能川 和浩

OBJECTIVES: The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all-cause mortality after compulsory retirement in Japan. METHODS: The 2026 participants (1299 males and 727 females) had retired from a metal-products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all-cause mortality was assessed by Cox proportional hazards regression analysis. RESULTS: During the study, 71 deaths were reported. The age- and sex-adjusted hazard ratio (HR [95% confidence interval]) for all-cause mortality was higher for males (HR, 3.41 [1.73-6.69]) compared with females, participants with a low body mass index (<18.5 kg/m2 ; HR 3.84 [1.91-7.73]) compared with normal body weight, smokers (HR, 2.63 [1.51-4.58]) compared with nonsmokers, and those with three or more of four metabolic abnormalities (obesity, high blood pressure, dyslipidemia, and glucose intolerance) (HR 2.29 [1.04-5.02]) compared with no metabolic abnormalities. The associations were unaffected by adjustment for these factors. CONCLUSION: Maintenance of an appropriate body weight, smoking cessation, and elimination of metabolic syndrome are required for older workers to prevent early death after retirement.

Background: Exposure to cadmium (Cd) via food is supposed to affect life prognosis of inhabitants of Cd-polluted area in Japan. However, there have been few reports demonstrating a significant relationship between the amount of Cd intake and mortality. We aimed to investigate the relationship between mortality and individual lifetime Cd intake (LCd) in inhabitants of the polluted Jinzu River basin, Toyama, Japan. Methods: We conducted a 26-year follow-up survey in 2407 inhabitants (1208 men and 1199 women) who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The calculation of LCd in each inhabitant was based on the formula of Nogawa (Nogawa et al., 1989): (mean Cd concentration in rice of the present hamlet × 333.5 g/day + 34 μg/day) × 365 days/year × number of years of residence in the present hamlet + 50 μg/day × 365 days/year × number of years living in Cd non-polluted regions. In this formula, 333.5 g/day is the 1970 average daily intake of rice in this area, 34 µg/day is the Cd intake from foods other than rice in this area, and 50 μg/day is the average intake of Cd in non-polluted areas in Japan. Mortality risk ratios of LCd for all and specific causes were estimated after adjustments for age at baseline, smoking status, and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. Results: The mortality risk ratios of LCd (+ 1 g) for all causes in women were significantly dose-dependently increased (risk ratio: 1.08). Relative risk of LCd for kidney and urinal tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly higher in women. Conclusions: The present study documents that individual LCd dose-dependently decreased life prognosis over long-term observation in women. LCd was significantly related to the increased mortality for renal disease and toxic effect of Cd in women. The result provides clear evidence that life prognosis was adversely affected by Cd-exposure, especially in women.

The aim of this study was to investigate the relationship between mortality and rice cadmium (Cd) concentration in inhabitants of a polluted area in Japan. The target subjects were inhabitants of the Jinzu River basin who participated in health examinations for screening of renal dysfunction from 1979 to 1984. The mean rice Cd concentration in each hamlet was used as an index of the Cd exposure. We conducted a 26 year follow-up survey in 3281 inhabitants (1544 men and 1737 women) whose data regarding the rice Cd concentration were available. Mortality risk ratios for all and specific causes were estimated after adjustments for age at baseline, smoking status and history of hypertension using a Cox hazard model or Fine and Gray competing risks regression model. The mortality risk ratios of rice Cd concentration (+0.1 ppm) for all causes in women were significantly increased (risk ratio: 1.04). Furthermore, the relative risks of rice Cd concentration for kidney and urinary tract disease, renal diseases, renal failure and toxic effects of cadmium were significantly increased in both sexes. These findings indicated that increased rice Cd concentration decreased the prognosis for life over a long-term observation in women. This result provides important information for determining the worldwide standard for allowable rice Cd concentration.

After 26 years, we followed up 7348 participants in a 1979-1984 health screening survey in the Jinzu River basin, the heaviest cadmium-polluted area in Japan. We assessed the associations of cadmium exposure levels and mortality from cancer and renal damage, indicated by records of proteinuria and glucosuria in the original survey. Mortality risks (hazard ratios) were analyzed using the Cox proportional hazards model, stratified by sex, after adjusting for age, smoking status, and hypertension, as indicated in the original survey records. In men, the adjusted hazard ratio for mortality from lung cancer was significantly lower in individuals residing in an area of historically high cadmium exposure and in subjects with a historical record of proteinuria, glucosuria, and glucoproteinuria. The risk of mortality from prostate cancer was borderline higher in cadmium-exposed men. In women, historical cadmium exposure was not associated with an increased risk of mortality from malignant neoplasms, but the adjusted hazard ratios for death from total malignant neoplasms or from renal and uterine cancers were significantly higher in exposed subjects with a historical record of proteinuria, glucosuria, and glucoproteinuria. These findings suggest that women residing in cadmium-polluted areas who exhibit markers of renal damage may be at risk of dying of cancer.

The absorption of cadmium(Cd) may lead to Cd-related diseases such as renal tubular dysfunction and bone disease, and it is known to take around 10-30 years to reduce Cd concentrations to half their original levels. Urinary beta(2)-microglobulin (beta(2)-MG), N-acetyl-beta-D-glucosaminidase (NAG), protein, glucose and albumin were used as indicators of renal dysfunction caused by Cd exposure. Our previous study found that urinary Cd concentrations had increased recently and that age was more strongly associated with urinary beta(2)-MG concentration than recent Cd body burden. Therefore, the purpose of the present study was to investigate the effect of aging on Cd concentrations and renal dysfunction. The Cd, beta(2)-MG, NAG, protein, glucose and albumin concentrations in the urine of 40 Japanese subjects (20 females and 20 males) environmentally exposed to Cd were collected. They lived in the Kakehashi River basin and were divided into three age categories: 50-69, 70-79 and 80-99 years. Significant differences in urinary Cd and beta(2)-MG concentrations were found among age groups, with urinary Cd levels tending to increase with age in both sexes. No significant correlations were found between urinary Cd and any indicators of renal dysfunction. The correlation between age, Cd and indicators of renal dysfunction was observed more clearly in females than in males. Age is more strongly correlated with indicators of renal dysfunction than Cd body burden. Copyright (C) 2017 JohnWiley & Sons, Ltd.

The aim of this study was to estimate the benchmark dose (BMD) as the threshold limit level of the cadmium (Cd) concentration in rice for itai-itai disease and/or suspected disease; it was based on the data that previously evaluated the association for such diseases with the Cd concentration in rice by using a logistic regression model. From 1971 to 1976, a total of 2446 rice samples were analyzed across the 88 hamlets in the Jinzu river basin. The mean Cd concentration in rice in each hamlet was used as the index of external Cd exposure of the entire population of the hamlet. We employed the incidence of itai-itai disease and/or suspected disease obtained from the available 55 hamlets. As the threshold, the lower limit of the BMD (BMDL) of the Cd concentration in rice for itai-itai disease and/or suspected disease was estimated using a logistic model, setting the benchmark response at 1% or 2%. The estimated BMDLs of the Cd concentration in rice for itai-itai disease and/or suspected disease were 0.62-0.76 and 0.27-0.56mg kg(-1) in men and women, respectively. The lowest BMDL was 0.27mg kg(-1) in women. In the present study, the threshold limit level of the Cd concentration in rice for itai-itai disease, which is the most severe form of chronic Cd poisoning, was estimated for the first time. This result provides important information about the worldwide standard for the Cd concentration in rice. Copyright (c) 2017 John Wiley & Sons, Ltd. The aim of this study was to estimate the lower limit of the benchmark dose (BMDL) as the threshold limit level of the Cd concentration in rice for itai-itai disease and/or suspected disease based upon a logistic regression model. The estimated BMDLs of the Cd concentration in rice for itai-itai disease and/or suspected disease were 0.62-0.76 and 0.27-0.56mg kg(-1) in men and women, respectively. This result provides important information about the worldwide standard for the Cd concentration in rice.

Objective To clarify the causes of deaths among patients with Itai-itai disease and severe cadmium (Cd) poisoning. Design Nested case-control analysis of a population-based cohort study. Setting Database of patients with Itai-itai disease and residents of Cd-polluted areas, maintained by the Ministry of Environment, Japan. Participants Subjects included 142 women with Itai-itai disease, 111 women with Cd-induced renal tubular dysfunction and 253 controls matched for sex, age and occupation. All subjects participated in a health impact survey between 1979 and 1984 and were followed until 30 November 2005. Main outcomes and measures Adjusted HRs with 95% CIs for cause of death in women with Itai-itai disease and screened female cases with tubular dysfunction were compared with matched pair controls, using Cox's proportional hazard model. Vital statistics data were used to determine cause of death. Direct causes of death from autopsy records were used in 29 patients who died from Cd poisoning. Results The most common cause of death among patients with Itai-itai disease was pneumonia, with a significantly increased adjusted HR of 4.54 (95% CI 2.65 to 7.76). Renal diseases were the most common cause of death in renal tubular dysfunction cases, with an increased HR of 12.0 (95% CI 3.92 to 36.8). The adjusted HR for renal diseases was also significantly increased in patients with Itai-itai disease (19.49 (95% CI 6.43 to 59.09)), with a greater impact on mortality of patients with Itai-itai disease than screened cases. The HR for gastrointestinal (GI) diseases was significantly increased (13.79 (95% CI 3.87 to 49.10)) in patients, especially in the first 10 years (37.1 (4.81 to 286.0)). Conclusions Among patients with Itai-itai disease, pneumonia and GI diseases contributed to increased mortality risk. Renal disease is also a significant mortality risk in patients with Itai-itai disease and women with renal tubular dysfunction.

The aim of this study is to estimate the reference level of lifetime cadmium intake (LCd) as the benchmark doses (BMDs) and their 95% lower confidence limits (BMDLs) for various renal effects by applying a hybrid approach. The participants comprised 3,013 (1,362 men and 1,651 women) and 278 (129 men and 149 women) inhabitants of the Cd-polluted and nonpolluted areas, respectively, in the environmentally exposed Kakehashi River basin. Glucose, protein, aminonitrogen, metallothionein, and (2)-microglobulin in urine were measured as indicators of renal dysfunction. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at zero exposure set at 5%. The obtained BMDLs of LCd were 3.7 g (glucose), 3.2 g (protein), 3.7 g (aminonitrogen), 1.7 g (metallothionein), and 1.8 g ((2)-microglobulin) in men and 2.9 g (glucose), 2.5 g (protein), 2.0 g (aminonitrogen), 1.6 g (metallothionein), and 1.3 g ((2)-microglobulin) in women. The lowest BMDL was 1.7 g (metallothionein) and 1.3 g ((2)-microglobulin) in men and women, respectively. The lowest BMDL of LCd (1.3 g) was somewhat lower than the representative threshold LCd (2.0 g) calculated in the previous studies. The obtained BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure.

Background: To estimate the benchmark dose (BMD) and their 95% lower confidence limits (BMDL) of alcohol consumption as the reference level for the development of hyperuricemia based on the dose -response relationship. Methods: An 8-year prospective cohort study was conducted in 8097 male workers at a Japanese steel company who received annual health check-ups between 2002 and 2009. The endpoints for development of hyperuricemia were defined as a uric acid &gt;= 7 mg/dL or taking any anti-hyperuricemic medication. The dose-response relationship of alcohol consumption was investigated using multivariate pooled logistic regression analyses adjusted for other potential covariates. We estimated the BMD and BMDL of alcohol consumption for the development of hyperuricemia, using the parameters obtained by pooled logistic regression with a benchmark response (BMR) of 5% or 10%. Results: Mean observed years per person was 3.86 years. The incidence rate per 1000 person-years was 61.1. The odds ratio calculated for the development of hyperuricemia was 1.29 [95% confidence interval, (1.22-1.36)] with an increase in alcohol consumption per 1 gou/day (1 gou/day = alcohol 22 g/day). The estimated BMDL/BMD with a BMR of 5% was 2.5/2.8 gou/day (54.5/61.8 g/day) and with a BMR of 10% was 4.0/4.6 gou/day (88.9/100.9 g/day). Conclusions: The present study showed that alcohol consumption of 2.5 gou/day (=ethanol 55 g/day) caused a distinct increase in the risk of hyperuricemia. Valuable information for preventing alcohol induced hyperuricemia was obtained by a long-term follow-up study of a large cohort. (C) 2016 Elsevier Inc. All rights reserved.

Half-life of urinary cadmium level (U-Cd) was estimated in inhabitants whose initial U-Cd was a parts per thousand yen5 mu g/L (131 men and 177 women) or a parts per thousand yen5 mu g/gcr (195 men and 246 women), using a linear mixed model adjusted for the baseline age. To clarify the effect of initial U-Cd, the target participants were divided into higher or lower initial U-Cd group. In the higher groups, the half-lives were 15.4 and 13.1 years for unadjusted U-Cd and 19.0 and 23.0 years for creatinine-adjusted U-Cd, in men and women, respectively. In the lower groups, the half-lives were 38.0 and 26.0 years for unadjusted U-Cd in men and women. For creatinine-adjusted U-Cd, it was 42.9 years in men. For attenuation of U-Cd, there were an early fast component shown in the higher group and late slow component shown in the lower group. The attenuation of U-Cd is slower in the longer time compared to that previously reported.

Aims/Introduction: The present cohort study assessed the risk among Japanese men for developing type 2 diabetes, based on the percentage of energy intake from carbohydrates and degree of obesity. Participants and Methods: The participants were 2,006 male factory employees, and the macronutrient intake of each patient was measured using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual blood examinations over a 10-year period. Results: During the study, 232 participants developed diabetes. The crude incidence rates (/1,000 person-years) for different levels of carbohydrate intake as a percentage of calories consumed (&lt;50.0, 50.0-57.4, 57.5-65.0, &gt;65.0% of energy intake) were 16.5, 14.4, 12.7 and 17.6. Overall, carbohydrate intake was not associated with the risk of diabetes. However, there was significant interaction between carbohydrate intake and degree of obesity on the incidence of diabetes (P for interaction = 0.024). Higher carbohydrate intake was associated with elevated risk for diabetes among participants with a body mass index &gt;= 25.0 kg/m(2) (P for trend = 0.034). For obese participants, the multivariate-adjusted hazard ratio for those with carbohydrate intakes &gt;65% energy was 2.01 (95% confidence interval 1.08-3.71), which was significantly higher than that of participants with carbohydrate intakes 50.0-57.4% energy. Conclusions: Higher carbohydrate intake was associated with higher risk of diabetes in obese participants, but not in non-obese participants. Obese participants with carbohydrate intakes &gt;65% energy should reduce their intakes to levels within the desirable carbohydrate energy proportion for Japanese (50-65% energy) to prevent development of type 2 diabetes.

We investigated the biological half-life of urinary cadmium concentration (U-Cd) based on a 22-year follow-up study after cessation of environmental Cd pollution. Spot urine samples were obtained from the inhabitants (32 men and 36 women) in the target area in 1986, 1991, 1999, 2003 and 2008. These inhabitants were divided into higher or lower baseline U-Cd group by the cut-off of 5 mu gl(-1) or 5 mu gg(-1) creatinine. Biological half-life of U-Cd was estimated using a linear mixed model adjusted for the baseline age. In the higher baseline U-Cd groups, the estimated half-life and 95% confidence intervals were 12.4years (9.3-18.8years) and 11.4years (9.3-14.6years) for unadjusted U-Cd in men and women, respectively. For creatinine-adjusted U-Cd, they were 16.0years (13.0-20.7years) and 20.4years (16.6-26.2years) in men and women, respectively. In the lower baseline U-Cd groups, biological half-life for unadjusted U-Cd in men was solely significant (23.4years) and longer than the corresponding half-life in the higher baseline U-Cd group. The biological half-lives of U-Cd obtained in this study were identical with the values for U-Cd or total body burden determined by a different method.

The aim of this study was to establish the cause-effect relationship between renal tubular dysfunction and mortality. A 19-year cohort study was conducted in 900 men and 1313 women in 1993 or 1994 who lived in two cadmium non-polluted areas in Japan. Hazard ratio (HR) and 95% confidence interval (95% CI) of urinary beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-glucosaminidase (NAG) for mortality were calculated using a proportional hazard regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Simultaneously, the dose-effect relationship between renal tubular markers and urinary cadmium at baseline was evaluated using multiple regression analyses. In men, HR was significant for beta 2-MG (HR corresponding to an increase of 100 mu g/g cre: 1.02) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.05). In women, a significant HR was observed for beta 2-MG (HR corresponding to an increase of 100 mg/g cre: 1.01) and NAG (HR corresponding to an increase of 1 IU/g cre: 1.02). Dose-effect relationships were significant for urinary cadmium and all renal tubular markers in men and women. The present study indicated that renal tubular dysfunction was significantly related to mortality in the general population of cadmium non-polluted areas in Japan.

The aim of the present study was to evaluate the effect of environmental cadmium (Cd) exposure indicated by urinary Cd on all-cause mortality in the Japanese general population. A 19-year cohort study was conducted in 1067 men and 1590 women aged 50years or older who lived in three cadmium non-polluted areas in Japan. The subjects were divided into four quartiles based on creatinine adjusted U-Cd (mu gg(-1) cre). The hazard ratio (HR) and 95% confidence interval (CI) for continuous U-Cd or the quartiles of U-Cd were estimated for all-cause mortality using a proportional hazards regression.The all-cause mortality rates per 1000 person years were 31.2 and 15.1 in men and women, respectively. Continuous U-Cd (+1 mu gg(-1) cre) was significantly related to the all-cause mortality in men (HR 1.05, 95% CI: 1.02-1.09) and women (HR 1.04, 95% CI: 1.01-1.07). Furthermore in men, the third (1.96-3.22 mu gg(-1) cre) and fourth quartile (3.23 mu gg(-1) cre) of U-Cd showed a significant, positive HR (third: HR 1.35, 95% CI: 1.03-1.77, fourth: HR 1.64, 95% CI: 1.26-2.14) for all-cause mortality compared with the first quartile (&lt;1.14 mu gg(-1) cre). In women, the fourth quartile of U-Cd (4.66 mu gg(-1) cre) also showed a significant HR (1.49, 95% CI 1.11-2.00) for all-cause mortality compared with the first quartile (&lt;1.46 mu gg(-1) cre).In the present study, U-Cd was significantly associated with increased mortality in the Japanese general population, indicating that environmental Cd exposure adversely affects the life prognosis in Cd non-polluted areas in Japan. Copyright (c) 2014 John Wiley & Sons, Ltd.

The aim of this study was to estimate the reference level of cadmium in rice as the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for various renal effects by applying an updated hybrid approach. The participants were 1120 men and 1274 women aged 50 years or older who lived in the environmentally exposed Kakehashi river basin for at least 30 years. As indicators of renal dysfunction, glucose, protein, aminonitrogen, metallothionein and (2)-microgrobulin in urine were measured. Cadmium concentration was determined for rice samples stored in warehouses of the farmers in all of the polluted hamlets. The BMD and BMDL that corresponded to an additional risk of 5% were calculated with background risk at a zero exposure set at 5%. The obtained BMDLs were 0.39 (aminonitrogen), 0.26 (metallothionein), 0.25 ((2)-microgrobulin) mg kg(-1) in men and 0.44 (glucose), 0.32 (protein), 0.33 (aminonitrogen), 0.28 (metallothionein) and 0.24 ((2)-microgrobulin) mg kg(-1) in women. The lowest BMDL was 0.25 and 0.24 mg kg(-1) ((2)-microgrobulin) in men and women respectively. These values were lower than the maximum level (0.4 mg kg(-1)) determined by the Codex Alimentarius Commission, indicating that these BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure. Copyright (c) 2014 John Wiley & Sons, Ltd. We applied an updated hybrid approach to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of cadmium concentration in rice for renal effects in humans. The BMDL of cadmium in rice for 2-microglobulin was 0.25 mg/kg in men and 0.24 mg/kg in women. These estimated BMDLs may contribute to further discussion on the health risk assessment of cadmium exposure especially in terms of the food standard of cadmium concentration in rice.

We investigated the relation between overall sleep status based on the modified Pittsburgh Sleep Quality Index (PSQI) global score and subsequent changes in serum high-sensitivity C-reactive protein (hsCRP) in a population of Japanese factory workers, who were predominantly female. A total of 991 Japanese with inflammation classified as low cardiovascular risk (baseline hsCRP&lt;1.0mgL(-1)) were grouped according to the presence or absence of unfavourable sleep, defined as a modified PSQI global score&gt;5.5 points. The subsequent changes in hsCRP after 3years were then compared in the two groups. Analysis of covariance incorporating log-transformed baseline hsCRP, age, sex, lifestyle and physical and biochemical profiles was used to compare the geometric means of hsCRP at year 3 in each sleep status group. A logistic regression model incorporating the same variables was used to calculate the odds ratios for development of inflammation with a medium-to-high cardiovascular risk (hsCRP at year 31.0mgL(-1)) comparing the presence or absence of unfavourable sleep habits. The multivariate-adjusted geometric mean of hsCRP at year 3 was significantly higher in subjects with unfavourable sleep habits compared with those with a normal pattern (0.275 versus 0.242mgL(-1)). The multivariate-adjusted odds ratio for developing increased and potentially pathogenic levels of inflammation due to unfavourable sleep was 2.08 (95% confidence interval=1.29-3.35). There was a significant linear trend for the development of increased inflammation across the modified PSQI global scores (P=0.04). Unfavourable sleep is associated with activation of low-grade systemic inflammation.

Purpose: The aim of the present study was to evaluate the dose effect relationship between urinary cadmium (U-Cd as an index of internal Cd exposure) and mortality in a cohort of the Japanese general population. Methods: A 19-year cohort study was conducted in 897 men and 1307 women who lived in two non-polluted areas in Japan. The subjects were categorized into four quartiles based on creatinine adjusted UCd (11 mu g/g cre). Hazard ratio (HR) and 95% confidence interval (95%CI) of the quartiles of U-Cd for mortality was calculated using a proportional hazards regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness. Results: The mortality rates per 1000 person years were 27.8 and 12.5 in men and women, respectively. In men, the fourth quartile of U-Cd (&gt;= 2.919 mu g/g cre) showed a significant, positive HR (1.50, 95%CI: 1.11-2.02) for mortality compared to the first quartile (&lt;1.014). In women, the fourth quartile of U-Cd (&gt;= 3.943 mu g/g cre) also showed a significant HR (1.50, 95%CI: 1.08-2.09) for mortality compared to the first quartile (&lt;1.140). Conclusion: The present study clarified that U-Cd was significantly associated with increased mortality, indicating the worsened life prognosis of the general population in Cd non-polluted areas in Japan. These results highlight the importance of further discussion of the health risk assessment of Cd exposure in the general population. (C) 2014 Elsevier GmbH. All rights reserved.

Aims: To examine the relation of insulin resistant status determined by homeostasis model assessment of insulin resistance (HOMA-IR) with the risk of incident hyperuricemia. Methods: The study participants included 2071 Japanese men without hyperuricemia and diabetes, aged 35-54 years. The participants had undergone annual heath examinations for 6 years to compare incident hyperuricemia (serum uric acid &gt;416.4 mu mol/L (7.0 mg/dL) and/or taking medication for hyperuricemia) in four groups based on quartiles of baseline HOMA-IR. Results: During follow-up there were 331 incident cases of hyperuricemia. The hazard ratios for hyperuricemia, compared with HOMA-IR &lt;= 0.66, were 1.42 (95% confidence interval 1.02-1.98) for HOMA-IR 0.67-0.98, 1.20 (0.86-1.68) for HOMA-IR 0.99-1.49 and 1.44 (1.04-1.98) for HOMA-IR &gt;= 1.50 after adjustment for baseline serum uric acid, creatinine, hypercholesterolemia and hypertension status, age, alcohol intake, and smoking and exercise habits. The hazard ratio associated with an increase of one standard deviation in lnHOMA-IR (1.85 as one geometric standard deviation of HOMA-IR) was 1.14 (1.03-1.28) (p for trend = 0.02). Conclusions: Increased HOMA-IR independently predicted the subsequent development of hyperuricemia. Insulin resistance itself or compensatory hyperinsulinemia may contribute to the development of hyperuricemia. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background: Previous studies have shown that a diet with a high-glycemic index is associated with good sleep quality. Therefore, we investigated the association of sleep quality with the intake of 3 common starchy foods with different glycemic indexes-rice, bread, and noodles-as well as the dietary glycemic index in a Japanese population. Methods: The participants were 1,848 men and women between 20 and 60 years of age. Rice, bread, and noodle consumption was evaluated using a self-administered diet history questionnaire. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index, and a global score &gt;5.5 was considered to indicate poor sleep. Results: Multivariate-adjusted odds ratios (95% confidence intervals) for poor sleep across the quintiles of rice consumption were 1.00 (reference), 0.68 (0.49-0.93), 0.61 (0.43-0.85), 0.59 (0.42-0.85), and 0.54 (0.37-0.81) (p for trend = 0.015); those for the quintiles of noodle consumption were 1.00 (reference), 1.25 (0.90-1.74), 1.05 (0.75-1.47), 1.31 (0.94-1.82), and 1.82 (1.31-2.51) (p for trend = 0.002). Bread intake was not associated with sleep quality. A higher dietary glycemic index was significantly associated with a lower risk of poor sleep (p for trend = 0.020). Conclusion: A high dietary glycemic index and high rice consumption are significantly associated with good sleep in Japanese men and women, whereas bread intake is not associated with sleep quality and noodle consumption is associated with poor sleep. The different associations of these starchy foods with sleep quality might be attributable to the different glycemic index of each food.

Background: The aim of the present study was to estimate the benchmark doses (BMD) for renal effects for health risk assessment of residents living in Cd-polluted and non-polluted areas in a Thai population. Methods: The study participants consisted of inhabitants aged 40 years or older who lived in a non-polluted area (40 men and 41 women) and in the environmentally polluted Mae Sot District (230 men and 370 women) located in northwestern Thailand. We measured urinary and blood cadmium (Cd) as markers of long-term exposure and urinary beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) as renal tubular effect markers. An updated hybrid approach was applied to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) of urinary and blood Cd for Cd-induced renal effects in these subjects. BMD and BMDL corresponding to an additional risk (BMR) of 5% were calculated with the background risk at zero exposure set to 5% after adjusting for age and smoking status. Results: The estimated BMDLs of urinary Cd for renal effect markers were 6.9 for urinary beta 2-MG and 4.4 for NAG in men and 8.1 for beta 2-MG and 6.1 for NAG mu g/g creatinine (Creat) in women. These BMDLs of urinary Cd (mu g/g Creat) for NAG were less than the geometric mean urinary Cd in the polluted area (6.5 in men and 7.1 in women). The estimated BMDLs of blood Cd (mu g/L) were 6.2 for urinary beta 2-MG and 5.0 for NAG in men and 5.9 for beta 2-MG and 5.8 for NAG in women. The calculated BMDLs were similar or less compared with the geometric mean blood Cd (mu g/L) in the polluted Thai area (6.9 in men and 5.2 in women). Conclusion: The BMDLs of urinary and blood Cd for renal effects were estimated to be 4.4 - 8.1 mu g/g Creat and 4.4 -6.2 mu g/L in the Thai population aged &gt;= 40 years old, suggesting that more than 40% of the residents were at risk of adverse renal effects induced by Cd exposure in Thailand.

Background: We aimed to investigate the mortality and causes of deaths of inhabitants with renal dysfunction induced by cadmium (Cd) exposure caused by heavy environmental contamination. Methods: We conducted a 26-year follow-up survey targeting 7529 inhabitants of the Cd-polluted Jinzu River basin and 2149 controls from non-polluted areas who participated in urinary examinations for proteinuria and glucosuria conducted in 1979 to 1984. When the residents were divided into 4 groups, no finding group, glucosuria group, proteinuria group, glucoproteinuria group, mortality risk ratios for all and specific causes of these groups in the polluted area were compared with that of controls without glucosuria and/or proteinuria after adjustments for age at baseline, smoking status, and history of hypertension using Cox's proportional hazard model. Results: The mortality risk ratios for all causes of proteinuria and glucoproteinuria in men and glucosuria, proteinuria, and glucoproteinuria in women of the polluted areas significantly increased compared with those of the controls with no urinary findings. Respiratory, renal, and cardiovascular diseases and diabetes in men, and all diseases except cerebrovascular diseases in women contributed toward an increased mortality of exposed glucoproteinuria groups, which involved chronic Cd toxicosis with renal tubular dysfunction. In women, the mortality risks for cancer of the colon and rectum, uterus and kidney and urinary tract were significantly higher in the exposed proteinuria and glucoproteinuria groups, suggesting associations between renal damage and cancer risk. In exposed women, the no finding group and glucoproteinuria group also showed increased mortality from ischemic heart diseases, indicating that all exposed women may be at risk for ischemic heart diseases. Although the control glucosuria and/or proteinuria group also showed high mortality for diabetes and renal diseases, the increased risk ratio for renal disease mortality was much higher in exposed subjects with urinary findings, particularly in women. Conclusions: These findings indicate that inhabitants with renal effects caused by Cd exposure had a poor life prognosis over long-term observation in both genders. Particularly in women, renal tubular dysfunction indicated by glucoproteinuria may increase mortality from cancer, ischemic heart diseases, and renal diseases.

Objective This cross-sectional study investigated the associations between the serum thyroid-stimulating hormone (TSH) concentration and indices of obesity in middle-aged Japanese men and women. Methods The participants were 2,037 employees (1,044 men and 993 women; age, 36-55 yr) of a metal products factory in Japan. Clinical examinations were conducted in 2009. We obtained a medical history and anthropometric measurements (body weight, body mass index [BMI] and waist circumference) and measured the serum TSH concentrations. The anthropometric indices were compared across serum TSH quartiles. The associations were evaluated separately according to the smoking status in men. Results The mean body weight (kg), BMI (kg/m(2)) and waist circumference (cm) were 69.2, 23.7 and 83.2 in men and 55.3, 22.3 and 74.3 in women, respectively. Men with a higher TSH concentration had higher body weight and BMI values (p for trend=0.016 and 0.019, respectively), and these significant associations were observed even after adjusting for age, smoking status and other potential confounders. The TSH level was not associated with waist circumference. We found a significant interaction between the TSH level and the smoking status on body weight (p for interaction=0.013) and a significant association between the TSH level and body weight in nonsmokers, but not in current smokers. No significant associations were observed between the TSH level and the anthropometric indices in women. Conclusion Significant positive associations between the serum TSH concentration, body weight and BMI were detected in men only, and an interaction with the smoking status was observed for this association.

Background and purpose: The aim of this study was to clarify the relationship between occupational factors and the development of cerebral stroke in a large cohort working at a railway company in Japan. Methods: A 10-year prospective cohort study was conducted in 32,441 male workers who received annual health check-ups at a Japanese railway company. Diagnosis of cerebral stroke was based on the results of the annual health check-ups and individual medical histories. Cerebral stroke included cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage. The relationship between job type and the development of cerebral stroke was investigated using a proportional hazards regression with time-dependent covariates adjusted for age, body mass index, mean arterial pressure, family history of cerebral stroke, tobacco and alcohol consumption, and habitual exercise. Results: A negative relationship between job type and the development of cerebral stroke was observed in train crew members, with a significantly lower hazard ratio (HR) seen in train drivers (HR 0.63, 95% confidence interval (CI), 0.42-0.95) and conductors (HR 0.41, 95% CI, 0.24-0.71) in comparison to clerical workers. Conclusions: Since the present results were adjusted for various behavioral and biological factors, they suggest that train crew work itself is associated with a decreased risk of cerebral stroke. These results suggest that further studies on the effect of driving on health may provide information useful for the future prevention of cerebral stroke. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Background: The aim of this study was to examine the dose-response relationships between tobacco or alcohol consumption and the development of diabetes mellitus. Methods: An 8-year prospective cohort study was conducted in 8423 male workers who received annual health check-ups between 2002 and 2010 at a Japanese steel company. The endpoints were defined as an HbA(1c) &gt;= 6.1% or taking any anti-diabetic medication. The dose-response relationships of tobacco or alcohol consumption were investigated using a proportional hazards regression with time-dependent covariates selected from baseline age, body mass index, mean arterial pressure, total serum cholesterol, aspartate aminotransferase, creatinine and uric acid, shift work or day work, and habitual exercise by stepwise selection method. Results: A positive dose-response relationship between tobacco consumption and the development of diabetes mellitus was observed, with a significantly higher hazard ratio (HR) seen with higher tobacco consumption (11-20 cigarettes/day, HR 1.26 [95% confidence interval (CI), 1.00-1.59], &gt;= 21 cigarettes/day, HR 1.54 [95%CI, 1.20-1.971). In contrast, we observed a negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, with a significantly lower HR with higher weekly alcohol consumption (7.0-13.9 gou/week [154-307 g/week], HR 0.73 195% CI, 0.55-0.97], &gt;= 14.0 gou/week [308 g/week], HR 0.75 (95% CI, 0.57-0.98]). Conclusions: The results indicated that decreasing tobacco consumption will achieve significant prevention of diabetes mellitus. On the other hand, we observed a significant, negative dose-response relationship between alcohol consumption and the development of diabetes mellitus, in contrast to previous studies that reported a positive relationship in the Japanese population. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

PURPOSE: The aim of this study was to clarify the influence of shift work on serum total cholesterol (T-Cho) levels according to body mass index (BMI) at entry in Japanese male workers. METHODS: A 14-year prospective cohort study was conducted in day workers (n = 4079) and alternating shift workers (n = 2807) who received annual health check-ups between 1991 and 2005 in a Japanese steel company. The association between job schedule and increases in T-Cho was investigated using multivariate pooled logistic regression analyses with age, BMI, lifestyle (smoking habit, drinking habit, habitual exercise), and the results of blood chemistries (creatinine, glycosylated hemoglobin A1c, aspartic aminotransferase, gamma-glutamyl transpeptidase, uric acid) serving as covariates in those who were not overweight (BMI &lt; 25 kg/m(2), n = 5082) and overweight (BMI &gt;= 25 kg/m(2), n = 1804) at entry, respectively. The endpoints in the study were either a 20%, 25%, 30%, 35%, 40%, or 45% increase in T-Cho during the period of observation compared to T-Cho at entry. RESULTS: In subjects who were not overweight at entry, alternating shift work was associated significantly with five serum T-Cho endpoints (&gt;= 20%: odds ratio [OR] = 1.15, 95% confidence interval [CI)] = 1.05, 1.26; &gt;= 25%: OR = 1.17, 95% CI = 1.05, 1.31; &gt;= 35%: OR = 1.24, 95% CI = 1.05, 1.46; &gt;= 40%: OR = 1.30, 95% CI = 1.06, 1.61; &gt;= 45%: OR = 1.31, 95% CI = 1.01, 1.71). However, alternating shift work was not associated with any of the six T-Cho endpoints in subjects who were overweight at entry. CONCLUSIONS: In the present study, shift work was shown to be a potential risk factor for increased T-Cho in non-overweight Japanese male workers. However, we did not obtain a consistent association between shift work and an increase in T-Cho levels in overweight subjects. The results suggest that the effect of shift work on lipid regulation may be influenced by BMI. Ann Epidemiol 2011;21:327-335. (C) 2011 Elsevier Inc. All rights reserved.

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, beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-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%. Resuls and conclusions: The BMDL of U-Cd for renal effect markers were 2.1 (urinary protein), 2.6 (beta 2-MG) and 4.1 (NAG) mu g/g creatinine in men and 1.5 (urinary protein), 1.4 (beta 2-MG) and 3.1 (NAG) mu g/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. (C) 2010 Elsevier GmbH. All rights reserved.

Objectives: The aim of this study was to evaluate the reference level of urinary cadmium (Cd) that caused renal effects. An updated hybrid approach was used to estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL) in subjects with a wide range of exposure to Cd. Methods: The total number of subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397 men and 1706 women) in the environmentally exposed Kakehashi river basin. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and beta 2-microglobulin (beta 2-MG) as a marker of renal effects. The BMD and BMDL that corresponded to an additional risk (BMR) of 5% were calculated with background risk at zero exposure set at 5%. Results: The U-Cd BMDL for beta 2-MG was 3.5 mu g/g creatinine in men and 3.7 mu g/g creatinine in women. Conclusions: The BMDL values for a wide range of U-Cd were generally within the range of values measured in non-polluted areas in Japan. This indicated that the hybrid approach is a robust method for different ranges of cadmium exposure. The present results may contribute further to recent discussions on health risk assessment of Cd exposure. (C) 2010 Elsevier Inc. All rights reserved.

We used an updated hybrid approach to estimate the benchmark doses and their 95% lower confidence limits (BMDL) for cadmium-induced renal effects in humans. Participants were 828 inhabitants (410 men, 418 women), aged 40-59 years who lived in three areas without any known environmental cadmium pollution. We measured urinary cadmium (U-Cd) as a marker of exposure, and urinary protein, beta 2-microglobulin (beta 2-MG) and N-acetyl-beta-D-glucosaminidase (NAG) as markers of renal effects. For urinary protein, the BMDL ranged from 0.9 to 1.1 mu g g(-1) creatinine (cre) and approximately 1.6 mu g per 24 h in men, and from 1.9 to 3.4 mu g g(-1) cre and 2.0 mu g per 24 h in women. For the renal tubular markers beta 2-MG and NAG, the BMDL for U-Cd ranged from 0.6 to 1.2 mu g g(-1) cre and from 0.8 to 1.7 mu g per 24 h in men, and from 0.6 to 2.3 mu g g(-1) cre and from 0.6 to 2.1 mu g per 24 h in women. The lowest BMDL for urinary cadmium (0.6 mu g g-1 cre) was somewhat lower than average urinary cadmium in Japanese older population. These results suggest the importance of measures to decrease cadmium exposure in the general population of Japan. Copyright (C) 2010 John Wiley & Sons, Ltd.

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 &gt;= 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 (&gt;= 7.5%) and 16.9/19.4 yrs (&gt;= 10%). For workers aged &gt;= 50 yrs, the BMDL/BMD with a BMR of 5% was 22.9/28.2 yrs (&gt;= 7.5%) and 20.6/23.6 yrs (&gt;= 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).