations of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs), and their polychlorobiphenylol (OH-PCB) metabolites in humans with a high seafood intake. Samples were obtained from pregnant women in the Faroe Islands in 1994−1995 and from their children at 7 years of age to examine maternal transfer of the compounds to their child, age-dependent metabolism, and temporal changes. Maternal serum was dominated by 2,2‘,4,4‘-tetrabromodiphenyl ether (BDE-47), while 2,2‘,4,4‘,5,5‘-hexabromodiphenyl ether (BDE-153) prevailed in the children's serum seven years later. DecaBDE was present in both mothers and children up to 3 and 6 ng/g lipid weight, respectively. The ΣPCB concentration in the children averaged about 60% of the concentrations in their mothers, with median levels for both above 1 μg/g lipid weight and with similar PCB congener patterns. ΣOH-PCB serum concentrations from the mothers and their children showed ranges of 1.8−36 ng/g wet weight (ww) and 0.49−22 ng/g ww, respectively, with all OH-PCB congener concentrations being lower in the children, except for 2,3,3‘,4‘,5-pentachloro-4-biphenylol (4-OH-CB107). Children at 7 years of age are exposed to PCBs at levels only slightly below those of their mothers, and the increased 4-OH-CB107 concentrations in children could be due to age-related differences in PCB metabolism. The PBDE concentrations were similar in both mothers and their children. The main persistent organic pollutant concentrations in the children are most probably due to other environmental exposure than maternal transfer.

Background: Epidemiological documentation of endocrine disruption is complicated by imprecise exposure assessment, especially when exposures are mixed. Even if the estrogenic activity of all compounds were known, the combined effect of possible additive and/or inhibiting interaction of xenoestrogens in a biological sample may be difficult to predict from chemical analysis of single compounds alone. Thus, analysis of mixtures allows evaluation of combined effects of chemicals each present at low concentrations. Methods: We have developed an optimized in vitro E-Screen test to assess the combined functional estrogenic response of human serum. The xenoestrogens in serum were separated from endogenous steroids and pharmaceuticals by solid-phase extraction followed by fractionation by high-performance liquid chromatography. After dissolution of the isolated fraction in ethanol-DMSO, the reconstituted extract was added with estrogen-depleted fetal calf serum to MCF-7 cells, the growth of which is stimulated by estrogen. After a 6-day incubation on a microwell plate, cell proliferation was assessed and compared with the effect of a 17-beta-estradiol standard. Results: and conclusions To determine the applicability of this approach, we assessed the estrogenicity of serum samples from 30 pregnant and 60 non-pregnant Danish women thought to be exposed only to low levels of endocrine disruptors. We also studied 211 serum samples from pregnant Faroese women, whose marine diet included whale blubber that contain a high concentration of persistent halogenated pollutants. The estrogenicity of the serum from Danish controls exceeded the background in 22.7 % of the cases, while the same was true for 68.1 % of the Faroese samples. The increased estrogenicity response did not correlate with the lipid-based concentrations of individual suspected endocrine disruptors in the Faroese samples. When added along with the estradiol standard, an indication of an enhanced estrogenic response was found in most cases. Thus, the in vitro estrogenicity response offers a promising and feasible approach for an aggregated exposure assessment for xenoestrogens in serum.

Background: Fish and seafood provide important nutrients but may also contain toxic contaminants, such as methylmercury. Advisories against pollutants may therefore conflict with dietary recommendations. In resolving this conundrum, most epidemiologic studies provide little guidance because they address either nutrient benefits or mercury toxicity, not both. Objectives: Impact on the same health outcomes by two exposures originating from the same food source provides a classical example of confounding. To explore the extent of this bias, we applied structural equation modeling to data from a prospective study of developmental methylmercury neurotoxicity in the Faroe Islands. Results: Adjustment for the benefits conferred by maternal fish intake during pregnancy resulted in an increased effect of the prenatal methylmercury exposure, as compared with the unadjusted results. The dietary questionnaire response is likely to be an imprecise proxy for the transfer of seafood nutrients to the fetus, and this imprecision may bias the confounder-adjusted mercury effect estimate. We explored the magnitude of this bias in sensitivity analysis assuming a range of error variances. At realistic imprecision levels, mercury-associated deficits increased by up to 2-fold when compared with the unadjusted effects. Conclusions: These results suggest that uncontrolled confounding from a beneficial parameter, and imprecision of this confounder, may cause substantial underestimation of the effects of a toxic exposure. The adverse effects of methylmercury exposure from fish and seafood are therefore likely to be underestimated by unadjusted results from observational studies, and the extent of this bias will be study dependent.

Background: Methylmercury (MeHg), a worldwide contaminant found in fish and seafood, has been linked to an increased risk of cardiovascular mortality. Objective: We examined 42 Faroese whaling men (30–70 years of age) to assess possible adverse effects within a wide range of MeHg exposures from consumption of pilot whale meat. Methods: We assessed exposure levels from mercury analysis of toenails and whole blood (obtained at the time of clinical examination), and a hair sample collected 7 years previously. Outcome measures included heart rate variability (HRV), blood pressure (BP), common carotid intima-media thickness (IMT), and brainstem auditory evoked potentials (BAEP). We carried out multiple regression and structural equation model (SEM) analyses to determine the confounder-adjusted effect of mercury exposure. Taking into account correlations among related measures, we categorized exposure and outcomes in groups to derive latent exposure and response variables in SEMs. We used multiple regression analysis to compare the predictive validity of individual exposure biomarkers and the latent exposure variable on individual and latent outcomes. Results: The toenail mercury concentrations varied widely and had a geometric mean of 2.0 μg/g; hair concentrations averaged about 3-fold higher. Mercury exposure was significantly associated with increased BP and IMT. This effect was reflected by SEMs, but mercury in toenails tended to be the best effect predictor. Conclusions: The results support the notion that increased MeHg exposure promotes the development of cardiovascular disease.