Hysterectomy, oophorectomy and risk of non-Hodgkin's lymphoma.

Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.

A Longitudinal Study of Sleep Habits and Leukemia Incidence Among Postmenopausal Women.

We sought to assess the relationship between sleep duration, sleep disturbance, and leukemia incidence among postmenopausal women. This study included 130,343 postmenopausal women aged 50-79 years who were enrolled in the Women's Health Initiative (WHI) during 1993-1998. Information on self-reported typical sleep duration and sleep disturbance was obtained by questionnaire at baseline, and sleep disturbance level was defined according to the Women's Health Initiative Insomnia Rating Scale (WHIIRS). WHIIRS scores of 0-4, 5-8, and 9-20 comprised 37.0%, 32.6%, and 30.4% of all women, respectively. After an average of 16.4 years (2,135,109 cumulative person-years) of follow-up, 930 of the participants were identified as having incident leukemia. Compared with women with the lowest level of sleep disturbance (WHIIRS score 0-4), women with higher sleep disturbance levels (WHIIRS scores of 5-8 and 9-20) had 22% (95% confidence interval (CI): 1.04, 1.43) and 18% (95% CI: 1.00, 1.40) excess risks of leukemia, respectively, after multivariable adjustment. A significant dose-response trend was found for the association between sleep disturbance and leukemia risk (P for trend = 0.048). In addition, women with the highest level of sleep disturbance had a higher risk of myeloid leukemia (for WHIIRS score 9-20 vs. WHIIRS score 0-4, hazard ratio = 1.39, CI: 1.05, 1.83). Higher sleep disturbance level was associated with increased risk of leukemia, especially for myeloid leukemia among postmenopausal women.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with demonstrated renal and cardiovascular disease benefit. This study evaluates the role of SGLT2 inhibitors on the survival of non-small cell lung cancer (NSCLC) patients. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Twenty four thousand nine hundred fifteen NSCLC patients newly diagnosed between 2014 and 2017 with pre-exiting diabetes and aged 66 years or older were included and followed to the end of 2019. Information on SGLT2 inhibitors use was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor use was associated with significantly reduced mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.60-0.77) with stronger association for longer duration of use (HR = 0.54, 85% CI = 0.44-0.68). Further, we found that SGLT2 inhibitor use was associated with a significant reduced risk of mortality regardless of patients' demographic, tumour characteristics and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitors use was associated with improved overall survival of NSCLC patients with pre-existing diabetes. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Body size over the adult life course and the risk of colorectal cancer among postmenopausal women.

OBJECTIVE: To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women. DESIGN: Prospective cohort study. SETTING: Forty clinical centres in the USA. PARTICIPANTS: Totally, 79 034 postmenopausal women in the Women's Health Initiative Observational Study. RESULTS: During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18-50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively. CONCLUSION: Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.

Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls.

PURPOSE: Aging associated with progressive declines in physical function is well-known; however, it is unclear how breast cancer diagnosis affects the trajectories of physical function over a long period of time. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. METHODS: 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. RESULTS: We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~ 7 pounds shortly after breast cancer diagnosis, and then improved over time. CONCLUSION: Our study revealed that older breast cancer survivors relative to older women without cancer had significantly worse declines in grip strength and gait speed. Breast cancer survivors also had a sharp, short-term drop followed by gradual improvement over time in quadriceps strength. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.

Mediation analysis of social isolation and mortality by health behaviors.

Social isolation associated with greater risk for mortality is well documented, however, it is unclear whether and the extent to which social isolation influences mortality through health behaviors. We therefore assessed the mediation between social isolation and mortality by health behaviors. 15,000 adults ages 18-89 years in the Third National Health and Nutrition Examination Survey in the US (NHANES III) (1988-1994) were followed through 2015. The outcomes of overall and cause-specific mortality were assessed by linking with the National Death Index. Social isolation was based on a modified Social Network Index. Mediation analyses were conducted under the counterfactual framework. Compared with participants who were not socially isolated, those who were isolated had significantly increased risk for overall mortality (HR = 1.33, 95% CI: 1.15-1.54), cardiovascular disease (CVD)-specific mortality (HR = 1.28, 95% CI: 1.01-1.62) and mortality from causes other than CVD or cancer (HR = 1.53, 95% CI: 1.22-1.90). Social isolation was not independently associated with risk for cancer-specific mortality. The association between social isolation and cancer-specific mortality was largely (74%) mediated by health behaviors, including smoking, physical activity and quality of diet. The associations between social isolation and CVD or other specific mortality were partly (about one-fifth) explained by unhealthy behaviors. In conclusion, the extent to which social isolation and mortality was mediated by healthy behaviors varies by causes of death. Given mounting evidence that social isolation is increasing in society, it is important to add social isolation to the list of public health concerns in addition to conventional risk factors.

Association between exposure to parabens and total mortality in US adults.

BACKGROUND: Parabens are a group of endocrine disruptors that have been associated with health effects such as hypertension, diabetes, oxidative stress and obesity, which are associated with increased mortality risk over time. Women are exposed to higher paraben levels than men through use of consumer products. The current prospective study examines paraben exposure in association with mortality risk for women and men. METHODS: We analyzed 2005-2008 National Health and Nutrition Examination Survey (NHANES) data on urinary paraben analyte concentrations and covariates in adults aged 20 years and over, prospectively linked to National Center for Health Statistics (NCHS) mortality through 2015 (N = 2939). Proportional hazard regression models examined mortality risk in association with exposures, controlling for covariates for women and men. Covariates included age, race/ethnicity, smoking, education, income, body mass index, physical activity, self-reported health status and baseline health conditions. RESULTS: Women were exposed to significantly higher concentrations of all studied parabens than men. Exposures were highest for methyl paraben. Women had significantly higher mortality risk in association with higher natural log exposure to ethyl (HR = 2.048, 95% CI 1.164-3.601), methyl (HR = 1.312, 95% CI 1.013-1.700), butyl (HR = 2.719, 95% CI 1.591-4.647) and total parabens (HR = 1.292, 95% CI 1.006-1.659). Exposure concentrations were associated with higher mortality risk for men only for ethyl paraben (HR = 2.532, 95% CI 1.217-5.268). DISCUSSION: Women were found to be at greater mortality risk in association with exposure to ethyl, methyl, butyl and total parabens. These findings require confirmatory research but add to the evidence base that exposure to parabens, probably through consumer products, may have adverse effects on human health, especially for women.

Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women.

BACKGROUND: Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. METHODS: A total of 128,623 Black and White women aged 50-79 years from the Women's Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. RESULTS: Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. CONCLUSION: Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.

BMI trajectory and subsequent risk of type 2 diabetes among middle-aged women.

BACKGROUND AND AIMS: Little is known about how weight trajectories among women during menopausal transition and beyond may be related to risk of type 2 diabetes mellitus (T2DM). The aim of this study was to examine associations between body mass index (BMI) trajectories over 20 years, age of obesity onset, cumulative obese-years and incidence of T2DM among middle-aged women. METHODS AND RESULTS: 12,302 women enrolled in the Australian Longitudinal Study on Women's Health (ALSWH) were surveyed in 1996 (Survey 1, age 45-50), 1998 and then every three years to 2016. Self-reported weight and height were collected for up to eight time points. Incident diabetes was assessed via validated self-report of physician-diagnosed diabetes. Growth mixture models were used to identify distinct BMI trajectories. A total of 1380 (11.2%) women newly developed T2DM over an average 16 years of follow-up. Seven distinct BMI trajectories were identified with differential risk of developing T2DM. Initial BMI was positively associated with T2DM risk. We also observed that risk of T2DM was positively associated with rapid weight increase, early age of obesity onset and greater obese-years. CONCLUSION: Slowing down weight increases, delaying the onset of obesity, or reducing cumulative exposure to obesity may substantially lower the risk of developing T2DM.

Exposure to heavy metals from point pollution sources and risk of incident type 2 diabetes among women: a prospective cohort analysis.

Heavy metal exposures may contribute to diabetes risk but prospective studies are uncommon. We analyzed the Australian Longitudinal Study on Women's Health (three cohorts aged 18-23, 45-50, or 70-75 at baseline in 1996, N = 34,191) merged with emissions data for 10 heavy metals (As, Be, Co, Cr, Cu, Hg, Mn, Ni, Pb, Zn) from the National Pollutant Inventory. Over 20-year follow-up, 2,584 women (7.6%) reported incident diabetes. Cox proportional hazards regression models showed that women aged 45-50 at baseline had higher diabetes risk in association with exposure to total air emissions, total water emissions, all individual metals air emissions, and six individual water emissions. After correction for false discovery rate, nine of 11 air emissions and five water emissions remained significant. Associations were not observed for land-based emissions, or for younger or older cohorts. Emissions were dominated by mining, electricity generation and other metals-related industrial processes.

Age of obesity onset, cumulative obesity exposure over early adulthood and risk of type 2 diabetes.

AIMS/HYPOTHESIS: Obesity is a risk factor for type 2 diabetes, yet little is known about how timing and cumulative exposure of obesity are related to disease risk. The aim of this study was to examine the associations between BMI trajectories, age of onset of obesity and obese-years (a product of degree and duration of obesity) over early adulthood and subsequent risk of type 2 diabetes. METHODS: Women aged 18-23 years at baseline (n = 11,192) enrolled in the Australian Longitudinal Study on Women's Health (ALSWH) in 1996 were followed up about every 3 years via surveys for up to 19 years. Self-reported weights were collected up to seven times. Incident type 2 diabetes was self-reported. A growth mixture model was used to identify distinct BMI trajectories over the early adult life course. Cox proportional hazards regression models were used to examine the associations between trajectories and risk of diabetes. RESULTS: One hundred and sixty-two (1.5%) women were newly diagnosed with type 2 diabetes during a mean of 16 years of follow-up. Six distinct BMI trajectories were identified, varying by different initial BMI and different slopes of increase. Initial BMI was positively associated with risk of diabetes. We also observed that age at onset of obesity was negatively associated with risk of diabetes (HR 0.87 [95% CI 0.79, 0.96] per 1 year increment), and number of obese-years was positively associated with diabetes (p for trend <0.0001). CONCLUSIONS/INTERPRETATION: Our data revealed the importance of timing of obesity, and cumulative exposure to obesity in the development of type 2 diabetes in young women, suggesting that preventing or delaying the onset of obesity and reducing cumulative exposure to obesity may substantially lower the risk of developing diabetes.

Physical activity and risk of bladder cancer among postmenopausal women.

Physical activity is associated with decreased risk for many cancers. Studies on the association between physical activity and risk of bladder cancer are limited, and findings are inconsistent. Postmenopausal women (mean age = 63.3) were recruited into the Women's Health Initiative from 1993 to 1998. Self-reported baseline information on physical activity and other covariates were available in 141 288 participants. Incident bladder cancer cases were collected through 2018 and centrally adjudicated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazard regression models. Effect modification due to smoking was assessed. During an average of 18.5 years of follow-up, 817 bladder cancer cases were identified. Compared to physically inactive women, those who engaged in ≥15 MET-hours/week of total physical activity, ≥8.75 MET-hours/week of walking or ≥11.25 MET-hours/week of moderate to vigorous physical activity had lower risk of bladder cancer (HR = 0.74, 95% CI: 0.59-0.94, P for linear trend = .02; HR = 0.79, 95% CI: 0.63-0.98, P for linear trend = .03; and HR = 0.76, 95% CI: 0.61-0.94, P for linear trend = .02, respectively). No effect modification was found by smoking status (P for interaction = .06, 0.91 and 0.27, respectively). We found that total physical activity, walking and moderate to vigorous physical activity were inversely associated with bladder cancer incidence among postmenopausal women in a dose-response manner. Physical activity may play a potential role in the primary prevention of bladder cancer. Further studies with objective measurements of physical activity are needed to confirm these findings.

Birth weight, weight over the adult life course and risk of breast cancer.

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50-79 years without breast cancer at enrollment (1993-1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6-8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79-0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.

Association between selenium intake and breast cancer risk: results from the Women's Health Initiative.

PURPOSE: It has been hypothesized that selenium (Se) can prevent cancer, and that Se deficiency may be associated with an increased risk of breast cancer. However, findings from epidemiological studies have been inconsistent. The objective of this study was to assess the association between Se intake and risk of breast cancer in the Women's Health Initiative (WHI). METHODS: This study included 145,033 postmenopausal women 50-79 years who completed baseline questionnaires between October 1993 and December 1998, which addressed dietary and supplemental Se intake and breast cancer risk factors. The association between baseline Se intake and incident breast cancer was examined in Cox proportional hazards analysis. RESULTS: During a mean follow-up of 15.5 years, 9487 cases of invasive breast cancer were identified. Total Se (highest versus lowest quartile: HR 1.00, 95% CI 0.92-1.09, Ptrend = 0.66), dietary Se (highest versus lowest quartile: HR 0.99, 95% CI 0.89-1.08, Ptrend = 0.61), and supplemental Se (yes versus no: HR 0.99, 95% CI 0.95-1.03) were not associated with breast cancer incidence. CONCLUSIONS: This study indicates that Se intake is not associated with incident breast cancer among postmenopausal women in the United States. Further studies are needed to confirm our findings by using biomarkers such as toenail Se to reduce the potential for misclassification of Se status.

Impacts of Coal Use on Health.

This article reviews evidence for the public health impacts of coal across the extraction, processing, use, and waste disposal continuum. Surface coal mining and processing impose public health risks on residential communities through air and water pollution. Burning coal in power plants emits more nitrogen oxides, sulfur dioxide, particulate matter, and heavy metals per unit of energy than any other fuel source and impairs global public health. Coal ash disposal exposes communities to heavy metals and particulate matter waste. Use of coal in domestic households causes public health harm concentrated in developing nations. Across the coal continuum, adverse impacts are disproportionately felt by persons of poor socioeconomic status, contributing to health inequities. Despite efforts to develop renewable energy sources, coal use has not declined on a global scale. Concentrated efforts to eliminate coal as an energy source are imperative to improve public health and avert serious climate change consequences.

The association between type 2 diabetes mellitus and bladder cancer risk among postmenopausal women.

INTRODUCTION: Evidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent. METHODS: A total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk. RESULTS: During a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes. CONCLUSION: Diabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

Latent Class Analysis of Low Birth Weight and Preterm Delivery among Australian Women.

OBJECTIVES: To identify patterns of health, socioeconomic, behavioral, and psychosocial indicators that may be associated with low birth weight delivery or preterm birth. STUDY DESIGN: Data were analyzed from the Australian Longitudinal Study on Women's Health. A total of 9075 live singleton births among 3801 women were linked to state perinatal records with birth outcome data. Survey data were used to identify 11 indicators for latent class analysis. Latent classes were tested for association to birth outcomes. These indicators also were used along with covariates in main effect multiple logistic regression analyses of birth outcomes. RESULTS: Latent class analysis revealed 5 classes, including those characterized by low education, recent drug use, stress/anxiety/depression, smoking/drinking/low education/multi-risk, and a low risk referent group. The stress/anxiety/depression class was associated with preterm delivery (OR 1.87, 95% CI 1.20-2.92), and the smoking/drinking/low education/multirisk class was associated with low birth weight (OR 1.54, 95% CI 1.02-2.30). Traditional logistic regression analyses for main effects identified some measures not captured by the latent classes, and the latent classes identified variable combinations not captured by the main effect analysis. CONCLUSIONS: Unique latent classes were associated with preterm delivery vs low birth weight. Both latent class analysis and main effects analyses may be combined to improve understanding of birth outcome risks. Clinical and programmatic interventions to reduce risks of low birth weight and preterm delivery may benefit from risk profiles that women experience.

Association between Thyroid Function and Exposures to Brominated and Organophosphate Flame Retardants in Rural Central Appalachia.

Exposure to flame retardants (FRs) is associated with adverse effects on human health. Focusing on three FR groups, including polybrominated diphenyl ethers (PBDEs), organophosphate FRs (OPFRs), and novel brominated FRs (nBFRs), we determined the levels of these chemicals in indoor air in homes in rural Central Appalachia using passive air samplers and personal exposures in the residents of these homes using silicone wristbands. We also investigated the relationships between the FR levels in wristbands and the thyroid function. The median total concentrations of PBDEs, OPFRs, and nBFRs were 210, 25 000, and 69 pg/m3 in indoor air, and 49, 670, and 110 ng/g in wristbands, respectively. The most abundant chemicals in both air and wristbands were BDE-47 and -99 among PBDEs, tris[(2R)-1-chloro-2-propyl] phosphate among OPFRs, and 2-ethylhexyl 2,3,4,5-tetrabromobenzoate and bis(2-ethylhexyl) tetrabromophthalate among nBFRs. In gender-specific regression models that were controlled for age and smoking, significant associations were observed between BDE-99, BDE-197, and 2-ethylhexyldiphenyl phosphate (EHDP) and free thyroxine (FT4), between BDE-100 and free triiodothyronine (FT3), and between anti-Dechlorane Plus (DP) and thyroid-stimulating hormone (TSH). In particular, most penta-BDE congeners were significantly or marginally significantly associated with FT4 and FT3 for both females and males. Our results suggest that wristbands can be used as suitable exposure monitors for evaluating human exposure to FRs.

Metal mixtures and kidney function: An application of machine learning to NHANES data.

BACKGROUND: Exposure to heavy metals may increase risk of kidney disease, but most studies have examined individual metals or two-way interactions. There is increasing recognition of the importance of studying exposure to metal mixtures and health outcomes. OBJECTIVES: We used Bayesian kernel machine regression (BKMR) to examine associations between a mixture of four heavy metals and indicators of kidney function. METHODS: We used NHANES 2015-16 data on 1435 adults aged 40 and over to study cross-sectional associations between blood levels of four heavy metals (Co, Cr, Hg and Pb) and kidney function. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and by albumin to creatinine ratio (ACR), measured continuously and dichotomized into indicators of chronic kidney disease (CKD) and albuminuria, respectively. BKMR tested for non-linearity in the exposure-specific responses to evaluate dose-response relationships between mixtures and outcomes and possible interaction effects among exposures. Interactions among continuous outcomes were identified using the NLinteraction package in R. RESULTS: A higher metals mixture was significantly associated with all four measures of kidney function in dose-response patterns. Pb had the strongest association with eGFR, albuminuria and ACR, and the second strongest association with CKD. We also observed an interaction between Pb and Co for eGFR and an interaction between Pb and Cd for ACR. CONCLUSIONS: Exposure to a co-occurring heavy metals mixture was associated with indicators of poor kidney function. Within this mixture, Pb, Co and Cd considered singly and jointly made the greatest contributions to the observed effects. Future prospective study is needed to confirm the association between metal mixtures and kidney function.

Lifestyle and Psychosocial Patterns and Diabetes Incidence Among Women with and Without Obesity: a Prospective Latent Class Analysis.

We conducted latent class analyses to identify women with homogeneous combinations of lifestyle and behavioral variables and tested whether latent classes were prospectively associated with diabetes incidence for women with or without baseline obesity. A total of 64,710 postmenopausal women aged 50-79 years without prevalent diabetes at baseline (years 1993-1998) were followed until 2018 with a mean follow-up of 14.6 years (sd = 6.4). Lifestyle variables included smoking, diet quality, physical activity, and sleep quality. Psychosocial variables included social support, depression, and optimism. Multivariable Cox proportional hazards regression models tested associations between latent classes and diabetes incidence controlling for age, race/ethnicity, and education. During follow-up, 8076 (12.4%) women developed diabetes. For women without baseline obesity, five latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.45; 95% CI 1.28, 1.64), poor diet and exercise (HR = 1.23; 95% CI 1.13, 1.33), and psychosocial risks alone (HR = 1.20; 95% CI 1.12, 1.29). For women with baseline obesity, four latent classes were identified. Compared with a lower risk referent, diabetes incidence was higher for women with obesity in classes characterized by high probability of multiple lifestyle and psychosocial risks (HR = 1.48; 95% CI 1.32, 1.66), poor diet and exercise (HR = 1.32; 95% CI 1.19, 1.47), and intermediate probabilities of multiple risks (HR = 1.17; 95% CI 1.05, 1.30). Diabetes prevention efforts that focus on diet and exercise may benefit from attention to how lifestyle behaviors interact with psychosocial variables to increase diabetes risks, and conversely, how psychological or social resources may be leveraged with lifestyle changes to reduce the risk for women with and without obesity.