Mirei Uetani

Long-term Longitudinal Study on the Relationship Between Alternating Shift Work and the Onset of Diabetes Mellitus in Male Japanese Workers

Objective: This study investigated the effect of alternating shift work (ASW) on the onset of diabetes mellitus in Japanese workers compared with onset in day-shift work (DSW). Methods: A longitudinal study was carried out on a DSW group (n = 3203) and ASW group (n = 2426) of a steel company who received their annual health checkups over a 10-year period between 1991 and 2001. The association between job schedule type and onset of diabetes mellitus (glycated hemoglobin A1c ≥6.0% or medication) was investigated by multivariate pooled logistic regression analyses. Results: The odds ratio (95% confidence interval) for the development of diabetes mellitus in the ASW group compared with the DSW group was 1.35 (1.05–1.75). Conclusions: Our study revealed that the ASW is an independent risk factor for the onset of diabetes mellitus.

A longitudinal study on the relationship between shift work and the progression of hypertension in male Japanese workers.

Objective In this 1991–2001 cohort study of 6495 male workers in a Japanese steel company, we investigated whether shift work affects progression from mild hypertension to severe hypertension. Design A prospective cohort study. Participants Participants had mild hypertension at entry into the study with systolic blood pressure of 140–159 mmHg or diastolic blood pressure of 90–99 mmHg or both before treatment. In summary, 2911–2941 workers were included for each endpoint. Pooled logistic regression analysis was performed to adjust for the effect of contributing factors and annual variations. Main outcome Either severe hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg), severe systolic hypertension (systolic blood pressure ≥ 160 mmHg) or severe diastolic hypertension (diastolic blood pressure ≥ 100 mmHg) was defined as a different endpoint of observation. Results Job schedule was significantly associated with progression from mild hypertension to severe hypertension and severe diastolic hypertension. The odds ratios of shift workers compared with regular day workers were 1.23 (95% confidence interval: 1.05–1.44) and 1.28 (95% confidence interval: 1.07–1.52) for severe hypertension and severe diastolic hypertension, respectively. Age, body mass index, creatinine, γ-glutamyl transpeptidase, and glycosylated hemoglobin A1c were also significantly associated with severe hypertension, severe systolic hypertension and severe diastolic hypertension. Conclusion Our study revealed that shift work is a significant and independent risk factor for the progression of hypertension.

Three-shift system increases job-related stress in Japanese workers.

Three‐Shift System Increases Job‐Related Stress in Japanese Workers: Hideto Harada, et al. Department of Occupational and Environmental Medicine, Graduate School of Medicine, Chiba University—We assessed the relationship between shift work and job stress. The target subjects were 4,962 male workers (3,078 day workers and 1,884 shift workers) aged 18 to 60 yr who work in a Japanese steel company. We used the “Brief Job Stress Questionnaire”, which was developed by a research group organized by the Japanese Ministry of Labour. We evaluated the effect of shift work on job stress using logistic regression analysis including age, lifestyle factors, work conditions, marital status, and living arrangements in the model. Job schedule type was significantly associated with job control, with an odds ratio of 2.22 for shift workers compared to day workers. The logistic regression analysis revealed that the odd ratios for having one or more stressor items in an unfavorable condition were significantly higher for shift workers compared to day workers. Increase in the amount of overtime and decrease in the number of holidays led to a significant deterioration in job stress. Our study reveals that the 3‐shift system of employment increases work‐related stress, and that job control is low among shift workers. To reduce job stress in this occupational population, a reduction in the amount of overtime and an increase in the number of holidays seem to be useful interventions.

Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan

There are more than 50 cadmium (Cd) polluted areas in Japan. The severest general environmental Cd polluted area in Japan was the Jinzu River basin in Toyama Prefecture where Itai-itai disease had been endemic. The present study aimed to compare organ Cd concentrations of inhabitants who had been exposed to different levels of environmental Cd and to clarify the health effects of the environmental Cd exposure in Japan. Since 1960 we have measured tissue Cd concentrations of inhabitants with a history of living in a different Cd polluted areas. Study population living in Cd polluted areas were 36 (1 male, 35 females) patients with Itai-itai disease, 20 (7 males, 13 females) subjects suspected of having Itai-itai disease, 8 (2 males, 6 females) inhabitants in Cd polluted areas other than the Jinzu River basin. Subjects who had lived in Cd non-polluted area were 72 inhabitants. Cd concentrations in liver, pancreas and thyroid of those living in Cd polluted areas were as high as those of patients with Itai-itai disease, and their Cd concentrations in renal cortex were as low as those of patients with Itai-itai disease. The present study demonstrated that tissue Cd concentrations of some inhabitants in Cd polluted areas other than Jinzu River basin are equal to those of the patients with Itai-itai disease and that patients with Itai-itai disease were present even in these areas.

Recent applications of benchmark dose method for estimation of reference cadmium exposure for renal effects in man

The initial sign of cadmium (Cd)-induced renal effects is tubular damage, followed by glomerular damage. For the prevention of Cd-induced renal effects, it is essential to establish the reference exposure below which the risk of adverse health effects is low. In earlier Japanese studies, the estimated reference exposure of creatinine (cre)-adjusted urinary cadmium for renal tubular effect ranged from 1.6 to 4.0 microg/g cre in men and 2.3 to 4.6 microg/g cre in women. The benchmark dose (BMD) is defined as the exposure that corresponds to a certain response change from the background. The lower 95% confidence limit of the BMD (BMDL) can be used in risk assessment as a replacement for the no observed adverse effect level. This is a review of all relevant BMDL of Cd exposure for renal effects estimated so far. Based on studies in Japan, the best estimate is considered to be 1.5-3.2 microg/g cre for urinary Cd, 0.09-0.13 mg/kg for rice Cd concentration, and 0.9-1.4 g Cd for lifetime Cd intake. These BMDLs for renal effects were generally lower than the reference exposure expected from earlier studies, indicating the importance of further discussion regarding comprehensive measures to decrease the Cd exposure in the general population.

Reassessment of the threshold of urinary cadmium by using hybrid approach in a cadmium non-polluted area in Japan

BACKGROUND AND OBJECTIVES We applied an updated hybrid approach to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for cadmium-induced renal effects as the threshold of urinary cadmium in humans. Using this method, the BMD and BMDL were estimated based on continuous exposure and continuous effect marker, thereby avoiding categorization of subjects, an inevitable outcome of previously used approaches. METHODS The target subjects were 547 men and 723 women, aged 50 years or older, who lived in a cadmium non-polluted area of Japan. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and urinary protein, β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG) as renal effect markers. BMD and BMDL corresponding to an additional risk (BMR) of 5%, were calculated with the background risk at zero exposure set at 5%. RESULTS AND CONCLUSIONS The BMDL of U-Cd for renal effect markers were 2.1 (urinary protein), 2.6 (β2-MG) and 4.1 (NAG) μg/g creatinine in men and 1.5 (urinary protein), 1.4 (β2-MG) and 3.1 (NAG) μg/g creatinine in women. The BMDLs in the present study may contribute to further discussion on health risk assessment of cadmium exposure, when compared to BMDLs obtained by previously reported methods.

Estimation of benchmark doses for urinary cadmium based on β2-microglobulin excretion in cadmium-polluted regions of the Kakehashi River basin, Japan

Abstract A benchmark dose low (BMDL) is used as a replacement for the no observed adverse effect level. The threshold levels of urinary cadmium (Cd) as BMDL were estimated using data from the Kakehashi River basin. The target population (≥50 years) comprised 3178 and 294 participants inhabiting Cd-polluted and non-polluted areas, respectively. Cut-off values for β2-MG-uria were defined as the 84 and 95% upper limit values calculated from control subjects, and 1000 µg/l or µg/g cr of β2-MG. Using these cut-off values, the BMDL at which the excess risk is 0.05 was determined to be 2.9 – 4.0 µg/g cr (males) and 1.5 – 3.6 µg/g cr (females). The present study demonstrated that a BMD approach is useful to estimate the threshold level of urinary Cd in Cd-exposed subjects and people living in general environment without any known Cd-pollution since a BMD approach does not need abnormality rates of urinary findings in the controls.

ESTIMATION OF THE BENCHMARK DURATION OF SHIFTWORK ASSOCIATED WITH WEIGHT GAIN IN MALE JAPANESE WORKERS

The authors estimated the benchmark durations (BMDs) and their 95% lower confidence limit (BMDL) for the reference duration of shiftwork for weight gain. A 14-yr prospective cohort study was conducted in male workers at a Japanese steel company (n = 7254) who had received annual health check-ups between 1991 and 2005. The endpoints in the study were either a 5%, 7.5%, or 10% increase in body mass index (BMI) during the period of observation, compared to the BMI at entry. The association between the duration of shiftwork and weight gain was investigated using multivariate pooled logistic regression analyses with stepwise selection of covariates, including age, BMI measured during the study, drinking and smoking habits, and habitual exercise. The BMDL/BMD for shiftwork in subjects aged in their 40s or ≥50 yrs was estimated using benchmark responses (BMRs) of 5% or 10% and parameters for the duration of shiftwork and other covariates. For workers aged in their 40s, the BMDL/BMD for shiftwork with a BMR of 5% was 18.6/23.0 yrs (≥7.5%) and 16.9/19.4 yrs (≥10%). For workers aged ≥50 yrs, the BMDL/BMD with a BMR of 5% was 22.9/28.2 yrs (≥7.5%) and 20.6/23.6 yrs (≥10%). The reference duration of shiftwork that associated with weight gain was shown to be at least 17 yrs in middle-aged workers. Special attention should be paid to prevent weight gain at an earlier stage and not when this increase in weight has become apparent. (Author correspondence: suwa@faculty.chiba-u.jp)

Excretion of urinary cadmium, copper, and zinc in cadmium-exposed and nonexposed subjects, with special reference to urinary excretion of β2-microglobulin and metallothioneinand metallothionein

The objectives of this study were to examine the association between urinary excretion of cadmium (U-Cd) copper (U-Cu), and zinc (U-Zn) and the severity of two different indicators of renal toxicity (urinary excretion of β2-microglobulin [U-β2-MG] and metallothionein [U-MT]) in Cd-exposed subjects compared to controls, and to assess the physiologic mechanisms by which the exposure to environmental Cd affects U-Cd, U-Cu, and U-Zn. The target population included 3508 Cd-exposed and 294 nonexposed participants who received a health survey conducted among the population of the Kakehashi River basin. Increases of U-Cd, U-β2-MG, and U-MT in the Cd-exposed population were observed relative to excretion of these substances in controls Regression analysis using a general linear model revealed that the correlations between U-Cd or U-Cu, and U-β2-MG and between U-Cd, U-Cu or U-Zn, and U-MT were statistically significant in both sexes, but the correlation between U-Zn and U-β2-MG excretion was significant only in men. These results suggest U-Cd and U-Cu is affected by dysfunction in renal tubular absorption (indicated by U-β2-MG), whereas not only U-Cd and U-Cu but also U-Zn appear to be a function of renal cellular desquamation (indicated by U-MT).

Association between exposure to cadmium and blood pressure in Japanese peoples

Abstract The authors studied the effects of environmental cadmium exposure on blood pressure (BP). Subjects 1,140 men and 1,713 women, aged ≥ 50 yr lived in three areas of Japan considered “unpolluted” by cadmium. Multiple logistic regression analysis was used to evaluate relationships between hypertension/nonhypertension and cadmium concentrations in blood (B-Cd) or urine (U-Cd). Age, body mass index, drinking and smoking habits, and blood and urine chemistry data were incorporated into the model. Odds ratios for hypertension were significantly less than 1 in either gender when U-Cd was the indicator of cadmium exposure and hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg. The results suggest a significant negative association between cadmium exposure and BP in inhabitants in Japan.