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Lack of association between endocrine disrupting chemicals and male fertility: A systematic review and meta-analysis.
Martínez, MÁ, Marquès, M, Salas-Huetos, A, Babio, N, Domingo, JL, Salas-Salvadó, J
Environmental research. 2023;217:114942
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Exposure to natural or synthetic chemicals is directly related to environmental conditions, dietary and other lifestyle factors. Some of these chemicals are named endocrine disrupting chemicals (EDCs) because of their capability to interfere with the endocrine system. The aim of this study was to summarise and explore the association between exposure to EDCs and human male fertility indicators. This study is a systematic review and meta-analysis of seven studies; 4 assessed bisphenol A (BPA) in urine and sperm quality parameters, while 3 articles evaluated PCB153 [polychlorinated biphenyls] in serum and sperm quality parameters. Results show that there weren’t any positive or inverse associations between BPA or PCB153 and the sperm parameters analysed. Authors conclude that the systematic review showed a high disparity between studies, making difficult a consensus on the possible detrimental effect of the 12 groups of EDCs on male fertility. Thus, no conclusive statements can be drawn. Further studies are needed in order to provide more robust data.
Abstract
The incidence of infertility currently affects about 15% of the world's population. Male factors are estimated to be responsible for up to 40-50% of these cases. While the cause of these reproductive disorders is still unclear, the exposure to a family of ubiquitous compounds in our daily life, named endocrine disrupting chemicals (EDCs) could be involved. This paper was aimed at performing a systematic review and meta-analysis of population studies exploring whether human male exposure to EDCs affects male fertility. Clinical and observational studies assessing the exposure to EDCs along with sperm quality, the most common reproductive disorders, sperm DNA damage, sperm oxidative stress, fertilization rate, implantation rate, clinical pregnancy rate, live birth rate, and miscarriage rate were included. The quality assessment tool from the NHLBI-NIH was used to assure that studies met standardized quality criteria. Sensitivity analysis and heterogeneity among studies was assessed. Overall, the 32 selected articles, including 7825 individuals in the systematic review, explored 12 families of EDCs. The results revealed a high heterogeneity among studies in relation to the association between exposure to EDCs and the endpoints analyzed. Meta-analyses were performed with data from 7 articles including 479 individuals, 4 articles assessing the association between BPA in urine and sperm quality, and 3 articles evaluating PCB153 in serum and sperm quality. In the meta-analysis, we identified an unpredicted significant positive association between PCB153 exposure and sperm concentration. However, it would not be clinically relevant. No positive or inverse associations were found neither for BPA, nor for PCB153 and the rest of sperm parameters analyzed. The high disparity between studies made difficult to draw conclusions on the potential harmful effects of EDCs on male fertility. Consequently, to delineate the potential relationship that EDCs can have on male fertility, an important condition stressing the health system, further investigations are required.
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Lifestyle-, environmental-, and additional health factors associated with an increased sperm DNA fragmentation: a systematic review and meta-analysis.
Szabó, A, Váncsa, S, Hegyi, P, Váradi, A, Forintos, A, Filipov, T, Ács, J, Ács, N, Szarvas, T, Nyirády, P, et al
Reproductive biology and endocrinology : RB&E. 2023;21(1):5
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The World Health Organization defines infertility as regular unprotected sexual intercourse without achieving conception within a year. In recent years, there has been a growing demand for functional, objective parameters reflecting fertility status more clearly than classical parameters. Of these, sperm DNA fragmentation (SDF) and the DNA fragmentation index – denoting the percentage of sperm with damaged DNA – seem to be of utmost importance. The aim of this study was to investigate all risk factors that may potentially be increasing SDF. This study is a systematic review and meta-analysis of one hundred and ninety articles. The earliest studies were published in 2003, and the latest in 2021. Results show that several modifiable risk factors negatively affect SDF, namely; a. health conditions: varicocele [when veins become enlarged inside the pouch of skin that holds the testicles] and impaired glucose tolerance, b. infections: Chlamydia, c. malignancies: testicular tumours, and d. lifestyle factors: smoking, alcohol consumption and body mass index. Authors conclude that several lifestyle-, environmental-, and additional health factors are associated with increased SDF.
Abstract
INTRODUCTION Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. METHODS We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. RESULTS We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52). CONCLUSION Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. TRIAL REGISTRATION CRD42021282533.
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Effectiveness of Therapeutic Patient Education Interventions in Obesity and Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Correia, JC, Waqas, A, Huat, TS, Gariani, K, Jornayvaz, FR, Golay, A, Pataky, Z
Nutrients. 2022;14(18)
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Obesity and diabetes mellitus (DM) account for the highest burden of non-communicable diseases. Obesity is also highly comorbid with type 2 DM with a prevalence of 8.5% among adults around the globe. The aims of this study were to present (a) a critical synthesis of the theoretical basis and development of therapeutic patient education (TPE) interventions for obesity and diabetes, and (b) quantitative evidence for the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. This study is a systematic review and meta-analysis of fifty-four randomised controlled trials. Results show that: - TPE interventions bring about significant improvements in biomedical outcomes among patients with DM and obesity. - there weren’t significant differences in the quality of life of participants undergoing TPE interventions (inconclusive as only data from two studies were considered). - interventions delivered through different media and delivery formats may be equally effective. Authors conclude that the use of electronic media such as short messaging services, website-based educational programs and animation media can be used to deliver TPE effectively.
Abstract
Diabetes mellitus (DM) and obesity account for the highest burden of non-communicable diseases. There is increasing evidence showing therapeutic patient education (TPE) as a clinically and cost-effective solution to improve biomedical and psychosocial outcomes among people with DM and obesity. The present systematic review and meta-analysis present a critical synthesis of the development of TPE interventions for DM and obesity and the efficacy of these interventions across a range of biomedical, psychosocial and psychological outcomes. A total of 54 of these RCTs were identified among patients with obesity and diabetes and were thus qualitatively synthesized. Out of these, 47 were included in the quantitative synthesis. There was substantial heterogeneity in the reporting of these outcomes (I2 = 88.35%, Q = 317.64), with a significant improvement noted in serum HbA1c levels (standardized mean difference (SMD) = 0.272, 95% CI: 0.118 to 0.525, n = 7360) and body weight (SMD = 0.526, 95% CI: 0.205 to 0.846, n = 1082) in the intervention group. The effect sizes were comparable across interventions delivered by different modes and delivery agents. These interventions can be delivered by allied health staff, doctors or electronically as self-help programs, with similar effectiveness (p < 0.001). These interventions should be implemented in healthcare and community settings to improve the health outcomes in patients suffering from obesity and DM.
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Menstruation-Related Disorders-Dysmenorrhea and Heavy Bleeding-as Significant Epiphenomena in Women With Rheumatic Diseases.
Orlandi, M, Vannuccini, S, El Aoufy, K, Melis, MR, Lepri, G, Sambataro, G, Bellando-Randone, S, Guiducci, S, Cerinic, MM, Petraglia, F
Frontiers in pharmacology. 2022;13:807880
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Rheumatic diseases (RDs) affect significantly more women than men, and for this reason, gynaecological disorders may have an additional negative impact on women’s health. The aim of this study was to describe gynaecological symptoms among fertile age women with RDs and their impact on quality of life. This study is a monocentric, cross-sectional observational study. Results show that a large number of women with RDs report menstrual disorders. In fact, more than half of the population reported of having dysmenorrhea since adolescence. Similarly, during fertile age, menstrual pain was frequently reported, and in 72% of the cases, the intensity resulted to be moderate/severe. Additionally, heavy menstrual bleeding was found in 38% of the patients during adulthood and in 52% of patients during adolescence. Authors conclude that the management of female patients with RDs is a challenge for clinicians and should include an accurate evaluation of gynaecological aspects (menstruation, fertility, maternity, and sexuality) as well as manage an interdisciplinary teamwork approach (rheumatologist and gynaecologists).
Abstract
Background: In women with rheumatic diseases (RDs) menstruation-related disorders have never been investigated. The aim of this study was to evaluate gynecological symptoms/disorders in fertile age women with RDs. Materials and methods: All patients (n = 200) filled up a self-administered questionnaire on their gynecological history, menstrual cycle pattern, menstrual-related symptoms, and quality of life (QoL). The RD group was then compared to a control group of 305 age-matched fertile age women. Results: Among patients with RDs, 58% had arthritis, 40% connective tissue diseases (CTDs), and 1.5% systemic vasculitis. No differences were observed between CTDs and arthritis, except for a family history of HMB which was more common among women with CTDs (p < .01). When compared to controls, women with RDs reported more frequent heavy menstrual bleeding (HMB) during adolescence (51.7 and 25.4%, respectively; p = .0001) and adult life (37.7 and 25.9%, respectively; p = .0065). Also, dysmenorrhea in adolescence was significantly more common among cases (55.6 and 45.4%, respectively; p = .0338). Gynecological pain (dysmenorrhea, non-menstrual pelvic pain, dyspareunia, dysuria, and dyschezia) in patients with RDs was more frequent than in controls (p = .0001, .0001, .0001, .0001, .0002, respectively). Considering women who reported moderate and severe symptoms in RDs, dysmenorrhea and dyspareunia remain significantly more frequent in women with RDs than in controls (p = .0001; p = .0022; respectively). QoL scores were significantly reduced in women with RDs, either in physical (p = .0001) and mental domains (p = .0014) of short-form 12. Conclusion: Women affected by RDs frequently presented menstruation-related disorders; thus, female patients with RDs should be questioned about gynecological symptoms and referred to the gynecologist for an accurate evaluation.
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Towards a deeper understanding of the vaginal microbiota.
France, M, Alizadeh, M, Brown, S, Ma, B, Ravel, J
Nature microbiology. 2022;7(3):367-378
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The vaginal microbiota of reproductive-age cisgender women is often dominated by a single species of Lactobacillus and this is associated with good vaginal health. This review looks at the current understanding of the vaginal microbiota and its connection with host health. Women with vaginal microbiota that are not dominated by Lactobacillus species are often diagnosed with bacterial vaginosis (BV). They have an increased risk for sexually transmitted infections (STI), spontaneous preterm birth, prevalence of human papillomavirus (HPV), increased risk for cervical cancer, urinary tract infections and pelvic inflammatory disease. Factors that affect the vaginal microbiota composition are race, age, pre puberty and menopause where levels of circulating oestrogen are lower. Efforts to modulate the vaginal microbiota with antibiotics, oestrogen therapy, lactic or boric acid and vaginal probiotics have not been that successful. Vaginal microbiota transplants (VMT) are a potential approach to treat recurrent BV but further studies are needed.
Abstract
The human vaginal microbiota is a critical determinant of vaginal health. These communities live in close association with the vaginal epithelium and rely on host tissues for resources. Although often dominated by lactobacilli, the vaginal microbiota is also frequently composed of a collection of facultative and obligate anaerobes. The prevalence of these communities with a paucity of Lactobacillus species varies among women, and epidemiological studies have associated them with an increased risk of adverse health outcomes. The mechanisms that drive these associations have yet to be described in detail, with few studies establishing causative relationships. Here, we review our current understanding of the vaginal microbiota and its connection with host health. We centre our discussion around the biology of the vaginal microbiota when Lactobacillus species are dominant versus when they are not, including host factors that are implicated in shaping these microbial communities and the resulting adverse health outcomes. We discuss current approaches to modulate the vaginal microbiota, including probiotics and vaginal microbiome transplants, and argue that new model systems of the cervicovaginal environment that incorporate the vaginal microbiota are needed to progress from association to mechanism and this will prove invaluable for future research.
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The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
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SARS-CoV-2 effects on sperm parameters: a meta-analysis study.
Xie, Y, Mirzaei, M, Kahrizi, MS, Shabestari, AM, Riahi, SM, Farsimadan, M, Roviello, G
Journal of assisted reproduction and genetics. 2022;39(7):1555-1563
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Infertility is a reproductive system disorder. Viruses as a major cause of fertility problems can potentially interfere with reproductive function in men. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to be the causing viral pathogen of COVID-19 and capable of affecting human health. The aim of this study was to evaluate the effects of SARS-CoV-2 on different semen parameters including sperm count, sperm concentration, volume, motility, and progressive motility. This study is a meta-analysis of twelve studies of which seven were case control studies and five were retrospective cohort studies. Results show that SARS-CoV-2 infection could lead to significant impairments of male reproductive function through exerting negative influences on different semen parameters namely semen volume, sperm concentration, sperm count, and sperm motility. Authors conclude that their findings revealed the vulnerability of semen quality to SARS-CoV-2 infection.
Abstract
AIM: The rapid outbreak of the coronavirus disease 2019 (COVID-19) pandemic posed challenges across different medical fields, especially reproductive health, and gave rise to concerns regarding the effects of SARS-CoV-2 on male infertility, owing to the fact that the male reproductive system indicated to be extremely vulnerable to SARS-CoV-2 infection. Only a small number of studies have investigated the effects of SARS-CoV-2 on male reproduction, but the results are not consistent. So, we performed this meta-analysis to draw a clearer picture and evaluate the impacts of COVID-19 on male reproductive system. METHOD We searched Embase, Web of Science, PubMed, and Google Scholar databases to identify the potentially relevant studies. Standardized mean difference (SMD) with 95% confidence interval (CI) was applied to assess the relationship. Heterogeneity testing, sensitivity analysis, and publication bias testing were also performed. RESULTS A total of twelve studies including 7 case control investigations and 5 retrospective cohort studies were found relevant and chosen for our research. Our result showed that different sperm parameters including semen volume [SMD = - 0.27 (- 0.46, - 1.48) (p = 0.00)], sperm concentration [SMD = - 0.41 (- 0.67, - 0.15) (p = 0.002)], sperm count [SMD = - 0.30 (- 0.44, - 0.17) (p = 0.00)], sperm motility [SMD = - 0.66 (- 0.98, - 0.33) (p = 0.00)], and progressive motility [SMD = - 0.35 (- 0.61, - 0.08) (p = 0.01)] were negatively influenced by SARS-CoV-2 infection. However, sperm concentration (p = 0.07) and progressive motility (p = 0.61) were not found to be significantly associated with SARS-CoV-2 infection in case control studies. No publication bias was detected. CONCLUSION The present study revealed the vulnerability of semen quality to SARS-CoV-2 infection. Our data showed a strong association of different sperm parameters with SARS-CoV-2 infection. The results suggested that SARS-CoV-2 infection in patients may negatively influence their fertility potential in a short-term period, but more studies are needed to decide about the long-term effects.
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Effect of vitamin E on Semen Quality Parameters: A Meta-Analysis of a Randomized Controlled Trial.
Wang, R, Wang, S, Song, Y, Zhou, H, Pan, Y, Liu, L, Niu, S, Liu, X
Urology journal. 2022;19(5):343-351
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The incidence of male infertility is increasing year by year. The mechanism of male infertility is complex. One of the important causes of male infertility is the decline in semen quality. The aim of this study was to evaluate the effectiveness of oral vitamin E in improving semen quality. This study is a meta-analysis of eight articles with a total of 459 patients, including 238 cases in the experimental group and 221 cases in the control group. Results show that oral vitamin E treatment could significantly increase the total sperm count and reduce the volume of semen. It was further found that oral vitamin E treatment for up to 6 months could improve the forward motility of sperm but not for 3 months. Authors conclude that vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients.
Abstract
PURPOSE To explore the effectiveness of vitamin E in male infertility, a systematic review and meta-analysis was conducted. MATERIALS AND METHODS The retrieval time was from January 1947 to May 2021, without language restriction. Stata 12.0 was used for the meta-analysis. RESULTS A total of 8 randomized controlled trials involving 459 patients were included. The results showed that after vitamin E treatment, semen volume was reduced (95% CI: - 0.55 to - 0.06, SMD = - 0.30, p = 0.015), total sperm count was increased (95% CI: 0.02-0.45, SMD = 0.23, p = 0.035), and the differences were statistically significant. There were no statistically significant differences in increasing sperm concentration (95% CI: -0.21-0.29, SMD = 0.04, p = 0.769), total sperm motility (95% CI: -0.01-0.42, SMD = 0.20, p = 0.061) or sperm forward motility rate (95% CI: -0.06-0.65, SMD = 0.29, p = 0.106). Subgroup analysis showed that vitamin E treatment for six months could improve sperm forward motility (95% CI: 0.46-1.14, SMD = 0.80, p <0.001). CONCLUSION Vitamin E could increase the total sperm count and reduce the volume of semen in male infertility patients, and long-term treatment could improve the forward motility rate of sperm. The decrease of semen volume may be the result of different abstinence time before and after the test.
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Cadmium exposure and risk of diabetes and prediabetes: A systematic review and dose-response meta-analysis.
Filippini, T, Wise, LA, Vinceti, M
Environment international. 2022;158:106920
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Cadmium is a toxic metal released in the environment after both natural and anthropogenic activities, particularly in contaminated and industrial areas devoted to smelting and refining of metals, and the manufacturing of batteries, coatings, or plastics. Exposure to cadmium may occur through occupational activities, smoking, food, and air pollution. The aim of this study was to provide updated literature on cadmium exposure and the risk of both type 2 diabetes and prediabetes, and to model the shape of these associations using a dose response approach. This study is a systematic review and meta-analysis of forty-two studies. Diabetes was investigated as an outcome in thirty-one studies, prediabetes in four studies, and both diabetes and prediabetes in seven studies. Results show that higher cadmium exposure was associated with increased risks of both diabetes and prediabetes. Diabetes risk increased linearly in studies using urinary cadmium concentrations, while disease risk increased only at the highest exposure levels when assessed using blood concentrations. The analysis for prediabetes also showed a linear increase in risk from low exposure, with a flattening effect at higher urinary cadmium concentrations. Authors conclude that their findings add to the available evidence on potential adverse health effects of environmental exposure to cadmium.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Cadmium exposure through diet, occupational exposure and smoking may increase the risk of type 2 diabetes in affected individuals.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background
Cadmium exposure might occur through occupational activities, food, air pollution, and smoking. Smokers, in particular, have higher blood cadmium concentrations than non-smokers. Food is the main transmission route for non-smokers, particularly cereals, vegetables, mollusks, and offal. Females and older adults are at a greater risk due to an increased risk of iron deficiency in these population groups, leading to increased absorption, as well as greater age-related bioaccumulation.
Furthermore, cadmium exposure has been associated with an increased risk of diabetes in a number of studies, as referenced in the present manuscript. However, the magnitude and shape of the correlation are uncertain.This systematic review and meta-analysis therefore investigates the relationship between exposure to cadmium and type 2 diabetes and prediabetes risk.
Methods
- The systematic review was conducted and reported in line with the PRISMA 2020 statement. Search strings related to the terms “cadmium” and “diabetes”, or “prediabetes state” in PubMed/MEDLINE, Web of Science and EMBASE databases were employed to search for relevant articles. Latest search date: 1 October 2021.
- Eligibility criteria included: studies evaluating cadmium exposure via biomarker levels with outcomes of interest being type 2 diabetes or prediabetes using WHO criteria and the American Diabetes Association; and reporting of relative risk estimates using the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) with the corresponding 95% confidence interval (CIs). For inclusion in dose-response meta-analysis: reported effect estimates for all exposure categories along with dose in each category.
- Studies were assessed for risk of bias using theROBINS-E tool. Overall certainty of the evidence was assessed using the GRADE approach.
- The meta-analysis involved estimating RRs with corresponding 95% CIs from each study. Generalised least-squares regression with a random effects model and restricted maximum likelihood estimation were used. The highest versus lowest exposure categories were compared. The association between exposure and risk of diabetes or prediabetes was investigated using a one-stage dose-response meta-analysis. Sensitivity analyses were performed and heterogeneity between studies was assessed..
Results
- 42 eligible studies (case-control, cross-sectional, and cohort studies), ranging 65-34, 814 male and female adult participants, were identified investigating the association between cadmium exposure and risk of diabetes or prediabetes. Seven of the included studies were at overall high risk of bias; heterogeneity in the resulting meta-analyses was moderate to substantial. Sensitivity analyses indicated comparable results. Assessment with GRADE found no major inconsistency, indirectness or imprecision for either outcome.
- Comparing the highest versus lowest cadmium exposure concentrations associated with type 2 diabetes resulted in a RR of 1.24 (95% CI 0.96–1.59), RR 1.21 (CI 95% 1.00–1.45), and RR 1.47 (CI 95% 1.01–2.13) for blood, urinary, and toenail matrices, respectively. Concurrently, there was an elevated risk of prediabetes for cadmium levels in urine of RR 1.41 (95% CI: 1.15–1.73) and blood RR 1.38 (95% CI: 1.16–1.63), respectively.
- In the dose-response meta-analysis, a linear positive correlation between increasing urinary cadmium levels and diabetes risk was observed, with a RR 1.25 (95% CI 0.90–1.72) at concentration 2.0 µg/g of creatinine compared with no exposure. Conversely, for blood cadmium concentrations, the diabetes risk seemed to rise above 1 µg/L compared with no exposure. Moreover, prediabetes risk increased up to approximately 2 µg/g creatinine beyond which a plateau was reached with RR 1.40 (95% CI 1.12–1.76) at 2 µg/g creatinine.
- The meta-regression showed a negligible correlation between blood cadmium levels and diabetes risk. However, a positive yet imprecise association was found with increasing urinary cadmium concentrations. Similarly, no association was observed between blood cadmium concentrations and risk of prediabetes, whereas a positive relationship with urinary cadmium levels was observed. However, these findings were based on a limited cohort of studies.
Conclusions
- A positive linear correlation between cadmium concentration (measured in multiple matrices) and risk of both type 2 diabetes and prediabetes with a dose-response relationship (moderate-certainty evidence) were observed in this systematic review and meta-analysis. Diabetes risk increased linearly in studies using urinary cadmium concentrations, whereas disease risk increased only at the highest exposure levels when assessed using blood levels. The analysis for prediabetes also demonstrated a linear increase in risk from low exposure, which plateaued at higher urinary cadmium concentrations.
Clinical practice applications:
- To inform practitioners and clients of the risks of cadmium exposure in the diet, through occupational exposure, and through smoking.
- To motivate practitioners to educate themselves and their clients regarding the foods which may pose a higher risk of cadmium exposure (not reviewed in the present article).
- To advise clients on prediabetes and type 2 diabetes risk from cadmium exposure through smoking.
Considerations for future research:
- As cited by the authors, future studies could incorporate stratified analysis in specific subgroups, e.g., non-smokers, or could be restricted to prospective cohort studies with more sufficient data,
- Large-scale observational studies could be conducted investigating cadmium exposure in smokers versus non-smokers.
- Clinical trials could be performed to evaluate the effect of reduction or cessation of tobacco smoking on total body cadmium concentrations .
- Continuous surveillance of dietary cadmium exposure and other heavy metals should be prioritised to inform public health.
- Dietary interventions could assess the possibility to attenuate the risk of cadmium exposure.
Abstract
BACKGROUND 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. OBJECTIVE 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. DATA SOURCE 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. STUDY ELIGIBILITY CRITERIA 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. STUDY APPRAISAL AND SYNTHESIS METHODS 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. RESULTS 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. LIMITATIONS AND CONCLUSIONS This analysis provides moderate-certainty evidence for a positive association between cadmium exposure (measured in multiple matrices) and risk of both diabetes and prediabetes.
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Evidence on Human Exposure to Pesticides and the Occurrence of Health Hazards in the Brazilian Population: A Systematic Review.
Panis, C, Kawassaki, ACB, Crestani, APJ, Pascotto, CR, Bortoloti, DS, Vicentini, GE, Lucio, LC, Ferreira, MO, Prates, RTC, Vieira, VK, et al
Frontiers in public health. 2021;9:787438
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The use of pesticides to eradicate pests is a common agricultural practice. Between 2009 and 2019, Brazilians used more chemicals to eradicate weeds, fungi, and insects. Brazil is a heavy user of pesticides, but their toxic effects, including their health and environmental effects, have not been well studied. A total of 44 studies are included in this systematic review. There is a link between pesticide exposure and neurological damage, cancer, gastrointestinal issues, poisoning, hormonal irregularities, and malformations in children, according to the studies included in this review. The systematic review shows that pesticides are toxic to both rural and urban workers regardless of their age and gender. For a comprehensive assessment of pesticides' toxic effects on the environment and human health, more robust research is needed. Despite this, healthcare professionals can use the research findings to identify pesticide health impacts and make informed clinical decisions.
Abstract
Brazil is among the biggest pesticide consumers in the world, with its population severely exposed to tons of such substances, both because of environmental contamination and occupational use. The health consequences of pesticide exposure are well-documented, but still sparse regarding Brazilian population. This study systematically reviewed the Brazilian studies published that address the relationship between exposure to pesticides and health problems in the Brazilian population. Also, information about pesticide use in Brazil is provided. The included studies showed that exposure to pesticides has a relevant impact on the health of the Brazilian population, regardless of age and gender, and on workers in rural areas or not. Most poisoning events seem to result from the continuous use of pesticides, whether occupationally or environmentally, characterizing a public health problem. The major consequences reported in literature were damage to the central nervous system, cancer, deleterious effects on rural workers' health, intoxications, malformations, and endocrine changes. These findings point out the need to understand the impact of chronic exposure to pesticides on severely exposed people and highlight the importance of creating public policies to protect them and avoid disease occurrence.