A computational approach to chemical etiologies of diabetes.

Computational meta-analysis can link environmental chemicals to genes and proteins involved in human diseases, thereby elucidating possible etiologies and pathogeneses of non-communicable diseases. We used an integrated computational systems biology approach to examine possible pathogenetic linkages in type 2 diabetes (T2D) through genome-wide associations, disease similarities, and published empirical evidence. Ten environmental chemicals were found to be potentially linked to T2D, the highest scores were observed for arsenic, 2,3,7,8-tetrachlorodibenzo-p-dioxin, hexachlorobenzene, and perfluorooctanoic acid. For these substances we integrated disease and pathway annotations on top of protein interactions to reveal possible pathogenetic pathways that deserve empirical testing. The approach is general and can address other public health concerns in addition to identifying diabetogenic chemicals, and offers thus promising guidance for future research in regard to the etiology and pathogenesis of complex diseases

Exposure to p,p′-DDE: A Risk Factor for Type 2 Diabetes

BACKGROUND: Persistent organic pollutants (POPs), such as PCBs, DDT and dioxins have in several cross-sectional studies shown strong associations with type 2 diabetes mellitus. Reversed causality can however not be excluded. The aim of this case-control study was to evaluate whether POPs concentration is a risk factor for type 2 diabetes. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study was performed within a well-defined cohort of women, age 50-59 years, from the Southern part of Sweden. Biomarkers for POP exposure, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were analyzed in stored serum samples, which were collected at the baseline examination when the cohort was established. For 107 out of the 371 cases, serum samples were stored at least three years before their type 2 diabetes was diagnosed. In this data set, CB-153 and p,p'-DDE were not associated with an increased risk to develop type 2 diabetes. However, when only the cases (n = 39) that were diagnosed more than six years after the baseline examination and their controls were studied, the women in the highest exposed quartile showed an increased risk to develop type 2 diabetes (OR of 1.6 [95% 0.61, 4.0] for CB-153 and 5.5 [95% CI 1.2, 25] for p,p'-DDE). CONCLUSIONS/SIGNIFICANCE: The results from the present case-control study, including a follow-up design, confirms that p,p'-DDE exposure can be a risk factor for type 2 diabetes

An Environment-Wide Association Study (EWAS) on Type 2 Diabetes Mellitus

Background: Type 2 Diabetes (T2D) and other chronic diseases are caused by a complex combination of many genetic and environmental factors. Few methods are available to comprehensively associate specific physical environmental factors with disease. We conducted a pilot Environmental-Wide Association Study (EWAS), in which epidemiological data are comprehensively and systematically interpreted in a manner analogous to a Genome Wide Association Study (GWAS). Methods and Findings: We performed multiple cross-sectional analyses associating 266 unique environmental factors with clinical status for T2D defined by fasting blood sugar (FBG) concentration $126 mg/dL. We utilized available Centers for Disease Control (CDC) National Health and Nutrition Examination Survey (NHANES) cohorts from years 1999 to 2006. Within cohort sample numbers ranged from 503 to 3,318. Logistic regression models were adjusted for age, sex, body mass index (BMI), ethnicity, and an estimate of socioeconomic status (SES). As in GWAS, multiple comparisons were controlled and significant findings were validated with other cohorts. We discovered significant associations for the pesticide-derivative heptachlor epoxide (adjusted OR in three combined cohorts of 1.7 for a 1 SD change in exposure amount; p,0.001), and the vitamin c-tocopherol (adjusted OR 1.5; p,0.001). Higher concentrations of polychlorinated biphenyls (PCBs) such as PCB170 (adjusted OR 2.2; p,0.001) were also found. Protective factors associated with T2D included b-carotenes (adjusted OR 0.6; p,0.001)

Environmental reproductive justice: intersections in an American Indian community impacted by environmental contamination

In order to fully understand the impact of contamination on Indigenous communities, this paper explores how intersectionality has been integral to the development of environmental justice (EJ) and reproductive justice (RJ), and how considering the ways in which these two frameworks then intersect with each other is necessary to more fully explicate how toxicants have threatened the reproduction of human beings and tribal culture. The concept of environmental reproductive justice (ERJ), or ensuring that environmental issues do not interfere with physical or cultural reproduction, involves expanding reproductive justice to include a deeper focus on the environment, and to include the reproduction of language and culture as concerns, in addition to the reproduction of human beings. ERJ also aims to expand the framework of environmental justice to more closely consider the impact of environmental contaminants on physical and cultural reproduction. Through the example of Akwesasne, a Mohawk American Indian community located downstream from industrial sites on the New York/Canadian border, this paper explores how the concept of ERJ can be utilized to understand the unique situation of American Indian communities who are arguing that justice necessitates going beyond equal protection