Association between urinary cadmium levels and prediabetes in the NHANES 2005-2010 population.
ABSTRACT: Evidence suggests an association between exposure to cadmium and dysglycemia. To investigate this matter, we examined the relationship between urinary cadmium and prediabetes in the cross sectional National Health and Nutrition Examination Survey (NHANES). NHANES participants for the years 2005 through 2010 aged ? 40 years were included in the analysis. Participants with nephropathy, overt diabetes, or missing required data were excluded. To assess the non-linear relationship between cadmium and Prediabetes, non-parametric logistic regression with B spline expansion of urinary cadmium/creatinine ratio was performed. This analysis revealed a complex non-linear association between higher cadmium levels and prediabetes. This relationship persisted, though with varying magnitudes across smoking groups (never smokers, moderate smokers, heavy smokers). In a conventional logistic regression analysis, this relationship was less evident with significantly increased OR for prediabetes was found in the highest quintile of urine cadmium compared to the lowest quintile in the overall population and in moderate smokers. In an age stratified analysis, a significant linear association was found only in the age groups 60-69 and ? 70. We conclude that there is a significant non-linear, complex relationship between urinary Cd levels, age, smoking habits and odds of prediabetes.
Project description:BACKGROUND: A study was undertaken to determine the relation between urinary cadmium levels and lung function in a nationally representative cohort of current, former, and never smokers in the US. Urinary cadmium levels reflect the total body burden of cadmium. METHODS: The following data from the Third National Health and Nutrition Examination Survey were analysed: urinary cadmium (adjusted for urinary creatinine), lung function, sex, race/ethnicity, age, education level, job category, body mass index, serum cotinine level, and smoking history. Linear regression models were developed to predict lung function using urinary cadmium as the main predictor, adjusting for other covariates and stratified by smoking status. RESULTS: Data were available on 16 024 adults. Current smokers had higher mean (SE) urinary cadmium/creatinine levels (0.46 (0.01) micro g/g) than former (0.32 (0.01) micro g/g) or never smokers (0.23 (0.01) micro g/g). Higher levels of urinary cadmium were associated with significantly lower forced expiratory volumes in 1 second (FEV(1)) in current (-2.06%, 95% confidence interval (CI) -2.86 to -1.26 per 1 log increase in urinary cadmium) and former smokers (-1.95%, 95% CI -2.87 to -1.03) but not in never smokers (-0.18%, 95% CI -0.60 to 0.24). Similar results were obtained for forced vital capacity (FVC) and FEV(1)/FVC. CONCLUSIONS: Cadmium, which is known to cause emphysema in occupational settings, may also be important in the development of tobacco related lung disease.
Project description:Cadmium has been linked to impaired cognitive function in adults and may cause behavioral, physiological and molecular abnormalities characteristic of Alzheimer's disease (AD) in animals. Evidence linking cadmium and AD in humans is limited, but supportive. In the most recent epidemiologic study, blood cadmium in U.S. adults was positively associated with elevated AD mortality 7-13 years later. The association between urinary cadmium - an arguably more appropriate biomarker for studying chronic diseases - and AD mortality has not yet been explored. Further study of cadmium and AD mortality in an independent population, with longer follow-up, and stratified by sex is also needed. We sought to answer these questions using the U.S. National Health and Nutrition Examination Survey (NHANES) (1999-2006 cycles) and NHANES III (interviews in 1988-1994) datasets, separately linked to AD mortality as of 2011. We used survey-weighted Cox regression models predicting age at AD death and adjusted for race/ethnicity, sex, smoking status, education and urinary creatinine. An interquartile range (IQR; IQR=0.51ng/mL) increase in urinary cadmium was associated with 58% higher rate of AD mortality (hazard ratio (HR)=1.58, 95% CI: 1.20, 2.09. p-value=0.0009, mean follow-up: 7.5 years) in NHANES 1999-2006 participants. In contrast, in NHANES III participants, an IQR (IQR=0.78ng/mL) increase in urinary cadmium was not associated with AD mortality (HR=0.85, 95% CI: 0.63, 1.17, p-value=0.31, mean follow-up: 13 years). Also in the NHANES III sample however, when the maximum follow-up time was restricted to 12.7 years (i.e. the same as NHANES 1999-2006 participants) and urinary creatinine adjustments were not made, urinary cadmium was associated with elevated AD mortality (HR=1.11, 95% CI: 1.02, 1.20, p-value=0.0086). Our study partially supported an association between cadmium and AD mortality, but the sensitivity of results to follow-up time and creatinine adjustments necessitate cautious interpretation of the association. Further studies, particularly those on toxicological mechanisms, are required to fully understand the nature of the "cadmium-AD mortality" association.
Project description:Tobacco smoking, a risk factor for several human diseases, can lead to alterations in DNA methylation. Smoking is a key source of cadmium exposure; however, there are limited studies examining DNA methylation alterations following smoking-related cadmium exposure. To identify such cadmium exposure-related DNA methylation, we performed genome-wide DNA methylation profiling using DNA samples from 50 smokers and 50 non-smokers. We found that a total of 136 CpG sites (including 70 unique genes) were significantly differentially methylated in smokers as compared to that in non-smokers. The CpG site cg05575921 in the AHRR gene was hypomethylated (? ß?>??-?0.2) in smokers, which was in accordance with previous studies. The rs951295 (within RNA gene LOC105370802) and cg00587941 sites were under-methylated by?>?15% in smokers, whereas cg11314779 (within CELF6) and cg02126896 were over-methylated by???15%. We analyzed the association between blood cadmium concentration and DNA methylation level for 50 smokers and 50 non-smokers. DNA methylation rates of 307 CpG sites (including 207 unique genes) were significantly correlated to blood cadmium concentration (linear regression P value?<?0.001). The four significant loci (cg05575921 and cg23576855 in AHRR, cg03636183 in F2RL3, and cg21566642) were under-methylated by?>?10% in smokers compared to that in non-smokers. In conclusion, our study demonstrated that DNA methylation levels of rs951295, cg00587941, cg11314779, and cg02126896 sites may be new putative indicators of smoking status. Furthermore, we showed that these four loci may be differentially methylated by cadmium exposure due to smoking.
Project description:BACKGROUND:Cadmium and lead are hazardous pollutants. OBJECTIVE:We examined the relation between serum levels of cadmium and lead and current wheeze, current asthma, and lung function in US adults. METHODS:A cross-sectional study of 13,888 adults aged 20 to 79 years in 2007-2012 National Health and Nutrition Examination Survey (NHANES) was considered. Multivariable logistic or linear regression was used for the analyses of current wheeze, current asthma, and lung function measures (forced expiratory volume in 1 second [FEV1]% predicted, forced vital capacity [FVC]% predicted, FEV1/FVC% predicted, and fractional exhaled nitric oxide [FeNO]), which were conducted first in all participants, and then separately in never/former smokers and current smokers. RESULTS:High levels of serum cadmium were significantly associated with current wheeze in all participants and in current smokers (odds ratio for fourth vs first quartile = 2.84, 95% confidence interval = 2.07-3.90, Pfor linear trend < .01), as well as with current asthma in current smokers. Serum lead was not significantly associated with current wheeze or current asthma, regardless of smoking status. Serum cadmium was significantly associated with lower FEV1% predicted, FEV1/FVC% predicted, and FeNO in all participants and in never/former smokers, and serum lead was significantly associated with lower FEV1/FVC% predicted in all participants, with similar findings in never/former smokers and in current smokers. CONCLUSIONS:Our findings suggest that exposure to cadmium is associated with an increased risk of wheeze and asthma in US adults who currently smoke. Moreover, our results suggest that exposure to cadmium or lead has negative effects on lung function in nonsmoking US adults.
Project description:BACKGROUND:Public health policies such as tobacco control, air pollution reduction, and hazardous waste remediation may have reduced cadmium exposure among U.S. adults. However, trends in urine cadmium, a marker of cumulative cadmium exposure, have not been evaluated. OBJECTIVES:We estimated the trends in urine cadmium concentrations in U.S. adults using data from the National Health and Nutrition Examination Surveys (NHANES) from 1988 to 2008. We also evaluated the impact of changes in the distribution of available cadmium determinants (age, sex, race, education, body mass index, smoking, and occupation) at the population level to explain cadmium trends. METHODS:The study population included 19,759 adults ? 20 years of age with measures of urine cadmium and cadmium determinants. RESULTS:Age-adjusted geometric means of urine cadmium concentrations were 0.36, 0.35, 0.27, 0.27, 0.28, 0.25, and 0.26 µg/g creatinine in 1988-1991, 1991-1994, 1999-2000, 2001-2002, 2003-2004, 2005-2006, and 2007-2008, respectively. The age, sex, and race/ethnicity-adjusted percent reduction in urine cadmium geometric means comparing 1999-2002 and 2003-2008 with 1988-1994 were 27.8% (95% confidence interval: 22.3%, 32.9%) and 34.3% (29.9%, 38.4%), respectively (p-trend < 0.001), with reductions in all participant subgroups investigated. In never smokers, reductions in serum cotinine accounted for 15.6% of the observed reduction. In ever smokers, changes in smoking cessation, and cumulative and recent dose accounted for 17.1% of the observed reduction. CONCLUSIONS:Urine cadmium concentrations decreased markedly between 1988 and 2008. Declining smoking rates and changes in exposure to tobacco smoke may have played an important role in the decline of urine cadmium concentrations, benefiting both smokers and nonsmokers. Cadmium has been associated to several health outcomes in NHANES 1999-2008. Consequently, despite the observed decline, further reduction in cadmium exposure is needed.
Project description:Cadmium is a known carcinogen that can disrupt endocrine signalling. Cigarette smoking and food are the most common routes of non-occupational exposure to cadmium. Cadmium accumulates in the kidney and can be measured in urine, making urine cadmium (U-Cd) a biomarker of long-term exposure. However dietary-cadmium (D-Cd) intake estimates are often used as surrogate indicator of cadmium exposure in non-smoking subjects. It is therefore important to investigate the concordance between D-Cd estimates obtained with Food Frequency Questionnaires and U-Cd.U-Cd levels were compared with estimated dietary-cadmium (D-Cd) intake in 1764 post-menopausal women from the Danish Diet, Cancer and Health cohort. For each participant, a food frequency questionnaire, and measures of cadmium content in standard recipes were used to judge the daily intake of cadmium, normalized by daily caloric intake. Cadmium was measured by ICP-MS in spot urine sampled at baseline and normalized by urinary creatinine. Information on diet, socio-demographics and smoking were self-reported at baseline.Linear regressions between U-Cd and D-Cd alone revealed minimal but significant positive correlation in never smokers (R2 = 0.0076, ? = 1.5% increase per 1 ng Cd kcal(-1), p = 0.0085, n = 782), and negative correlation in current smokers (R2 = 0.0184, ? = 7.1% decrease per 1 ng Cd kcal(-1) change, p = 0.0006, n = 584). In the full study population, most of the variability in U-Cd was explained by smoking status (R2 = 0.2450, n = 1764). A forward selection model revealed that the strongest predictors of U-Cd were age in never smokers (? R2 = 0.04), smoking duration in former smokers (? R2 = 0.06) and pack-years in current smokers (? R2 = 0.07). Food items that contributed to U-Cd were leafy vegetables and soy-based products, but explained very little of the variance in U-Cd.Dietary-Cd intake estimated from food frequency questionnaires correlates only minimally with U-Cd biomarker, and its use as a Cd exposure indicator may be of limited utility in epidemiologic studies.
Project description:Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48??g?g-1 creatinine (geometric mean=0.94??g?g-1) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88??g?g-1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (?)=1.64, P=0.002). These associations were present among light- and never-smokers (?=2.03, P=0.002, n=2627), although not significant among never-smokers (?=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (?=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.
Project description:BACKGROUND:Low to moderate acute cadmium exposure has been associated with increased risk of chronic diseases, such as cardiovascular and kidney disease. Little is known about the association between urinary cadmium levels-an indicator of longer-term exposure-and metabolic syndrome (MetS). METHODS:We analysed data from 3982 participants aged 20-<80?years of the National Health and Nutrition Examination Survey 2001-2014. Urinary cadmium levels were measured and adjusted for creatinine using spot urine samples. Cadmium levels were evaluated in quintiles (Q). MetS was defined by National Cholesterol Education Program's Adult Treatment Panel III report criteria. Prevalence odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression accounting for complex survey design, while adjusting for potential confounders and stratifying by sex and smoking status. RESULTS:In the overall study population, there was a marginal inverse association between urinary cadmium and MetS (adj. OR for Q5 versus Q1: 0.7; 95% CI: 0.5-1.0). Sex stratified models were similar. When examining individual components of MetS, participants with higher levels of urinary cadmium had decreased odds of abdominal obesity (adj. OR for Q5 versus Q1 0.4; 95% CI: 0.3-0.6), but increased odds for low HDL (adj. OR for Q5 versus Q1 2.1; 95% CI: 1.4-3.1). Among current smokers, higher urinary cadmium was associated with increased odds of MetS, hypertension, and low HDL even after accounting for serum cotinine-a marker of smoking intensity. CONCLUSIONS:Higher levels of urinary cadmium, a marker of long term exposure, were not associated with an increased risk of MetS in the overall study population. However, higher urine cadmium was associated with altered MetS components. Current smokers were the most vulnerable group, with higher long-term cadmium exposure being associated with increased risk of MetS, low HDL, and hypertension.
Project description:Cadmium, a heavy metal dispersed in the environment as a result of industrial and agricultural applications, has been implicated in several human diseases including renal disease, cancers, and compromised bone health. In the general population, the predominant sources of cadmium exposure are tobacco and diet. Urinary cadmium (uCd) reflects long-term exposure and has been frequently used to assess cadmium exposure in epidemiological studies; estimated dietary intake of cadmium (dCd) has also been used in several studies. The validity of dCd in comparison with uCd is unclear. This study aimed to compare dCd, estimated from food frequency questionnaires, to uCd measured in spot urine samples from 1,002 participants of the Women's Health Initiative. Using linear regression, we found that dCd was not statistically significantly associated with uCd (?=0.006, P-value=0.14). When stratified by smoking status, dCd was not significantly associated with uCd both in never smokers (?=0.006, P-value=0.09) and in ever smokers (?=0.003, P-value=0.67). Our results suggest that because of the lack of association between estimated dCd and measured uCd, dietary estimation of cadmium exposure should be used with caution in epidemiologic studies.
Project description:The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (?0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.