Yasushi Suwazono

A Longitudinal Study on the Effect of Shift Work on Weight Gain in Male Japanese Workers

Objective: This study compared the effect of alternating shift work and day work on weight gain in Japanese male workers.

Creatinine versus specific gravity-adjusted urinary cadmium concentrations.

Abstract The aim was to assess how urinary creatinine is affected by age, gender, body size and meat intake, and to determine to what extent such factors might affect the creatinine adjustment of urinary cadmium. The study was based on three Swedish studies: (1) 67 non-smoking women aged 20–50 years (24-h urine samples); (2) 289 men and 434 women aged 16–81 years (spot urine samples); and (3) 98 men and 105 women aged 19–72 years (spot urine samples). The effects of age, body surface area (as an indicator of muscle mass), and meat intake on urinary creatinine and cadmium were analysed using multiple regression analyses. Gender- and age-related variations in urinary creatinine and cadmium adjusted for creatinine or specific gravity were compared by ANOVA or ANCOVA. In the multiple regression analyses, body surface area, gender, age and meat intake were the major determinants of urinary creatinine. Urinary cadmium adjusted for creatinine and specific gravity were also dependent on body size, gender and age. Urinary cadmium adjusted for creatinine was 15–92% higher in women or older individuals than in men or younger individuals. Women or older individuals had –3 to 79% higher urinary cadmium adjusted for specific gravity than men or younger individuals had, and such a difference between gender or age group was less obvious in specific gravity adjustment than in creatinine adjustment. Thus, urinary cadmium adjusted for creatinine is more affected by age, gender, body size and meat intake than is specific gravity adjustment. When comparing individuals or populations with large differences in muscle mass or meat intake, such effects can be especially important. In such studies, specific gravity adjustment seems to be more appropriate.

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.

Shift Work Is a Risk Factor for Increased Blood Pressure in Japanese Men. A 14-Year Historical Cohort Study

To clarify the effect of shift work on blood pressure in Japanese men, a 14-year historical cohort study was conducted in day workers (n=3963) and alternating shift workers (n=2748) who received annual health checkups between 1991 and 2005 in a Japanese steel company. The end points were a ≥10%, ≥15%, ≥20%, ≥25%, or ≥30% increase in systolic blood pressure or diastolic blood pressure from baseline during the period of observation. The association between shift work and an increase in blood pressure was investigated adjusting for age, body mass index, hemoglobin A1c, total serum cholesterol, creatinine, aspartate aminotransferase, &ggr;-glutamyl transpeptidase, uric acid, drinking habit, smoking habit, and habitual exercise by multivariate pooled logistic regression analyses. Shift work was significantly associated with the various end points. The odds ratios (and 95% CIs) were as follows: ≥10%, 1.15 (1.07 to 1.23); ≥15%, 1.21 (1.12 to 1.31); ≥20%, 1.15 (1.04 to 1.28); ≥25%, 1.20 (1.06 to 1.37); and ≥30%, 1.23 (1.03 to 1.47) for systolic blood pressure and ≥10%, 1.19 (1.11 to 1.28); ≥15%, 1.22 (1.13 to 1.33); ≥20%, 1.24 (1.13 to 1.37); and ≥25%, 1.16 (1.03 to 1.30) for diastolic blood pressure. Our study in male Japanese workers revealed that alternating shift work was a significant independent risk factor for an increase in blood pressure. Moreover, the effect of shift work on blood pressure was more pronounced than other well-established factors, such as age and body mass index.

[Itai-itai disease].

Itai-Itai disease was first reported as a unique disease without any known cause in an academic conference in October 1955. Most of the patients affected by this new peculiar disease were middle-aged or older women who complained of severe pain and developed bone fractures with minimal force. In May 1968, the Ministry of Health and Welfare announced that chronic cadmium poisoning first caused renal impairment and then osteomalacia, and defined this entity as Itai-Itai (Ouch-Ouch) disease. The correlation coefficient between the prevalence of Itai-Itai disease patients according to hamlet and Cd concentrations in rice was 0.51. The correlation coefficient between the prevalence of Itai-Itai disease patients and urinary protein+urinary glucose positive rates was 0.74. Considering these close interrelationships between the development of Itai-Itai disease, Cd concentrations in rice, prevalence of renal injury, clinical course of Itai-Itai disease, and high prevalence of persons with renal impairment in these districts, it is reasonable to conclude that ingestion of Cd in rice induces renal injury, with Itai-Itai disease developing among those most severely affected. Several thousands of inhabitants manifest renal tubular dysfunction in cadmium-polluted districts. As of July 2009, 195 persons were officially designated as Itai-Itai disease patients and 336 residents were determined as being persons requiring further observation (suspected patients) in the cadmium-polluted Jinzu River basin.

Benchmark Dose for Cadmium-Induced Renal Effects in Humans

Objectives Our goal in this study was to explore the use of a hybrid approach to calculate benchmark doses (BMDs) and their 95% lower confidence bounds (BMDLs) for renal effects of cadmium in a population with low environmental exposure. Methods Morning urine and blood samples were collected from 820 Swedish women 53–64 years of age. We measured urinary cadmium (U-Cd) and tubular effect markers [N-acetyl- β-D-glucosaminidase (NAG) and human complex-forming protein (protein HC)] in 790 women and estimated glomerular filtration rate (GFR; based on serum cystatin C) in 700 women. Age, body mass index, use of nonsteroidal anti-inflammatory drugs, and blood lead levels were used as covariates for estimated GFR. BMDs/BMDLs corresponding to an additional risk (benchmark response) of 5 or 10% were calculated (the background risk at zero exposure was set to 5%). The results were compared with the estimated critical concentrations obtained by applying logistic models used in previous studies on the present data. Results For both NAG and protein HC, the BMDs (BMDLs) of U-Cd were 0.5–1.1 (0.4–0.8) μg/L (adjusted for specific gravity of 1.015 g/mL) and 0.6–1.1 (0.5–0.8) μg/g creatinine. For estimated GFR, the BMDs (BMDLs) were 0.8–1.3 (0.5–0.9) μg/L adjusted for specific gravity and 1.1–1.8 (0.7–1.2) μg/g creatinine. Conclusion The obtained benchmark doses of U-Cd were lower than the critical concentrations previously reported. The critical dose level for glomerular effects was only slightly higher than that for tubular effects. We suggest that the hybrid approach is more appropriate for estimation of the critical U-Cd concentration, because the choice of cutoff values in logistic models largely influenced the obtained critical U-Cd.

The relationship between shift work and the onset of hypertension in male Japanese workers.

Learning ObjectivesRecall the prevalence of hypertension in this study of Japanese steel company employees during nearly 5 years of follow-up.Describe the observed differences between day workers and shift workers in blood pressure, body size, and life style.Specify the risk of hypertension in shift workers compared to day workers, and the life style and clinical factors that were significantly associated with its occurrence. We assessed the effect of shift work on the onset of hypertension. The design of this study was that of a cohort study from 1991–2001. In sum, 5338 workers comprised this cohort. The event was the onset of hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or medication). Pooled logistic regression analysis was performed, including job schedule type, age, body mass index, lifestyle, and the results of blood chemistries as covariates. The odds ratio of the onset of hypertension in shift workers for daytime workers was 1.10 and significant. Our study revealed that shift work independently affected the onset of hypertension, and suggested that shift work is a risk factor for the onset of hypertension.

Long-Term Cadmium Exposure and the Association With Bone Mineral Density and Fractures in a Population-Based Study Among Women

All people are exposed to cadmium (Cd) via food; smokers are additionally exposed. High Cd exposure is associated with severe bone damage, but the public health impact in relation to osteoporosis and fractures at low environmental exposure remains to be clarified. Within the population‐based Swedish Mammography Cohort, we assessed urinary Cd [U‐Cd, µg/g of creatinine (cr)] as a marker of lifetime exposure and bone mineral density (BMD) by dual‐energy X‐ray absorptiometry (DXA) among 2688 women. Register‐based information on fractures was retrieved from 1997 to 2009. Associations were evaluated by multivariable regression analyses. In linear regression, U‐Cd was inversely associated with BMD at the total body (p < .001), femoral neck (p = .025), total hip (p = .004), lumbar spine (p = .088), and volumetric femoral neck (p = .013). In comparison with women with U‐Cd < 0.50 µg/g of cr, those with U‐Cd ≥ 0.75 µg/g of cr had odds ratios (ORs) of 2.45 [95% confidence interval (CI) 1.51–3.97] and 1.97 (95% CI 1.24–3.14) for osteoporosis at the femoral neck and lumbar spine, respectively. Among never‐smokers, the corresponding ORs were 3.47 (95% CI 1.46–8.23) and 3.26 (95% CI 1.44–7.38). For any first fracture (n = 395), the OR was 1.16 (95% CI 0.89–1.50) comparing U‐Cd ≥ 0.50 µg/g of cr with lower levels. Among never‐smokers, the ORs (95% CIs) were 2.03 (1.33–3.09) for any first fracture, 2.06 (1.28–3.32) for first osteoporotic fracture, 2.18 (1.20–3.94) for first distal forearm fracture, and 1.89 (1.25–2.85) for multiple incident fractures. U‐Cd at low environmental exposure from food in a general population of women showed modest but significant association with both BMD and fractures, especially in never‐smokers, indicating a larger concern than previously known.

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.

SHIFTWORK AND IMPAIRED GLUCOSE METABOLISM: A 14-YEAR COHORT STUDY ON 7104 MALE WORKERS

The aim of this study was to assess the effect of shiftwork on hemoglobin A1c (HbA1c) level, as an index of glucose metabolism. A 14 yr prospective cohort study was conducted on day (n = 4219) and alternating shiftworkers (n = 2885) who received annual health checkups between 1991 and 2005 at a Japanese steel company. The endpoints were either a 10%, 15%, 20%, 25%, or 30% increase in HbA1c during the period of observation, compared to HbA1c at entry to the study. The association between the type of job schedule and increase in HbA1c was investigated after adjusting for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, drinking habit, smoking habit, and habitual exercise using multivariate pooled logistic regression analyses. Shiftwork was significantly associated with the various HbA1c endpoints (≥10% HbA1c increase, odds ratio 1.35 [95% confidence interval 1.26–1.44]; ≥15% HbA1c increase, odds ratio 1.29 [95% confidence interval, 1.19–1.40]; ≥20% HbA1c increase, odds ratio 1.23 [95% confidence interval 1.11–1.37]; and ≥25% HbA1c increase, odds ratio 1.19 [95% confidence interval 1.03–1.36]). Age, body mass index, alanine aminotransferase, and γ-glutamyl transpeptidase were associated positively with all five HbA1c endpoints. Uric acid was associated negatively with all five HbA1c endpoints. Our study on male Japanese workers revealed alternating shiftwork (in addition to other established factors, such as age and body mass index) was a consistent risk factor for impaired glucose metabolism.