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Glukosu metabolisma og immunverja hjá vaksnum fólki, sum hava verið fyri dálkingarevnum í móðurlívi.


Pál Weihe

Deildin fyri Arbeiðs- og Almannaheilsu

Aðrir luttakarar:
Jónrit Halling, Phillipe Grandjean, Carsten Heilman, Flemming Nielsen, Anna Choi, Karsten Kristiansen, Frank B. Hu, Shuk Mei Ho og Kurt Højlund


Samlaður kostnaður:
5.743.896 DKK

Stuðul úr Granskingargrunninum:
850.000 DKK

Since 1986 we have followed a cohort of 1,022 births generated from consecutive births at the three Faroese hospitals during 1986-1987. At age 7 years, 90% of cohort subjects underwent a clinical examination, 87% at age 14 and 84% at age 22. At all ages blood samples was drawn for mercury and PCB analyses. This cohort will now be invited to participate in two project taking place at the same time.

In the first project (Glucose Metabolism in Adults Prenatally Exposed to Diabetogenic Pollutants)all the cohort members will be invited, but in the second project (Immunotoxicity in Humans with Lifetime Exposure to Ocean Pollutants) only 250 will be requested to participate.

Glucose Metabolism in Adults Prenatally Exposed to Diabetogenic Pollutants:

Type 2 diabetes (T2D) is a major public health problem, which continues to grow. A total of 25.8 million Americans have diabetes, 7 million of them being undiagnosed, while 79 million adults above 20 years of age have prediabetes (impaired fasting glucose, IFG). T2D is a chronic disease that increases mortality and morbidity due to a variety of complications.

Mounting evidence now suggests environmental chemicals somehow stimulate the development of obesity, T2D, and the metabolic syndrome. Thus, a growing number of epidemiology studies, supported by results from experimental models, suggest that certain persistent organic pollutants (POPs) can contribute to the development of T2D. Our hypothesis is that T2D development may occur as a result of a combination of insulin insensitivity, beta-cell stress, and obesity, and that these changes will be apparent in young adults as a result of POP exposures during prenatal programming and during postnatal development. The overall goal of the proposed project is therefore to examine assess whether developmental (prenatal) exposure to environmental chemicals may be associated with the development of altered glucose metabolism, decreased insulin sensitivity, metabolic inflexibility, and early clinical signs of metabolic syndrome development by age 28 years. We also hypothesize that epigenetic alteration is an important mechanism by which developmental exposure to POPs contribute to the etiology of glucose metabolism dysfunctions. We will focus on persistent organochlorine and perfluorinated substances as the most likely culprits.

Specific aim 1: To determine if prenatal and/or postnatal exposure to persistent organochlorine and/or perfluorinated compounds is associated with signs of impaired glucose metabolism at age 27 years.

Specific aim 2: To assess similarly the possible impact of exposures to the environmental chemicals on subsequent changes in body weight and its possible modulating effect on the risk of subsequent development of impaired glucose metabolism.

Specific aim 3: We will examine the cross-sectional and temporal associations of epigenetic markers with developmental exposures to POPs and indicators of impaired glucose metabolism at age 28, and we will examine if the epigenetic alterations can explain any associations between developmental POP exposures with the development of impaired glucose metabolism.

As a secondary aim, we will assess dietary and lifestyle determinants of increased exposure to persistent organochlorine and/or perfluorinated compounds and their possible impact on exposure-associated risks of impaired glucose metabolism and weight changes. We will also assess any modifying effects of other risk indicators, such as physical activity, on the POP-associated risks.

Immunotoxicity in Humans with Lifetime Exposure to Ocean Pollutants:

Immunotoxicity has been identified as a serious potential hazard associated with ocean pollutant exposures in marine mammal. Much of this evidence is based on cross-sectional studies and outcome parameters of uncertain validity and is therefore not directly applicable to human health risk assessment. This project will aim at placing appropriate emphasis on immunotoxic effects that may occur in humans exposed to the same ocean pollutants via marine food.

Human exposures to ocean pollutants depend on dietary habits and the degree of seafood contamination. Exposures of the greatest current concern include priority contaminants, such as methylmercury and PCBs. Our recent research suggests adding the perfluorinated compounds (PFCs) on the list of ocean pollutants as a human health concern. The highest dietary exposures to PFCs occur in northern populations relying on seafood, especially if including marine mammals.

Specific aim 1: Do both prenatal and early postnatal exposures to ocean pollutants contribute to immune response deficiencies in childhood, and are these lasting effects.

Specific aim 2: Do life-time exposures to immunotoxic pollutants affect responses to new antigens also in adulthood?

Specific aim 3: Do exposures to immunotoxic ocean pollutants also affect the occurrence of allergic diseases and atopy.

Specific aim 4: Which immunotoxicants are responsible for these effects, what are their sources, and at which exposure levels do they cause harmful effects?

The need for research in this field is supported by several prospective studies of children exposed to suspected immunotoxicants. The adverse effects on the prevalence of allergic diseases, incidence of infectious disease, and/or concentrations of immunoglobulins in serum have been reported. However, the studies are not systematic and often lack important information, such as the time interval since last immunization, or immunotoxicant exposure during vulnerable time windows. Allergic diseases in children appear to be increasingly common, as suggested by international evidence.

We will use detailed dietary intake data and exposure biomarkers to estimate the impact of different seafood sources and the changes in concentrations in ocean harvesting regions. The Faroese exposures can be linked almost exclusively to locally harvested fish and marine mammal populations, thus allowing us to directly link their exposures to changing emissions and accumulation in ocean ecosystems, especially for mercury and the PFCs. The relative contribution of branched PFC isomers will provide crucial input to the calculations of possible source attributions, not previously attempted in regard to seafood.

The cohort members will be invited for examinations at age 28 years in 2013-2015 to assess antibody concentrations and to conduct a vaccination trial. We will aim at including 250 cohort members. Cord blood is available for all subjects, and we will aim at including subjects who also participated in the age-7 examinations (90%) and from whom banked serum is available for the proposed antibody and PFC analyses.


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