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Background: The incidence of the insulin resistance syndrome has increased at an alarming rate worldwide, creating a serious challenge to public health care in the 21st century. Recently, epidemiological studies have associated the prevalence of type 2 diabetes with elevated body burdens of persistent organic pollutants (POPs). However, experimental evidence demonstrating a causal link between POPs and the development of insulin resistance is lacking.

Objective: We investigated whether exposure to POPs contributes to insulin resistance and metabolic disorders.

Methods: Sprague-Dawley rats were exposed for 28 days to lipophilic POPs through the consumption of a high-fat diet containing either refined or crude fish oil obtained from farmed Atlantic salmon. In addition, differentiated adipocytes were exposed to several POP mixtures that mimicked the relative abundance of organic pollutants present in crude salmon oil. We measured body weight, whole-body insulin sensitivity, POP accumulation, lipid and glucose homeostasis, and gene expression and we performed microarray analysis.

Results: Adult male rats exposed to crude, but not refined, salmon oil developed insulin resistance, abdominal obesity, and hepatosteatosis. The contribution of POPs to insulin resistance was confirmed in cultured adipocytes where POPs, especially organochlorine pesticides, led to robust inhibition of insulin action. Moreover, POPs induced down-regulation of insulin-induced gene-1 (Insig-1) and Lpin1, two master regulators of lipid homeostasis.

Conclusion: Our findings provide evidence that exposure to POPs commonly present in food chains leads to insulin resistance and associated metabolic disorders.

Background: Cross-sectional and ecological studies indicate that air pollution may be a risk factor for type 2 diabetes, but prospective data are lacking.

Objective: We examined the association between traffic-related air pollution and incident type 2 diabetes.

Design: Between 1985 and 1994, cross-sectional surveys were performed in the highly industrialized Ruhr district (West Germany); a follow-up investigation was conducted in 2006 using data from the Study on the Influence of Air Pollution on Lung, Inflammation and Aging (SALIA) cohort.

Participants: 1,775 nondiabetic women who were 54–55 years old at baseline participated in both baseline and follow-up investigations and had complete information available.

Materials and Methods: Using questionnaires, we assessed 16-year incidence (1990–2006) of type 2 diabetes and information about covariates. Complement factor C3c as marker for subclinical inflammation was measured at baseline. Individual exposure to traffic-related particulate matter (PM) and nitrogen dioxide was determined at different spatial scales.

Results: Between 1990 and 2006, 87 (10.5%) new cases of diabetes were reported among the SALIA cohort members. The hazards for diabetes were increased by 15–42% per interquartile range of PM or traffic-related exposure. The associations persisted when different spatial scales were used to assess exposure and remained robust after adjusting for age, body mass index, socioeconomic status, and exposure to several non–traffic-related sources of air pollution. C3c was associated with PM pollution at baseline and was a strong independent predictor of incident diabetes. Exploratory analyses indicated that women with high C3c blood levels were more susceptible for PM-related excess risk of diabetes than were women with low C3c levels.

Conclusions: Traffic-related air pollution is associated with incident type 2 diabetes among elderly women. Subclinical inflammation may be a mechanism linking air pollution with type 2 diabetes.

Relevance to clinical practice: Our study identifies traffic-related air pollution as a novel and potentially modifiable risk factor of type 2 diabetes.

Background: Prospective data regarding persistent organic pollutants (POPs) and risk of type 2 diabetes (T2D) are limited, and the results for individual POPs are not entirely consistent across studies.

Objectives: We prospectively examined plasma POP concentrations in relation to incident T2D and summarized existing evidence in a meta-analysis.

Methods: Plasma polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and hexachlorobenzene (HCB) concentrations were measured in 1,095 women who were free of diabetes at blood draw in 1989–1990 and participated in two case–control studies in the Nurses’ Health Study. We identified 48 incident T2D cases through 30 June 2008. We conducted a literature search in PubMed and EMBASE through December 2011 to identify prospective studies on POPs in relation to diabetes. We used a fixed-effects model to summarize results.

Results: After multivariable adjustment, plasma HCB concentration was positively associated with incident T2D [pooled odds ratio (OR) 3.59 (95% CI: 1.49, 8.64, p_trend = 0.003) comparing extreme tertiles]. Other POPs were not significantly associated with diabetes. After pooling our results with those of six published prospective studies that included 842 diabetes cases in total, we found that HCB and total PCBs both were associated with diabetes: the pooled ORs were 2.00 (95% CI: 1.13, 3.53; I = 21.4%, p_{heterogeneity} = 0.28) and 1.70 (95% CI: 1.28, 2.27; I = 16.3%, p_{heterogeneity} = 0.30) for HCB and total PCBs, respectively.

Conclusions: These findings support an association between POP exposure and the risk of T2D.

Background: There is growing evidence that chronic exposure to inorganic arsenic (iAs) is associated with an increased prevalence of type 2 diabetes (T2D). However, the mechanisms for the diabetogenic effect of iAs are still largely unknown. White adipose tissue (WAT) actively stores and releases energy and maintains lipid and glucose homeostasis.

Objective: We sought to determine the mechanisms of arsenic suppression of adipogenesis.

Methods: The effects and associated mechanisms of iAs and its major metabolites on adipogenesis were determined in 3T3-L1 preadipocytes, mouse adipose-derived stromal-vascular fraction cells (ADSVFCs), and human adipose tissue–derived stem cells (ADSCs).

Results: Exposure of 3T3-L1 preadipocytes to noncytotoxic levels of arsenic, including inorganic arsenite (iAs, ≤ 5 μM), inorganic arsenate (≤ 20 μM), trivalent monomethylated arsenic (MMA, ≤ 1 μM), and trivalent dimethylated arsenic (DMA, ≤ 2 μM) decreased adipogenic hormone-induced adipogenesis in a concentration-dependent manner. In addition, iAs, MMA, and DMA exhibited a strong inhibitory effect on adipogenesis in primary cultured mouse ADSVFCs and human ADSCs. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by arsenic occurred in the early stage of terminal adipogenic differentiation and was highly correlated with the induction of C/EBP homologous protein (CHOP10), an endoplasmic reticulum (ER) stress response protein. Induction of CHOP10 by arsenic is associated with reduced DNA-binding activity of CCAAT/enhancer-binding protein β (C/EBPβ), which regulates the transcription of peroxisome proliferator-activated receptor γ and C/EBPα.

Conclusions: Low-level iAs and MMA trigger the ER stress response and up-regulate CHOP10, which inhibits C/EBPβ transcriptional activity, thus suppressing adipogenesis. Arsenic-induced dysfunctional adipogenesis may be associated with a reduced capacity of WAT to store lipids and with insulin resistance.