Environmental lead exposure has been linked with reduced kidney function. However, evidence about its role in diabetic kidney damage, especially when considering the nutritional status of vitamin D, is sparse. In this observational study, we investigated the association between low-level lead exposure and urinary albumin-to-creatinine ratio (UACR) and assessed potential impact of vitamin D among 4033 diabetic patients in Shanghai, China. Whole blood lead was measured by graphite furnace atomic absorption spectrometry. Serum 25-hydroxyvitamin D [25(OH)D] was tested using a chemiluminescence immunoassay. The associations of blood lead with UACR and albuminuria, defined as UACR ≥30 mg/g, according to 25(OH)D levels were analyzed using linear and Poisson regression models. A doubling of blood lead level was associated with a 10.7% higher UACR (95% CI, 6.19%–15.5%) in diabetic patients with 25(OH)D < 50 nmol/L, whereas the association was attenuated toward null (2.03%; 95% CI, −5.18% to 9.78%) in those with 25(OH)D ≥ 50 nmol/L. Similarly, the risk ratios of prevalent albuminuria per doubling of blood lead level between the two groups were 1.09 (95% CI, 1.03–1.15) and 0.99 (95% CI, 0.86–1.14), respectively. Joint analysis demonstrated that a combination of high blood lead and low 25(OH)D corresponded to significantly higher UACR. Among diabetic patients with 25(OH)D < 50 nmol/L, the increment of UACR relative to blood lead was more remarkable in those with reduced estimated glomerular filtration rate (<60 mL/min/1.73 m²). These results suggested that higher blood lead levels were associated with increased urinary albumin excretion in diabetic patients with vitamin D deficiency. Further prospective studies are needed to validate our findings and to determine whether vitamin D supplementation yields a benefit.

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental contaminant previously found in consumer surfactants and industrial fire-fighting foams. PFOS has been widely implicated in metabolic dysfunction across the lifespan, including diabetes and obesity. However, the contributions of the embryonic environment to metabolic disease remain uncharacterized. This study seeks to identify perturbations in embryonic metabolism, pancreas development, and adiposity due to developmental and subchronic PFOS exposures and their persistence into later larval and juvenile periods. Zebrafish embryos were exposed to 16 or 32 μM PFOS developmentally (1–5 days post fertilization; dpf) or subchronically (1–15 dpf). Embryonic fatty acid and macronutrient concentrations and expression of peroxisome proliferator-activated receptor (PPAR) isoforms were quantified in embryos. Pancreatic islet morphometry was assessed at 15 and 30 dpf, and adiposity and fish behavior were assessed at 15 dpf. Concentrations of lauric (C12:0) and myristic (C14:0) saturated fatty acids were increased by PFOS at 4 dpf, and PPAR gene expression was reduced. Incidence of aberrant islet morphologies, principal islet areas, and adiposity were increased in 15 dpf larvae and 30 dpf juvenile fish. Together, these data suggest that the embryonic period is a susceptible window of metabolic programming in response to PFOS exposures, and that these early exposures alone can have persisting effects later in the lifecourse.

Data (N = 10644) for US adults aged ≥20 years for 2003–2016 from National Health and Nutrition Examination Survey were analyzed to evaluate the impact of co-occurrence of obesity with diabetes, anemia, albuminuria, and hypertension on concentrations of five perfluoroalkyl acids (PFAA), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). For the total population, males, and females, co-occurrence of obesity with hypertension, albuminuria, anemia, and diabetes was found to be associated with lower adjusted geometric means (AGM) than nonobese for every PFAA. For example for females, for PFOS, AGMs for obese with no diseases, hypertension, albuminuria, anemia, and diabetes were 8.2, 10.8, 5.8, 4.6, and 7.7 ng/mL respectively. In comparison, for PFOS, for nonobese females, AGMs for those with no diseases, hypertension, albuminuria, anemia, and diabetes were found to be 8.9, 13.4, 7.7, 6.0, and 10.2 ng/mL respectively. This implies obesity is associated with higher excretion rates. Females, in general, had lower AGMs than males for both obese and nonobese for every PFAA for every disease group. For example, percent ratios of obese females to males AGMs for PFOA were 66.7%, 87.1%, 88.2%, 70.6%, and 90% for those with no diseases, hypertension, albuminuria, anemia, and diabetes respectively. The ratios of obese to nonobese AGMs for females were lower than males for every PFAA for those with no diseases and hypertension only. For example, for PFOA for those with no diseases, obese to nonobese AGM ratios were 87% for females and 100% for males. Thus, additional excretion of certain PFAAs due to obesity is higher in females than males for those with no diseases and hypertension only.

A limited but emerging body of evidence is suggestive for a beneficial association between contact with green spaces and glucose homeostasis in adults; however, such an evidence for children is scarce. We evaluated the association between time spent in green spaces and fasting blood glucose (FBG) levels and impaired fasting glucose (IFG, FBG≥110 mg/dL) in a population-based multicentric sample of 3844 Iranian schoolchildren aged 7–18 years (2015). Participants were instructed to report the average hours per week spent in green spaces separately during each season and in each type of green space (parks, woods/other natural green spaces, and private gardens/agricultural field) for a 12-month period preceding the interview. We developed linear and logistic mixed effects models with centre as random effect to evaluate the association of time spent in green spaces (separately for each type as well as all types together) with FBG and IFG, respectively, controlled for a wide range of covariates including household indicators of socioeconomic status. We observed inverse associations between time spent in green spaces, especially in natural green spaces, and FBG levels. Specifically, 1.83 h increase in the total time spent in green spaces was associated with −0.5 mg/dl (95% confidence intervals: −0.9, −0.1) change in FBG levels. We also observed reduced risk of IFG associated with time spent in green spaces; however, the association was statistically significant only for the time spent in natural green spaces. There were suggestions for stronger associations for those residing in urban areas and those from lower socioeconomic status groups; however, the interaction terms for socioeconomic status and urbanity were not statistically significant. Further longitudinal studies are required to replicate our findings in other settings with different climates and population susceptibilities.

The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.

Inorganic arsenic exposure may be associated with diabetes, but the evidence at low-moderate levels is not sufficient. Polymorphisms in diabetes-related genes have been involved in diabetes risk. We evaluated the association of inorganic arsenic exposure on diabetes in the Hortega Study, a representative sample of a general population from Valladolid, Spain. Total urine arsenic was measured in 1451 adults. Urine arsenic speciation was available in 295 randomly selected participants. To account for the confounding introduced by non-toxic seafood arsenicals, we designed a multiple imputation model to predict the missing arsenobetaine levels. The prevalence of diabetes was 8.3%. The geometric mean of total arsenic was 66.0 μg/g. The adjusted odds ratios (95% confidence interval) for diabetes comparing the highest with the lowest tertile of total arsenic were 1.76 (1.01, 3.09) and 2.14 (1.47, 3.11) before and after arsenobetaine adjustment, respectively. Polymorphisms in several genes including IL8RA, TXN, NR3C2, COX5A and GCLC showed suggestive differential associations of urine total arsenic with diabetes. The findings support the role of arsenic on diabetes and the importance of controlling for seafood arsenicals in populations with high seafood intake. Suggestive arsenic-gene interactions require confirmation in larger studies.

Ambient air pollution ranks high among the risk factors that increase the global burden of disease. Previous studies focused on assessing mortality risk and were sparsely performed in populous developing countries with deteriorating environments. We conducted a time-series study to evaluate the air pollution-associated years of life lost (YLL) and mortality risk and to identify potential modifiers relating to the season and demographic characteristics. Using linear (for YLL) and Poisson (for mortality) regression models and controlling for time-varying factors, we found that an interquartile range (IQR) increase in a three-day average cumulative (lag 0–2 day) concentrations of PM2.5, PM10, NO2 and SO2 corresponded to increases in YLL of 12.09 (95% confidence interval [CI]: 2.98–21.20), 13.69 (95% CI: 3.32–24.07), 26.95 (95% CI: 13.99–39.91) and 24.39 (95% CI: 8.62–40.15) years, respectively, and to percent increases in mortality of 1.34% (95% CI: 0.67–2.01%), 1.56% (95% CI: 0.80–2.33%), 3.36% (95% CI: 2.39–4.33%) and 2.39% (95% CI: 1.24–3.55%), respectively. Among the specific causes of death, cardiovascular and respiratory diseases were positively associated with gaseous pollutants (NO2 and SO2), and diabetes was positively correlated with NO2 (in terms of the mortality risk). The effects of air pollutants were more pronounced in the cool season than in the warm season. The elderly (>65 years) and females were more vulnerable to air pollution. Studying effect estimates and their modifications by using YLL to detect premature death should support implementing health risk assessments, identifying susceptible groups and guiding policy-making and resource allocation according to specific local conditions.

Concentrations of the pesticide DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (dichlorodiphenyldichloroethylene), in the blood of Mexican Americans, were evaluated to determine their relationships with diabetes and diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 (unweighted N = 1,411, population estimate = 13,760,609). The sample included teens, 12–19 years old, which accounted for 19.8% of the data. The time of the study overlapped the banning of DDT in Mexico in the year 2000, and those participants born in Mexico were exposed to DDT before they immigrated to the US. We sought to better understand the relationship of DDT with diabetes in a race/ethnicity group prone to develop diabetes and exposed to DDT. In this study, nephropathy was defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria, and total diabetes was defined as diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥ 6.5%). The proportion with the isomer p,p′-DDT >0.086 ng/g (above the maximum limit of detection) was 13.3% for Mexican Americans born in the US, and 36.9% for those born in Mexico. Levels of p,p′-DDT >0.086 ng/g were associated with total diabetes with nephropathy (odds ratio = 4.42, 95% CI 2.23–8.76), and with total diabetes without nephropathy (odds ratio = 2.02, 95% CI 1.19–3.44). The third quartile of p,p′-DDE (2.99–7.67 ng/g) and the fourth quartile of p,p′-DDE (≥7.68 ng/g) were associated with diabetic nephropathy and had odds ratios of 5.32 (95% CI 1.05–26.87) and 14.95 (95% CI 2.96–75.48) compared to less than the median, respectively, whereas p,p′-DDE was not associated with total diabetes without nephropathy. The findings of this study differ from those of a prior investigation of the general adult US population in that there were more associations found with the Mexican Americans sample.

The incidence of diabetes is increasing rapidly in Chinese population, and it has been postulated that environmental factors may play a role in the etiology of diabetes. Therefore, we aimed to investigate the association between PAHs exposure and risk of diabetes in a community-based population of 2824 participants with completed questionnaires, measurements of biochemical indices, and urinary PAHs metabolites. We found that elevated urinary PAHs metabolites were associated, in a dose-dependent manner, with increased risk of diabetes. Particularly, these associations were more evident in subjects who were female, less than 55 years old, nonsmokers, and normal weight. In addition, there was a modest improvement in diabetes discrimination of prediction models when incorporating certain PAHs metabolites into conventional risk factors (CRF). Overall, our data suggested that there may be a dose-dependent relationship between PAHs metabolites and risk of diabetes among general Chinese population.

Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.