Hormonal Injustice: Environmental Toxicants as Drivers of Endocrine Health Disparities.

The toll of multiple endocrine disorders has increased substantially in recent decades, and marginalized populations bear a disproportionate burden of disease. Because of the significant individual and societal impact of these conditions, it is essential to identify and address all modifiable risk factors contributing to these disparities. Abundant evidence now links endocrine dysfunction with exposure to endocrine-disrupting chemicals (EDCs), with greater exposures to multiple EDCs occurring among vulnerable groups, such as racial/ethnic minorities, those with low incomes, and others with high endocrine disease burdens. Identifying and eliminating EDC exposures is an essential step in achieving endocrine health equity.

Arsenic metabolism, diabetes prevalence, and insulin resistance among Mexican Americans: A mendelian randomization approach.

Background: Differences in arsenic metabolism capacity may influence risk for type 2 diabetes, but the mechanistic drivers are unclear. We evaluated the associations between arsenic metabolism with overall diabetes prevalence and with static and dynamic measures of insulin resistance among Mexican Americans living in Starr County, Texas. Methods: We utilized data from cross-sectional studies conducted in Starr County, Texas, from 2010-2014. A Mendelian randomization approach was utilized to evaluate the associations between arsenic metabolism and type 2 diabetes prevalence using the intronic variant in the arsenic methylating gene, rs9527, as the instrumental variable for arsenic metabolism. To further assess mechanisms for diabetes pathogenesis, proportions of the urinary arsenic metabolites were employed to assess the association between arsenic metabolism and insulin resistance among participants without diabetes. Urinary biomarkers of arsenic metabolites were modeled as individual proportions of the total. Arsenic metabolism was evaluated both with a static outcome of insulin resistance, homeostatic measure of assessment (HOMA-IR), and a dynamic measure of insulin sensitivity, Matsuda Index. Results: Among 475 Mexican American participants from Starr County, higher metabolism capacity for arsenic is associated with higher diabetes prevalence driven by worse insulin resistance. Presence of the minor T allele of rs9527 is independently associated with an increase in the proportion of monomethylated arsenic (MMA%) and is associated with an odds ratio of 0.50 (95% CI: 0.24, 0.90) for type 2 diabetes. This association was conserved after potential covariate adjustment. Furthermore, among participants without type 2 diabetes, the highest quartile of MMA% was associated with 22% (95% CI: -33.5%, -9.07%) lower HOMA-IR and 56% (95% CI: 28.3%, 91.3%) higher Matsuda Index for insulin sensitivity. Conclusions: Arsenic metabolism capacity, indicated by a lower proportion of monomethylated arsenic, is associated with increased diabetes prevalence driven by an insulin resistant phenotype among Mexican Americans living in Starr County, Texas.

Transportation-related Environmental Mixtures and Diabetes Prevalence and Control in Urban/Metropolitan Counties in the United States.

Diabetes rates in the United States are staggering and climbing. Importantly, traditional risk factors fail to completely account for the magnitude of the diabetes epidemic. Environmental exposures, including urban and metropolitan transportation quality, are implicated as contributors to disease. Using data from the county-level Environmental Quality Index (EQI) developed for the United States, we analyzed associations between transportation and air quality environmental metrics with overall diabetes prevalence and control within urban/metropolitan counties in the United States from 2006 to 2012. Additionally, we examined effect modification by race/ethnicity through stratification based on the county-level proportion of minority residents. Last, we applied mixture methods to evaluate the effect of simultaneous poor transportation factors and worse air quality on the same outcomes. We found that increased county-level particulate matter air pollution and nitrogen dioxide along with reduced public transportation usage and lower walkability were all associated with increased diabetes prevalence. The minority proportion of the population influences some of these relationships as some of the effects of air pollution and the transportation-related environment are worse among counties with more minority residents. Furthermore, the transportation and air quality mixtures were found to be associated with increased diabetes prevalence and reduced diabetes control. These data further support the burgeoning evidence that poor environments amplify diabetes risk. Future cohort studies should explore the utility of environmental policies and urban planning as tools for improving metabolic health.

Metalloproteinase-9 in the ocular surface of patients with implanted Boston type 1 keratoprosthesis.

PURPOSE: To characterize the presence of ocular surface inflammation, using matrix metalloproteinase 9 (MMP-9) as a marker, in the ocular surface of eyes with implanted Boston Keratoprosthesis type 1 (KPro). METHODS: Patients with implanted KPro at a single tertiary center were recruited to assess ocular inflammation. MMP-9 was measured using InflammaDry® test in both eyes of each patient. The non-KPro eye served as control. Rate of positivity of MMP-9 was compared between groups. Possible associations between ocular surface inflammation and the development of postoperative complications were evaluated using univariate statistical analysis. RESULTS: Fifty eyes from 25 patients were included. The mean age was 50 years old. Non-inflammatory indications for KPro were predominant among patients. Eighty eight percent of KPro eyes had a positive test for MMP-9 while only 25% of control eyes were positive (p<001). The most common complications were retroprosthetic membrane, epithelial defects, and sterile corneal melt. The presence of a strong positive result was associated to a higher frequency of complications (80% of eyes) compared to a faint positive test (54%) and a negative test (33%). CONCLUSION: The KPro device appears to increase MMP-9 levels in the ocular surface. High MMP-9 levels may be associated with higher risk of complications. MMP-9 testing can be useful to assess subclinical ocular surface inflammation with a potential role in the postoperative care of KPro patients.

Relationships Between Urinary Metals and Diabetes Traits Among Mexican Americans in Starr County, Texas, USA.

Hispanics/Latinos have higher rates of type 2 diabetes (T2D), and the origins of these disparities are poorly understood. Environmental endocrine-disrupting chemicals (EDCs), including some metals and metalloids, are implicated as diabetes risk factors. Data indicate that Hispanics/Latinos may be disproportionately exposed to EDCs, yet they remain understudied with respect to environmental exposures and diabetes. The objective of this study is to determine how metal exposures contribute to T2D progression by evaluating the associations between 8 urinary metals and measures of glycemic status in 414 normoglycemic or prediabetic adults living in Starr County, Texas, a Hispanic/Latino community with high rates of diabetes and diabetes-associated mortality. We used multivariable linear regression to quantify the differences in homeostatic model assessments for pancreatic ß-cell function, insulin resistance, and insulin sensitivity (HOMA-ß, HOMA-IR, HOMA-S, respectively), plasma insulin, plasma glucose, and hemoglobin A1c (HbA1c) associated with increasing urinary metal concentrations. Quantile-based g-computation was utilized to assess mixture effects. After multivariable adjustment, urinary arsenic and molybdenum were associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels and higher HOMA-S. Additionally, higher urinary copper levels were associated with a reduced HOMA-ß. Lastly, a higher concentration of the 8 metal mixtures was associated with lower HOMA-ß, HOMA-IR, and plasma insulin levels as well as higher HOMA-S. Our data indicate that arsenic, molybdenum, copper, and this metal mixture are associated with alterations in measures of glucose homeostasis among non-diabetics in Starr County. This study is one of the first to comprehensively evaluate associations of urinary metals with glycemic measures in a high-risk Mexican American population.