Associations between metals and metabolomic profiles related to diabetes among adults in a rural region.

INTRODUCTION: Exposure to metals is associated with increased risk of type 2 diabetes (T2D). Potential mechanisms for metals-T2D associations involve biological processes including oxidative stress and disruption of insulin-regulated glucose uptake. In this study, we assessed whether associations between metal exposure and metabolite profiles relate to biological pathways linked to T2D. MATERIALS AND METHODS: We used data from 29 adults rural Colorado residents enrolled in the San Luis Valley Diabetes Study. Urinary concentrations of arsenic, cadmium, cobalt, lead, manganese, and tungsten were measured. Metabolic effects were evaluated using untargeted metabolic profiling, which included 61,851 metabolite signals detected in serum. We evaluated cross-sectional associations between metals and metabolites present in at least 50% of samples. Primary analyses adjusted urinary heavy metal concentrations for creatinine. Metabolite outcomes associated with each metal exposure were evaluated using pathway enrichment to investigate potential mechanisms underlying the relationship between metals and T2D. RESULTS: Participants had a mean age of 58.5 years (standard deviation = 9.2), 48.3% were female, 48.3% identified as Hispanic/Latino, 13.8% were current smokers, and 65.5% had T2D. Of the detected metabolites, 455 were associated with at least one metal, including 42 associated with arsenic, 22 with cadmium, 10 with cobalt, 313 with lead, 66 with manganese, and two with tungsten. The metabolic features were linked to 24 pathways including linoleate metabolism, butanoate metabolism, and arginine and proline metabolism. Several of these pathways have been previously associated with T2D, and our results were similar when including only participants with T2D. CONCLUSIONS: Our results support the hypothesis that metals exposure may be associated with biological processes related to T2D, including amino acid, co-enzyme, and sugar and fatty acid metabolism. Insight into biological pathways could influence interventions to prevent adverse health outcomes due to metal exposure.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Exacerbation of Renal, Cardiovascular, and Respiratory Outcomes Associated with Changes in Climate.

Exposure to environmental variables including declining air quality and increasing temperatures can exert detrimental effects on human health including acute exacerbations of chronic diseases. We aim to investigate the association between these exposures and acute health outcomes in a rural community in Colorado. Meteorological and adult emergency department visit data were retrospectively collected (2013-2017); for asthma outcomes, additional data were available (2003-2017). Daily environmental exposure data included PM10, maximum daily temperature (MDT), and mean humidity and precipitation. Total daily counts of emergency department (ED) diagnoses for myocardial infarction, congestive heart failure, urolithiasis, and exacerbation of chronic obstructive pulmonary disease (COPD) and asthma, were calculated during the study period. Time series models using generalized estimating equations were fit for each disease and included all four environmental factors. Between 2013 and 2017, asthma and COPD exacerbation accounted for 30.8% and 25.4% of all ED visits (n=5,113), respectively. We found that for every 5˚C increase in MDT, the rate of urolithiasis visits increased by 13% (95% CI: 2%, 26%) and for every 10µg/m3 increase in 3-day moving average PM10, the rate of urolithiasis visits increased by 7% (95% CI: 1%, 13%). The magnitude of association between 3-day moving average PM10 and rate of urolithiasis visits increased with increasing MDT. The rate of asthma exacerbation significantly increased as 3-day, 7-day, and 21-day moving average PM10 increased. This retrospective study on ED visits is one of the first to investigate the impact of several environmental exposures on adverse health outcomes in a rural community. Research into mitigating the negative impacts of these environmental exposures on health outcomes is needed.

Open-source environmental data as an alternative to snail surveys to assess schistosomiasis risk in areas approaching elimination.

BACKGROUND: Although the presence of intermediate snails is a necessary condition for local schistosomiasis transmission to occur, using them as surveillance targets in areas approaching elimination is challenging because the patchy and dynamic quality of snail host habitats makes collecting and testing snails labor-intensive. Meanwhile, geospatial analyses that rely on remotely sensed data are becoming popular tools for identifying environmental conditions that contribute to pathogen emergence and persistence. METHODS: In this study, we assessed whether open-source environmental data can be used to predict the presence of human Schistosoma japonicum infections among households with a similar or improved degree of accuracy compared to prediction models developed using data from comprehensive snail surveys. To do this, we used infection data collected from rural communities in Southwestern China in 2016 to develop and compare the predictive performance of two Random Forest machine learning models: one built using snail survey data, and one using open-source environmental data. RESULTS: The environmental data models outperformed the snail data models in predicting household S. japonicum infection with an estimated accuracy and Cohen's kappa value of 0.89 and 0.49, respectively, in the environmental model, compared to an accuracy and kappa of 0.86 and 0.37 for the snail model. The Normalized Difference in Water Index (an indicator of surface water presence) within half to one kilometer of the home and the distance from the home to the nearest road were among the top performing predictors in our final model. Homes were more likely to have infected residents if they were further from roads, or nearer to waterways. CONCLUSION: Our results suggest that in low-transmission environments, leveraging open-source environmental data can yield more accurate identification of pockets of human infection than using snail surveys. Furthermore, the variable importance measures from our models point to aspects of the local environment that may indicate increased risk of schistosomiasis. For example, households were more likely to have infected residents if they were further from roads or were surrounded by more surface water, highlighting areas to target in future surveillance and control efforts.

Development and application of an evidence-based directed acyclic graph to evaluate the associations between metal mixtures and cardiometabolic outcomes.

Objectives: Specifying causal models to assess relationships among metal mixtures and cardiometabolic outcomes requires evidence-based models of the causal structures; however, such models have not been previously published. The objective of this study was to develop and evaluate a directed acyclic graph (DAG) diagraming metal mixture exposure and cardiometabolic outcomes. Methods: We conducted a literature search to develop the DAG of metal mixtures and cardiometabolic outcomes. To evaluate consistency of the DAG, we tested the suggested conditional independence statements using linear and logistic regression analyses with data from the San Luis Valley Diabetes Study (SLVDS; n=1795). We calculated the proportion of statements supported by the data and compared this to the proportion of conditional independence statements supported by 1,000 DAGs with the same structure but randomly permuted nodes. Next, we used our DAG to identify minimally sufficient adjustment sets needed to estimate the association between metal mixtures and cardiometabolic outcomes (i.e., cardiovascular disease, fasting glucose, and systolic blood pressure). We applied them to the SLVDS using Bayesian kernel machine regression, linear mixed effects, and Cox proportional hazards models. Results: From the 42 articles included in the review, we developed an evidence-based DAG with 74 testable conditional independence statements (43 % supported by SLVDS data). We observed evidence for an association between As and Mn and fasting glucose. Conclusions: We developed, tested, and applied an evidence-based approach to analyze associations between metal mixtures and cardiometabolic health.

Occurrence of Occupational Injuries and Within Day Changes in Wet Bulb Temperature Among Sugarcane Harvesters.

OBJECTIVE: Climate change has implications for human health worldwide, with workers in outdoor occupations in low- to middle-income countries shouldering the burden of increasing average temperatures and more frequent extreme heat days. An overlooked aspect of the human health impact is the relationship between heat exposure and increased risk of occupational injury. In this study, we examined the association between occupational injury occurrence and changes in outdoor temperatures through the workday among a cohort of Guatemalan sugarcane harvesters. METHODS: Occupational injuries recorded for the 2014/2015 to 2017/2018 harvest seasons were collected from a large agribusiness employing male sugarcane harvesters in Southwest Guatemala. Wet Bulb Globe Temperature (WBGT) for the same period was collected from the El Balsamo weather station. We used a logistic mixed effects model to examine the association between injury occurrence and (1) the average WBGT during the hour injury was recorded, (2) the average WBGT during the hour prior to the injury being recorded, and (3) the change in the hourly average WBGT prior to the injury being recorded. RESULTS: There were 155 injuries recorded during the study period. Injuries were recorded most often between 14:00 and 16:00 (n = 62, 40%) followed by 8:00 and 10:00 (n = 56, 36%). There were significant differences in the average hourly WBGT and the hour in which injuries were recorded (p-value <.001). There were no observable associations between average hourly WBGT (OR: 1.00, 95%CI: 0.94, 1.05; p-value: 0.87), lagged average hourly WBGT (OR: 1.01, 95%CI: 0.97, 1.05; p-value: 0.71), or change in average hourly WBGT (OR: 0.96, 95%CI: 0.89, 1.04; p-value: 0.35) and recorded occupational injury. CONCLUSIONS: This is the first study that has examined how changes in WBGT throughout the day are related to occupational injury among agricultural workers. Although this study did not demonstrate an association, there is a need for future research to examine how various measurements of WBGT exposure are related to occupational injury in agricultural worker populations.

Urinary concentrations of metals before and after volcanic eruption: a natural experiment surrounding the eruption of Volcán de Fuego, 2018.

Volcanic eruptions increase environmental heavy metal concentrations, yet little research has been performed on their extrapulmonary human health effects. We fortuitously collected biological samples in a cohort of Guatemalan sugarcane cutters in the area surrounding Volcán de Fuego before and after the June 2018 eruption. We sought to determine whether stratovolcanic activity was associated with changes in urinary concentrations of heavy metals in a cohort of sugarcane workers. In this exploratory analysis, we found significant increases in urinary arsenic, (ß = 1.46, P < 0.0001), cadmium (ß = 1.03, P < 0.0001), and lead (ß = 0.87, P = 0.003) in participants with residential proximity to Volcán de Fuego as compared to participants farther away, suggesting that volcanic activity could be associated with acute heavy metal exposures. This natural experiment is, to our knowledge, the first of its kind and suggests a need for more research into heavy metal exposure-related health impacts of volcanic eruptions.

The S.I.T.E. Framework: A Novel Approach for Sustainably Integrating Trauma-Informed Approaches in Schools.

Students who present as dysregulated due to the impacts of trauma and toxic stress can challenge educators and find themselves improperly or insufficiently supported, punitively consequenced and unable to equitably access education. Trauma-informed approaches based on an understanding of brain development and function have been put forth as best practice for supporting students with trauma histories. The novel Sustainably Integrated Trauma-Informed Education Framework (S.I.T.E. Framework) facilitates systemic integration of trauma-informed approaches across a school and was developed through a community-informed process to address implementation challenges traditionally linked to trauma-informed initiatives. The S.I.T.E Framework promotes the science-based content of the Neurosequential Model in Education (NME) and was piloted during the 2017-18 school year at a metropolitan elementary school in Colorado. Mixed analytic methods identified four components, 1) establish and facilitate school-based Core Team, 2) deliver school-wide professional development training, 3) provide on-site staff support and consultation and 4) conduct a comprehensive evaluation as critical to the successful implementation of the framework. Pilot testing of the S.I.T.E. Framework's innovative, multicomponent structure illustrates the potential for sustainable, whole-school integration of brain-based, trauma-informed approaches that are supportive of both educators and students regardless of their trauma history.

A Longitudinal Study of Exposure to Manganese and Incidence of Metabolic Syndrome.

The association between manganese (Mn) and metabolic syndrome (MetS) is unclear, and no prior study has studied this association longitudinally. The aim of this study was to assess longitudinal associations of Mn exposure with MetS and metabolic outcomes. We used data from the San Luis Valley Diabetes Study (SLVDS), a prospective cohort from rural Colorado with data collected from 1984−1998 (n = 1478). Urinary Mn was measured at baseline (range = 0.20−42.5 µg/L). We assessed the shape of the cross-sectional association between Mn and MetS accounting for effect modification by other metals at baseline using Bayesian kernel machine regression. We assessed longitudinal associations between baseline quartiles of Mn and incident MetS using Fine and Gray competing risks regression models (competing risk = mortality) and between quartiles of Mn and metabolic outcomes using linear mixed effects models. We did not observe evidence that quartiles of Mn were associated with incident MetS (p-value for trend = 0.52). Quartiles of Mn were significantly associated with lower fasting glucose (p-value for trend < 0.01). Lead was found to be a possible effect modifier of the association between Mn and incident MetS. Mn was associated with lower fasting glucose in this rural population. Our results support a possible beneficial effect of Mn on diabetic markers.

Overview of the cardiovascular effects of environmental metals: New preclinical and clinical insights.

Environmental causes of cardiovascular diseases (CVDs) are global health issues. In particular, an association between metal exposure and CVDs has become evident but causal evidence still lacks. Therefore, this symposium at the Society of Toxicology 2022 annual meeting addressed epidemiological, clinical, pre-clinical animal model-derived and mechanism-based evidence by five presentations: 1) An epidemiologic study on potential CVD risks of individuals exposed occupationally and environmentally to heavy metals; 2) Both presentations of the second and third were clinical studies focusing on the potential link between heavy metals and pulmonary arterial hypertension (PAH), by presenting altered blood metal concentrations of both non-essential and essential metals in the patients with PAH and potential therapeutic approaches; 3) Arsenic-induced atherosclerosis via inflammatory cells in mouse model; 4) Pathogenic effects on the heart by adult chronic exposure to very low-dose cadmium via epigenetic mechanisms and whole life exposure to low dose cadmium via exacerbating high-fat-diet-lipotoxicity. This symposium has brought epidemiologists, therapeutic industry, physicians, and translational scientists together to discuss the health risks of occupational and environmental exposure to heavy metals through direct cardiotoxicity and indirect disruption of homeostatic mechanisms regulating essential metals, as well as lipid levels. The data summarized by the presenters infers a potential causal link between multiple metals and CVDs and defines differences and commonalities. Therefore, summary of these presentations may accelerate the development of efficient preventive and therapeutic strategies by facilitating collaborations among multidisciplinary investigators.

Characterization of Colorado residents and radon reduction behaviors through latent class analysis and path models.

Radon is a naturally occurring radioactive gas that enters homes through cracks in the foundation where accumulated levels can cause lung cancer. Within the United States (U.S.), state level radon reduction strategies rely on education and outreach to motivate people to test and mitigate their home. Only about 5% of the housing units in Colorado, U.S. have been tested for radon. This study looks at the 2012 Behavioral Risk Factors Surveillance System (BRFSS) in Colorado to identify distinct groups of people using Latent Class Analysis, and compares radon awareness, testing, and mitigation to understand underlying differences of radon reduction behaviors using path models. Five classes were identified: 1) Wealthy Young Families, 2) Older Singles, 3) Empty Nesters, 4) Smokers, and 5) Struggling Young Families. Significant differences in responses to radon survey questions existed across groups in which Struggling Young Families were the least likely to be aware of radon, have tested their home for radon, and have their home mitigated. Average radon awareness, testing, and mitigation appeared to be influenced by financial stress. Results from this study can be used to tailor future radon interventions and policy initiatives to enhance equity of radon reduction behaviors including legal framework to ensure radon mitigation takes place in rental properties.

Integrating Environment and Aging Research: Opportunities for Synergy and Acceleration.

Despite significant overlaps in mission, the fields of environmental health sciences and aging biology are just beginning to intersect. It is increasingly clear that genetics alone does not predict an individual's neurological aging and sensitivity to disease. Accordingly, aging neuroscience is a growing area of mutual interest within environmental health sciences. The impetus for this review came from a workshop hosted by the National Academies of Sciences, Engineering, and Medicine in June of 2020, which focused on integrating the science of aging and environmental health research. It is critical to bridge disciplines with multidisciplinary collaborations across toxicology, comparative biology, epidemiology to understand the impacts of environmental toxicant exposures and age-related outcomes. This scoping review aims to highlight overlaps and gaps in existing knowledge and identify essential research initiatives. It begins with an overview of aging biology and biomarkers, followed by examples of synergy with environmental health sciences. New areas for synergistic research and policy development are also discussed. Technological advances including next-generation sequencing and other-omics tools now offer new opportunities, including exposomic research, to integrate aging biomarkers into environmental health assessments and bridge disciplinary gaps. This is necessary to advance a more complete mechanistic understanding of how life-time exposures to toxicants and other physical and social stressors alter biological aging. New cumulative risk frameworks in environmental health sciences acknowledge that exposures and other external stressors can accumulate across the life course and the advancement of new biomarkers of exposure and response grounded in aging biology can support increased understanding of population vulnerability. Identifying the role of environmental stressors, broadly defined, on aging biology and neuroscience can similarly advance opportunities for intervention and translational research. Several areas of growing research interest include expanding exposomics and use of multi-omics, the microbiome as a mediator of environmental stressors, toxicant mixtures and neurobiology, and the role of structural and historical marginalization and racism in shaping persistent disparities in population aging and outcomes. Integrated foundational and translational aging biology research in environmental health sciences is needed to improve policy, reduce disparities, and enhance the quality of life for older individuals.

County-Level Social Vulnerability Is Positively Associated with Cardiometabolic Disease in Colorado.

Cardiometabolic diseases are a group of interrelated diseases that pose greater burden among socially vulnerable communities. The social vulnerability index (SVI) identifies communities vulnerable to emergencies and may also help determine communities at risk of adverse chronic health outcomes. However, no studies have examined the relationship between the SVI and cardiometabolic health outcomes in Colorado or focused on rural settings. The aim of this ecological study was to determine whether the county-level SVI is associated with county-level cardiometabolic health indicators with a particular focus on rurality and racial/ethnic diversity. We obtained 2014 SVI scores from the Centers for Disease Control and Prevention (scored 0-1; higher = more vulnerable) and 2013-2015 cardiometabolic health estimates from the Colorado Department of Public Health and Environment. The distribution of social determinants of health was spatially evaluated. Bivariate relationships between the SVI and cardiometabolic indicators were estimated using simple linear regression models. The highest SVI scores were observed in rural areas, including the San Luis Valley (mean: 0.78, median: 0.91), Southeast (mean: 0.72, median: 0.73), and Northeast (mean: 0.66, median: 0.76) regions. Across Colorado, the SVI accounted for 41% of the variability in overweight and obesity prevalence (p < 0.001), 17% of the variability in diabetes prevalence (p = 0.001), and 58% of the age-adjusted myocardial infarction hospitalization rate (p < 0.001). SVI values may be useful in determining a community's burden of cardiometabolic diseases.

The impact of family physicians in rural maternity care.

BACKGROUND: Reduced access to maternity care in rural areas of the United States presents a significant burden to pregnant persons and infants. The objective of this study was to estimate the impact of family physicians (FPs) on access to maternity care in rural United States hospitals, especially where other providers may not be available. METHODS: We administered a survey to 216 rural hospitals in 10 US states inquiring about the number of babies delivered from 2013 to 2017, the types of delivering physicians, and the maternity services offered. We calculated the percentage of rural hospitals in our sample where FPs performed vaginal deliveries, cesareans, and vaginal births after cesarean (VBACs), and the percentage of all babies delivered by FPs. We estimated the distance patients would have to travel for care if FPs were not providing care locally. RESULTS: The final study population consisted of 185 rural hospitals. FPs delivered babies in 67% of these hospitals and were the only physicians who delivered babies in 27% of these hospitals. FPs provided VBAC at 18% and cesarean birth services at 46% of the rural hospitals, but with wide geographic differences. Many patients would have to drive an average of 86 miles round-trip to access care if those FPs were to stop delivering. CONCLUSIONS: Family physicians are essential providers of maternity care in the rural United States. Family Medicine residency programs should ensure that trainees who intend to practice in rural locations have adequate maternity care training to maintain and expand access to maternity care for rural patients and their families.

Environmental metal exposures and kidney function of Guatemalan sugarcane workers.

BACKGROUND: Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu). Whether metal exposures contribute to kidney dysfunction in populations at risk for CKDu remains unresolved. OBJECTIVE: Urinary metals (arsenic, cadmium, nickel, and uranium) were examined in 222 sugarcane cutters in Guatemala at three time points over 1 year. METHODS: We explored the relationships between metal concentrations and markers of kidney function using multivariable linear mixed-effect models. RESULTS: Arsenic, cadmium, and nickel were detected in the majority of the 340 urine samples and were generally within limits previously considered to be nonnephrotoxic. Nevertheless, higher urine cadmium was inversely associated with estimated glomerular filtration rate (eGFR) (ß: -4.23, 95% confidence interval [CI]: -6.92, -1.54) and positively associated with neutrophil gelatinase-associated lipocalin (NGAL) (ß: 2.92, 95% CI: 1.20, 4.64). Higher urine arsenic was also inversely associated with eGFR (ß: -4.36, 95% CI: -7.07, -1.64). SIGNIFICANCE: Our findings suggest that exposures to metals, including cadmium and arsenic, might contribute to kidney toxicity seen in workers at risk for CKDu. These findings are consistent with the potential for metal nephrotoxicity at lower than expected levels in the setting of manual work in a very hot environment.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). CONCLUSIONS: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Multipollutant, longitudinal analysis of the association between urinary tungsten and incident diabetes in a rural population.

BACKGROUND: Cross-sectional studies suggest tungsten (W) exposure may be associated with diabetes. We assessed longitudinal associations between urinary W and fasting glucose, 2-hour glucose, insulin resistance (HOMA-IR), ß-cell function (HOMA-ß), and incident type 2 diabetes. METHODS: We used data from 1,609 Hispanic and non-Hispanic White adults with 20 to 74 years of age residing in rural Colorado and participating in the San Luis Valley Diabetes Study. Urinary metal exposure values were measured at baseline and natural log-transformed. We assessed longitudinal associations between urinary W and continuous outcome measures using linear-mixed effect models and associations with incident diabetes using Fine and Gray competing risks regression models (competing event = all-cause mortality). The main adjustment set of covariates included: age, sex, ethnicity, education, smoking status, hypertension, body mass index, caloric intake, alcohol intake, and urinary creatinine levels. Secondary models were further adjusted for arsenic, cadmium, and lead exposures. We assessed whether sex or ethnicity were effect modifiers. RESULTS: At baseline, the median W concentration was 0.22 µg/L (interquartile range = 0.20, 0.59). In the main cross-sectional analyses, lnW levels were significantly associated with 3% higher lnHOMA-IR (95% CI = 1 to 5). In the main longitudinal models, lnW was significantly associated with 1% higher natural log-transformed fasting glucose (95% CI = <1 to 1), 3% higher natural log-transformed HOMA-IR (95% CI = 2 to 5), and 28% higher incident diabetes (subdistribution hazard ratio=1.28, 95% CI = 1.09 to 1.50). Results remained significant when further adjusting for other metals. We observed evidence for effect modification by sex and ethnicity. CONCLUSION: Urinary W was longitudinally associated with adverse metabolic health indicators.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality-a measure of dissolved particles including ions, glucose, and urea-is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89-0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

Assessment of Rural-Urban and Geospatial Differences in Perceived Handgun Access and Reported Suicidality Among Youth in Colorado.

Importance: Suicide is the second leading cause of death in adolescents, with firearms the most common method, especially in rural communities. Identifying where to target lethal means safety interventions could better leverage limited resources. Objectives: To understand the associations of rurality, school-level prevalence of easy handgun access, and suicidality measures in Colorado youth, to explore spatial distribution of school-level measures, and to identify communities with high prevalence of both easy handgun access and suicidality. Design, Setting, and Participants: This cross-sectional study used data from the 2019 Healthy Kids Colorado Survey, an anonymous cross-sectional school-based survey conducted at 256 participating Colorado high schools. Participants included students from schools recruited for statewide population-based estimates and additional schools opting in. Data were analyzed from November 9, 2020, to March 13, 2021. Exposures: Urban-centric locale according to a 7-level continuum. Geocoded location of schools was used for spatial analysis. Main Outcomes and Measures: The main outcomes were weighted prevalence for easy handgun access and 4 measures of mental health and suicidality in the previous year (ie, feeling sad for 2 weeks and considering suicide, planning suicide attempt, or attempting suicide in the past year). Results: A total of 59 556 students (49.7% [95% CI, 49.3%-50.1%] male and 50.3% [95% CI, 49.9%-50.7%] female; 53.9% [95% CI, 53.5%-54.3%] in 9th and 10th grade; 36.4% [95% CI, 36.0%-36.8%] Hispanic and 50.8% [95% CI, 50.4%-51.2%] non-Hispanic White) from 256 schools participated. Most schools were rural or in small towns (56.8% [95% CI, 50.7%-62.9%]), while more students participated from urban and suburban schools (57.8% [95% CI, 57.6%-58.0%]). Prevalence of perceived easy access to handguns increased with increasing rurality, with 36.2% (95% CI, 35.2%-37.1%) of students in rural (remote) schools reporting easy access, compared with 18.2% (95% CI, 17.3%-19.1%) for city (large) schools. The spatial distribution of easy handgun access and suicidality measures had minimal overlap, but there was correlation at school-level between easy handgun access and considering suicide (ρ = 0.203 [95% CI, 0.0748-0.331]), planning suicide (ρ = 0.300 [95% CI, 0.173-0.427]), and attempting suicide (ρ = 0.218 [95% CI, 0.0869-0.350) in the previous year. The highest quartile for prevalence of both perceived easy access to handguns and planning suicide in the previous year included 21 schools (81.0% [95% CI, 64.0%-97.9%] rural [remote] or rural [distant]). Conclusions and Relevance: These findings suggest that rural-remote communities in Colorado may benefit most from interventions focused on limiting youth access to handguns when youth are in crisis, with some communities at especially high risk. Spatially referenced data may improve targeting interventions to where they are needed most.