Objectives-To validate a provocative chelation test with 2,3-dimercaptosuccinic acid (DMSA) by direct comparison with the standard ethylene diamine tetraacetic acid (EDTA) test in the same subjects; and to compare and contrast the predictors of lead excretion after DMSA with those after EDTA. A metal chelating agent given orally, DMSA may mobilise and enhance the excretion of lead from the storage sites in the body that are most directly relevant to the health effects of lead. A provocative chelation test with DMSA could thus have wide potential application in clinical care and epidemiological studies. Methods-34 male lead workers in the Republic of Korea were given a single oral dose of 10 mglkg DMSA, urine was collected over the next eight to 24 hours, and urine volume and urinary lead concentration determined at 0, 2, 4, 6, 8, and 24 hours. Either two weeks before or two weeks after the dose of DMSA 17 of these workers also received 1 g intravenous EDTA followed by an eight hour urine collection with fractionation at 0, 2, 4, 6, and 8 hours.Results-Urinary lead concentration peaked at two hours after DMSA and four hours after EDTA. Lead excretion after DMSA was less than after EDTA, and cumulative excretion after DMSA plateaued at six to eight hours. The two hour and four hour cumulative lead excretions after DMSA were highly correlated with the eight hour total (r = 0-76 and 0.95). In multiple linear regression analyses, blood lead was found to be an important predictor of EDTA-chelatable lead, whereas urinary aminolevulinic acid (ALAU) was associated with DMSAchelatable lead. Notably, lead excretion after DMSA was greatly increased if EDTA was given first. An earlier dose of EDTA also modified the relation between ALAU and DMSA-chelatable lead in that workers who received EDTA before DMSA showed a much steeper doseresponse relation between these two measures.Conclusions-The predictors of lead excretion after DMSA and EDTA are different and an earlier dose of EDTA may increase lead excretion after a subsequent dose of DMSA. The results suggest that two hour or four hour cumulative lead excretion after DMSA may provide an estimate of lead in storage sites that are most directly relevant to the health effects of lead.
We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lead exposure was assessed with job duration, blood lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and tibia lead. Renal function was assessed with blood urea nitrogen (BUN), serum creatinine, measured creatinine clearance, calculated creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG), and retinol-binding protein. Mean (+/- SD) tibia lead, blood lead, and DMSA-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0 +/- 15.0 microg/dL, and 767.8 +/- 862.1 microg/g creatinine, respectively. After adjustment, participants with the ALAD(2) allele had lower mean serum creatinine and higher calculated creatinine clearance. We observed effect modification by ALAD on associations between blood lead and/or DMSA-chelatable lead and three renal outcomes. Among those with the ALAD(1-2) genotype, higher lead measures were associated with lower BUN and serum creatinine and higher calculated creatinine clearance. Participants with the eNOS variant allele were found to have higher measured creatinine clearance and BUN. In participants with the Asp allele, longer duration working with lead was associated with higher serum creatinine and lower calculated creatinine clearance and NAG; all were significantly different from relations in those with the Glu/Glu genotype except NAG (p = 0.08). No significant differences were seen in renal outcomes by VDR genotype, nor was consistent effect modification observed. The ALAD findings could be explained by lead-induced hyperfiltration.
Objectives Environmental exposure to multiple metals is common. A number of metals cause nephrotoxicity with acute and/or chronic exposure. However, few epidemiologic studies have examined the impact of metal co-exposure on kidney function. Therefore, we evaluated associations of antimony and thallium with kidney outcomes and assessed the impact of cadmium exposure on those associations in lead workers. Methods Multiple linear regression was used to examine associations between ln-urine thallium, antimony and cadmium levels with serum creatinine- and cystatin-C-based glomerular filtration measures, and ln-urine N-acetyl-β-D-glucosaminidase (NAG). Results In 684 participants, median urine thallium and antimony were 0.39 and 0.36 μg/g creatinine, respectively. After adjustment for lead dose, urine creatinine, and kidney risk factors, higher ln-urine thallium was associated with higher serum creatinine- and cystatin-C-based estimates of glomerular filtration rate (eGFR); associations remained significant after adjustment for antimony and cadmium (regression coefficient for serum creatinine-based eGFR = 5.2 mL/min/1.73 m2; 95% confidence interval = 2.4, 8.0). Antimony associations with kidney outcomes were attenuated by thallium and cadmium adjustment; thallium and antimony associations with NAG were attenuated by cadmium. Conclusions Urine thallium levels were significantly associated with both serum creatinine- and cystatin-C-based glomerular filtration measures in a direction opposite that expected with nephrotoxicity. Given similarities to associations recently observed with cadmium, these results suggest that interpretation of urine metal values, at exposure levels currently present in the environment, may be more complex than previously appreciated. These results also support multiple metal analysis approaches to decrease the potential for inaccurate risk conclusions.
A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.
ObjectivesWe evaluated the physical and mental health problems of waged workers in Korea who had different classes of occupation.MethodsWe used data from the Korean National Health and Nutrition Examination Survey (2007–2017) to examine 22,788 workers who were waged employees and categorized these workers into 5 occupational classes.Results“Unskilled manual workers” were more likely to be older, less educated, have lower monthly income, and work fewer hours per week. Among men and relative to “managers and professionals” (reference group), “skilled manual workers” were more likely to have physician-diagnosed osteoarthritis, “clerks” were less likely to report suicidal ideation, and “unskilled manual workers” were more likely to report suicidal ideation. Among women and relative to “managers and professionals” (reference group), “service and sales workers” and “unskilled manual workers” were more likely to report physician-diagnosed osteoarthritis, depressive feelings, and suicidal ideation. However, hypertension, hyperlipidemia, diabetes, and cardiovascular diseases did not differ among the occupational classes for men and women.ConclusionWe identified differences between men and women and among those in different occupational classes regarding employment status, physical health, and mental health. “Unskilled manual workers” of both genders were more likely to be older, less educated, have less monthly income, work fewer hours per week, and have suicidal ideation. Female “service and sales workers” were more likely to have osteoarthritis, depressive feelings, and suicidal ideation.
The association between metabolic syndrome and eating patterns remains unclear. We hypothesized that Korean Healthy Eating Index (KHEI) scores were related to metabolic syndrome (MetS) risk in adults in a gender-dependent manner. We aimed to examine the hypothesis using the Korea National Health and Nutrition Examination Survey-VI (2013–2017) data with a complex sample survey design. Adjusted means and 95% confidence intervals of KHEI scores and nutrient intake estimated by the 24-h recall were calculated according to MetS status after adjusting for age, residence area, region, education, obesity, income, drinking status, smoking status, marriage, and exercise. Adjusted odds ratios for MetS were measured according to KHEI quartiles using logistic regression analysis while controlling for covariates. MetS incidence was significantly higher in females than in males. Those who were older, less educated, earning less income, more obese, living in rural areas, drinking severely, non-exercising, and married had higher MetS incidence than those with the opposite state. Total KHEI scores of all components KHEI scores were lower for those with MetS (MetS group) than those without MetS (Non-MetS group) in both genders. For KHEI components, having breakfast and milk and fat intake had lower scores for the MetS group than for the Non-MetS group in women, whereas fruits and milk and milk product intake had lower scores for the MetS group in men. Nutrient intake influenced the MetS risk in females more than in males. Fat, calcium, and vitamin C intakes from 24-h recall were lower in the MetS group than in the Non-MetS group in women. KHEI scores had an inverse association with MetS risk by 0.98-fold in both genders after adjusting for covariates. In conclusion, a healthy diet that includes adequate calcium and vitamin C is associated with a lower the risk of MetS in both men and women.
In this paper, we hypothesized that the gap between estimated cardiovascular age (eCV-age) and chronological age had a gender-wise correlation with the Korean Healthy Eating Index (KHEI). We tested the hypothesis in adults aged 20–64 years old using the KNHANES 2013–2017 data. eCV-age was estimated based on the designated risk factors of cardiovascular disease (CVD) and age-gap was calculated by subtracting the eCV-age from the chronological age in 12,317 adults. Adjusted odds ratios for the age-gap were measured according to KHEI, while controlling for covariates to influence risk factors of CVD, using logistic regression analysis with the complex sample survey design. Age-gaps were divided into four groups: >4 (High), 0–4 (Moderate), −4–0 (Mild), and <−4 years (Low). The higher the age-gap, the lower the cardiovascular risk. Persons included in the following categories belonged to the high and moderate age-gap groups: young (<40 years), women, urban living, better than high school education, higher income, lean, mild drinking, and exercising regularly. KHEI scores were overall higher in women than men (p < 0.01). Having breakfast and saturated fat intake were primary factors that influenced the age-gap for men, whereas fresh fruit intake and carbohydrate intake influenced the age-gap in women. The KHEI scores positively correlated with nutrient intake, especially fiber and vitamin C intake in women (p < 0.05). Participants with high KHEI scores increased their chances of belonging to the high age-gap group by 2.16 times for men and 2.10 for women after adjusting for covariates of sex, age, and residence. However, after adding the covariates of education, income, marriage, and obesity, in conjunction with smoking, alcohol, and regular exercise, this reduced to 1.34 times in women. In conclusion, both genders had a positive correlation between age-gap and overall KHEI scores.
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