•Blood and urinary cadmium is linearly associated with type 2 diabetes risk.•Diabetes risk starts to increase above 1 µg/L of blood cadmium levels.•Prediabetes risk increases up to 2 µg/g of ...creatinine, then reaches a plateau.
Cadmium exposure has been associated with increased diabetes risk in several studies, though there is still considerable debate about the magnitude and shape of the association.
To perform a systematic review and meta-analysis of observational studies investigating the relation between cadmium exposure and risk of type 2 diabetes and prediabetes, and to summarize data on the magnitude and shape of the association.
After conducting an online literature search through October 1, 2021, we identified 42 eligible studies investigating the association between cadmium exposure and risk of diabetes and prediabetes.
We included studies that assessed cadmium exposure through biomarker levels; examined type 2 diabetes or prediabetes among outcomes; and reported effect estimates for cadmium exposure for meta-analysis only.
Studies were evaluated using ROBINS-E risk of bias tool. We quantitively assessed the relation between exposure and study outcomes using one-stage dose-response meta-analysis with a random effects meta-analytical model.
In the meta-analysis, comparing highest-versus-lowest cadmium exposure levels, summary relative risks (RRs) for type 2 diabetes were 1.24 (95% confidence interval 0.96–1.59), 1.21 (1.00–1.45), and 1.47 (1.01–2.13) for blood, urinary, and toenail matrices, respectively. Similarly, there was an increased risk of prediabetes for cadmium concentrations in both urine (RR = 1.41, 95% CI: 1.15–1.73) and blood (RR = 1.38, 95% CI: 1.16–1.63).
In the dose-response meta-analysis, we observed a consistent linear positive association between cadmium exposure and diabetes risk, with RRs of 1.25 (0.90–1.72) at 2.0 µg/g of creatinine. Conversely for blood cadmium, diabetes risk appeared to increase only above 1 µg/L. Prediabetes risk increased up to approximately 2 µg/g creatinine above which it reached a plateau with RR of 1.42 (1.12–1.76) at 2 µg/g creatinine.
This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
Purpose of Review
Selenium, a trace element, is ubiquitous in the environment. The main source of human exposure is diet. Despite its nutritional benefits, it is one of the most toxic naturally ...occurring elements. Selenium deficiency and overexposure have been associated with adverse health effects. Its level of toxicity may depend on its chemical form, as inorganic and organic species have distinct biological properties.
Recent Findings
Nonexperimental and experimental studies have generated insufficient evidence for a role of selenium deficiency in human disease, with the exception of Keshan disease, a cardiomyopathy. Conversely, recent randomized trials have indicated that selenium overexposure is positively associated with type 2 diabetes and high-grade prostate cancer. In addition, a natural experiment has suggested an association between overexposure to inorganic hexavalent selenium and two neurodegenerative diseases, amyotrophic lateral sclerosis and Parkinson’s disease.
Summary
Risk assessments should be revised to incorporate the results of studies demonstrating toxic effects of selenium. Additional observational studies and secondary analyses of completed randomized trials are needed to address the uncertainties regarding the health risks of selenium exposure.
Accumulating evidence from both experimental and nonexperimental human studies in the last 15 years indicates that exposure to high levels of the trace element selenium increases the risk of type 2 ...diabetes. However, the relation of dose to effect is not well understood because randomized controlled trials used only one dose (200 μg/day) of selenium supplementation. While no new trial on this topic has been published since 2018, several nonexperimental studies have appeared. We therefore updated a previous meta-analysis to include recently published observational studies, and incorporated the recently developed one-stage random-effects model to display the dose-response relation between selenium and type 2 diabetes. We retrieved 34 potentially eligible nonexperimental studies on selenium and diabetes risk up to April 15, 2021. The bulk of the evidence indicates a direct relation between blood, dietary and urinary levels of selenium and risk of diabetes, but not with nail selenium, which may be considered a less reliable biomarker. The association was nonlinear, with risk increasing above 80 μg/day of dietary selenium. Whole blood/plasma/serum selenium concentrations of 160 μg/L corresponded to a risk ratio of 1.96 (95% CI 1.27–3.03) compared with a concentration of 90 μg/L (approximately 60 μg of daily selenium intake). The cohort studies, which are less susceptible to reverse causation bias, indicated increased risk for both blood and urine selenium levels and dietary selenium intake, whereas no such pattern emerged from studies relying on nail selenium content. Overall, the nonexperimental studies agree with findings from randomized controlled trials, indicating that moderate to high levels of selenium exposure are associated with increased risk for type 2 diabetes.
•We performed a dose-response assessment between Se exposure and type 2 diabetes.•We found a direct relation between blood, dietary and urinary Se with diabetes risk.•Positive relation with diabetes arose particularly above 60–80 μg/day of Se intake.•Findings were confirmed in cohort studies, less susceptible to reverse causation.
Recent evidence from laboratory and epidemiologic studies has shed a different light on selenium health effects and its recommended range of environmental exposure, compared with earlier research. ...Specifically, epidemiologic studies in Western populations have shown adverse effects of selenium exposure at low levels, sometimes below or slightly above selenium intakes needed to maximize selenoprotein expression and activity. In addition, three recent lines of evidence in molecular and biochemical studies suggest some potential drawbacks associated with selenoprotein maximization: 1) the possibility that selenoprotein upregulation is a compensatory response to oxidative challenge, induced by selenium itself or other oxidants; 2) the capacity of selenoproteins to trigger tumor growth in some circumstances; and 3) the deleterious metabolic effects of selenoproteins and particularly of selenoprotein P. The last observation provides a toxicological basis to explain why in humans selenium intake levels as low as 60 μg/day, still in the range of selenium exposure upregulating selenoprotein expression, might start to increase risk of type 2 diabetes. Overall, these new pieces of evidence from the literature call into question the purported benefit of selenoprotein maximization, and indicate the need to reassess selenium dietary reference values and upper intake level. This reassessment should clarify which range of selenoprotein upregulation follows restoration of adequate selenium availability and which range is driven by a compensatory response to selenium toxicity and oxidative stress.
•Recent epidemiologic and laboratory studies have shed a new light on selenium.•Environmental selenium may have adverse effects at levels previously considered to be safe.•Selenoprotein maximization can be associated with drawbacks in humans.•The reassessment of dietary reference values for selenium is warranted.
Uterine leiomyomata (UL) have a substantial impact on women's health, but relatively few studies have identified opportunities for primary prevention of these neoplasms. Most established risk factors ...are not modifiable, including premenopausal age, African ancestry, age at menarche, and childbearing history. The main challenge in studying UL is that a large proportion of tumors are asymptomatic. Herein, we review the epidemiology of UL from published studies to date. We highlight the advantages of ultrasound screening studies and the ways in which their innovative methods have helped clarify the etiology of disease. We conclude with a discussion of promising new hypotheses.
There is a growing literature investigating the effects of selenium on the central nervous system and cognitive function. However, little is known about the role of selenoprotein P, the main selenium ...transporter, which can also have adverse biological effects. We conducted a prospective cohort study of individuals aged 42-81 years who received a clinical diagnosis of mild cognitive impairment. Using sandwich ELISA methods, we measured full-length selenoprotein P concentrations in serum and cerebrospinal fluid to assess the relation with dementia incidence during a median follow-up of 47.3 months. We used Cox proportional hazards regression and restricted cubic splines to model such relation. Of the 54 participants, 35 developed dementia during follow-up (including 26 cases of Alzheimer's dementia). Selenoprotein P concentrations in serum and cerebrospinal fluid were highly correlated, and in spline regression analyses they each showed a positive non-linear association with dementia risk, particularly after excluding dementia cases diagnosed within 24 months of follow-up. We also observed differences in association according to the dementia subtypes considered. Risk ratios of dementia peaked at 2-6 at the highest levels of selenoprotein P, when compared to its median level, also depending on matrix, analytical methodology and dementia subtype. Findings of this study, the first to assess selenoprotein P levels in the central nervous system in vivo and the first to use a prospective study design to evaluate associations with dementia, suggest that higher circulating concentrations of selenoprotein P, both in serum and cerebrospinal fluid, predict progression of MCI to dementia. However, further confirmation of these findings is required, given the limited statistical precision of the associations and the potential for residual confounding.
Abstract
Breast cancer is the most common malignancy in women and the second leading cause of cancer death overall. Besides genetic, reproductive, and hormonal factors involved in disease onset and ...progression, greater attention has focused recently on the etiologic role of environmental factors, including exposure to artificial lighting such as light-at-night (LAN). We investigated the extent to which LAN, including outdoor and indoor exposure, affects breast cancer risk. We performed a systematic review of epidemiological evidence on the association between LAN exposure and breast cancer risk, using a dose–response meta-analysis to examine the shape of the relation. We retrieved 17 eligible studies through September 13, 2021, including ten cohort and seven case–control studies. In the analysis comparing highest versus lowest LAN exposure, we found a positive association between exposure and disease risk (risk ratio RR 1.11, 95% confidence interval-CI 1.07–1.15), with comparable associations in case–control studies (RR 1.14, 95% CI 0.98–1.34) and cohort studies (RR 1.10, 95% CI 1.06–1.15). In stratified analyses, risk was similar for outdoor and indoor LAN exposure, while slightly stronger risks were observed for premenopausal women (premenopausal: RR 1.16, 95% CI 1.04–1.28; postmenopausal: 1.07, 95% CI 1.02–1.13) and for women with estrogen receptor (ER) positive breast cancer (ER + : RR 1.09, 95% CI 1.02–1.17; ER–: RR 1.07, 95% CI 0.92–1.23). The dose–response meta-analysis, performed only in studies investigating outdoor LAN using comparable exposure assessment, showed a linear relation up to 40 nW/cm
2
/sr after which the curve flattened, especially among premenopausal women. This first assessment of the dose–response relation between LAN and breast cancer supports a positive association in selected subgroups, particularly in premenopausal women.
Does preimplantation genetic testing for aneuploidy (PGT-A) increase the likelihood of live birth among women undergoing autologous IVF who have fertilized embryos?
PGT-A is associated with a greater ...probability of live birth among women 35 years old and older who are undergoing IVF.
Previous studies evaluating the association between PGT-A and the incidence of live birth may be prone to confounding by indication, as women whose embryos undergo PGT-A may have a lower probability of live birth due to other factors associated with their increased risk of aneuploidy (e.g. advancing age, history of miscarriage). Propensity score matching can reduce bias where strong confounding by indication is expected.
We conducted a retrospective cohort study utilizing data from women who underwent autologous IVF treatment, had their first oocyte retrieval at our institution from 1 January 2011 through 31 October 2017 and had fertilized embryos from this retrieval. If a woman elected to use PGT-A, all good quality embryos (defined as an embryo between Stages 3 and 6 with Grade A or B inner or outer cell mass) were tested. We only evaluated cycles associated with the first oocyte retrieval in this analysis.
Our analytic cohort included 8227 women. We used multivariable logistic regression to calculate a propensity score for PGT-A based on relevant demographic and clinical factors available to the IVF provider at the time of PGT-A or embryo transfer. We used the propensity score to match women who did and did not utilize PGT-A in a 1:1 ratio. We then used log-binomial regression to compare the cumulative incidence of embryo transfer, clinical pregnancy, miscarriage and live birth between women who did and did not utilize PGT-A. Because the risk of aneuploidy increases with age, we repeated these analyses among women <35, 35-37 and ≥38 years old based on the Society for Assisted Reproductive Technology's standards.
Overall, women with fertilized embryos who used PGT-A were significantly less likely to have an embryo transfer (risk ratios (RR): 0.78; 95% CI: 0.73, 0.82) but were more likely to have a cycle that resulted in a clinical pregnancy (RR: 1.15; 95% CI: 1.04, 1.28) and live birth (RR: 1.21; 95% CI: 1.08, 1.35) than women who did not use PGT-A. Among women aged ≥38 years, those who used PGT-A were 67% (RR: 1.67; 95% CI: 1.31, 2.13) more likely to have a live birth than women who did not use PGT-A. Among women aged 35-37 years, those who used PGT-A were also more likely to have a live birth (RR: 1.27; 95% CI: 1.05, 1.54) than women who did not use PGT-A. In contrast, women <35 years old who used PGT-A were as likely to have a live birth (RR: 0.91; 95% CI: 0.78, 1.06) as women <35 years old who did not use PGT-A.
We were unable to abstract several potential confounding variables from patients' records (e.g. anti-Mullerian hormone levels and prior IVF treatment), which may have resulted in residual confounding. Additionally, by restricting our analyses to cycles associated with the first oocyte retrieval, we were unable to estimate the cumulative incidence of live birth over multiple oocyte retrieval cycles.
Women aged 35 years or older are likely to benefit from PGT-A. Larger studies might identify additional subgroups of women who might benefit from PGT-A.
No funding was received for this study. D.S. reports that he is a member of the Cooper Surgical Advisory Board. The other authors report no conflicts of interest.
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Exposure to toxic metals is a global public health threat. Among other adverse effects, exposure to the heavy metal cadmium has been associated with greater risk of cardiovascular disease (CVD). ...Nonetheless, the shape of the association between cadmium exposure and CVD risk is not clear. This systematic review summarizes data on the association between cadmium exposure and risk of CVD using a dose-response approach. We carried out a literature search in PubMed, Web of Science, and Embase from inception to December 30, 2023. Inclusion criteria were: studies on adult populations, assessment of cadmium exposure, risk of overall CVD and main CVD subgroups as endpoints, and observational study design (cohort, cross-sectional, or case-control). We retrieved 26 eligible studies published during 2005–2023, measuring cadmium exposure mainly in urine and whole blood. In a dose-response meta-analysis using the one-stage method within a random-effects model, we observed a positive association between cadmium exposure and risk of overall CVD. When using whole blood cadmium as a biomarker, the association with overall CVD risk was linear, yielding a risk ratio (RR) of 2.58 (95 % confidence interval-CI 1.78–3.74) at 1 μg/L. When using urinary cadmium as a biomarker, the association was linear until 0.5 μg/g creatinine (RR = 2.79, 95 % CI 1.26–6.16), after which risk plateaued. We found similar patterns of association of cadmium exposure with overall CVD mortality and risks of heart failure, coronary heart disease, and overall stroke, whereas for ischemic stroke there was a positive association with mortality only. Overall, our results suggest that cadmium exposure, whether measured in urine or whole blood, is associated with increased CVD risk, further highlighting the importance of reducing environmental pollution from this heavy metal.
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•Whole blood concentrations of cadmium are linearly associated with risk of cardiovascular disease (CVD).•Urinary concentrations of cadmium have a positive non-monotonic association with CVD risk.•Cadmium exposure appears to increase risk of heart failure, coronary heart disease, and stroke.
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