Effect of circadian rhythm type on serum lipid levels in shift workers: A 5-year cohort study.

We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness-Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the "definitely and moderately morning" group was -17.83 (95% confidence interval (CI): -33.42 to -2.23), and in the "intermediate 'group' was -16.84 [95% CI: -30.40 to -3.28], compared to the moderate evening type." The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness-Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the "moderately evening type" group, the regression coefficient in the "intermediate type" group was -16.08 (95% CI: -28.79 to -3.37), and in the "definitely and moderately morning type" group was -17.50 [95% CI: -32.11 to -2.88]. The "moderately evening type" group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels.

Benchmark dose of alcohol consumption for development of hyperuricemia in Japanese male workers: An 8-year cohort study.

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 ≥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.

Dose-response relationship between tobacco or alcohol consumption and the development of diabetes mellitus in Japanese male workers.

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(lc)≥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], ≥21 cigarettes/day, HR 1.54 [95%CI, 1.20-1.97]). 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 [95% CI, 0.55-0.97], ≥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.

The influence of being overweight on the relationship between shift work and increased total cholesterol level.

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, γ-glutamyl transpeptidase, uric acid) serving as covariates in those who were not overweight (BMI < 25 kg/m(2), n = 5082) and overweight (BMI ≥ 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 (≥20%: odds ratio [OR] = 1.15, 95% confidence interval [CI)] = 1.05, 1.26; ≥25%: OR = 1.17, 95% CI = 1.05, 1.31; ≥35%: OR = 1.24, 95% CI = 1.05, 1.46; ≥40%: OR = 1.30, 95% CI = 1.06, 1.61; ≥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.

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.

Calculation of the benchmark duration of shift work associated with the development of impaired glucose metabolism: a 14-year cohort study on 7104 male workers.

OBJECTIVES: The aim of this study was to calculate the benchmark doses (BMD) and their 95% lower confidence boundary (BMDL) for the threshold number of years of shift work associated with a relative increase in haemoglobin A1c (HbA(1c)), an index of glucose metabolism. METHODS: A 14-year prospective cohort study was conducted in male workers at a Japanese steel company (n=7104) who had received annual health check-ups between 1991 and 2005. The endpoints were either a 10%, 15%, 20%, 25% or 30% increase in HbA(1c) levels during the observation period, compared to HbA(1c) at entry to the study. The associations between years of shift work and increases in HbA(1c) were investigated using pooled logistic regression, adjusted for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habits, smoking habits and habitual exercise. RESULTS: The BMDL/BMD for years of shift work were calculated using benchmark responses (BMRs) of 5% or 10% and parameters for duration of shift work and other covariates. Assuming a mean age of 53 years in workers aged 50 years or older, the BMDL/BMD for years of shift work with a BMR of 5% were 17.8/23.9 (> or = 15%), 15.7/18.7 (> or = 20%), 18.9/22.7 (> or = 25%) and 25.2/31.7 (> or = 30%). With a BMR of 10%, the respective values were 29.5/39.7 (> or = 15%), 24.3/28.9 (> or = 20%), 27.3/32.7 (> or = 25%) and 34.1/42.9 (> or = 30%). CONCLUSION: These results suggest that special attention should be paid to middle-aged workers whose years of shift work exceeds these threshold times.

Longitudinal effect of smoking cessation on physical and laboratory findings.

BACKGROUND: Detailed information on the expected physiologic changes after smoking cessation is practically useful to encourage people to stop smoking. Furthermore, weight increase after cessation may affect such physiologic changes. PURPOSE: This article aims to evaluate the effect of smoking cessation on annual changes in body weight, blood pressure, and blood biochemistry. METHODS: This study analyzed the results of annual health examinations from 1991 to 2005 in male Japanese workers in 2009. Subjects classified as stopping smoking (n=445) responded initially as smokers in a self-administered questionnaire (baseline year) and then answered consistently as nonsmokers for 3 subsequent years. Of the 2672 smokers identified in the study, 2403 subjects who had data available for at least 4 successive years were selected as controls. The time course of physiologic and laboratory data was analyzed using a linear mixed model. RESULTS: Data adjusted for age, type of job schedule, drinking and physical activity showed that subjects who stopped smoking had significantly greater increases in weight, BMI, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and uric acid and a greater decrease in hemoglobin in the 3 years following smoking cessation than continuing smokers. Additional adjustment for change in BMI from baseline negated the significant deterioration in systolic and diastolic blood pressure and total cholesterol that occurred following smoking cessation. CONCLUSIONS: Increase in body weight, blood pressure, and blood biochemistry can continue for at least 3 years after smoking cessation. This study also indicated that these increases were related to the weight increase that occurred after smoking cessation.

Estimation of the benchmark duration of alternating shift work associated with increased total cholesterol levels among male Japanese workers.

OBJECTIVE: The aim of this study was to estimate the benchmark doses (BMD) and their 95% lower confidence limits (BMDL) for the threshold number of years of alternating shift work associated with a relative increase in serum total cholesterol level (T-Cho), as an index of lipid metabolism. METHODS: We conducted a 14-year prospective cohort study among male workers (N=6886) at a Japanese steel company who had received annual health check-ups between 1991 and 2005. The endpoints were either a 20, 25, 30, 35, 40 or 45% increase in T-Cho levels during the observation period, compared to T-Cho at baseline. We investigated the associations between the years of alternating shift work and the relative increases in T-Cho using pooled logistic regression, adjusted for other potential covariates. RESULTS: We estimated the BMDL and BMD for years of alternating shift work among 40-, 50-, or >50-year old subjects using benchmark responses (BMR) of 5 or 10% and parameters for the duration of alternating shift work and other covariates. Assuming a mean age of 44 years among workers in their 40s, the BMDL/BMD for years of alternating shift work with a BMR of 5% were 21.0/28.0 (> or =20%), 21.3/26.1 (> or =25%), 24.1/28.8 (> or =30%), 25.6/29.8 (> or =35%), 27.1/31.5 (> or =40%), and 27.7/32.1 (> or =45%). CONCLUSIONS: The threshold number of years of alternating shift work that caused a 5% increase in T-Cho was shown to be > or =21 years among middle-aged workers. Special attention should be paid to influence the process at an earlier stage and not when the risk has already materialized.

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, gamma-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 (> or =10% HbA1c increase, odds ratio 1.35 [95% confidence interval 1.26-1.44]; > or =15% HbA1c increase, odds ratio 1.29 [95% confidence interval, 1.19-1.40]; > or =20% HbA1c increase, odds ratio 1.23 [95% confidence interval 1.11-1.37]; and > or =25% HbA1c increase, odds ratio 1.19 [95% confidence interval 1.03-1.36]). Age, body mass index, alanine aminotransferase, and gamma-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.

Longitudinal evaluation of the effect of smoking initiation on body weight, blood pressure, and blood biochemistry.

OBJECTIVE: To evaluate the effect of smoking initiation on annual changes in body weight, blood pressure, and blood biochemistry. METHODS: This study analyzed the results of annual health examinations from 1991 to 2005 in male Japanese workers. Subjects who started smoking (n=214) initially responded as non-smokers in a self-administered questionnaire (baseline year) and then answered consistently as smokers for 3 subsequent years. Out of 2547 non-smokers, we selected 1589 controls who had data available for at least four successive years. The time course of physiological and laboratory data was analyzed using a linear mixed model. RESULTS: A significant temporal decrease from baseline in body mass index (first year, -0.1 kg/m(2)), diastolic blood pressure (second year, -1.5 mm Hg) and gamma-glutamyl transpeptidase (second year, -3.5 IU/L) was observed for subjects who started smoking. An opposite pattern was observed in non-smokers. On average, those who started smoking had significantly lower body mass index (first year, -0.2 kg/m(2); second year, -0.2 kg/m(2)), systolic blood pressure (second year, -2.1 mm Hg), diastolic blood pressure (second year, -2.0 mm Hg), and gamma-glutamyl transpeptidase (second year, -4.5 IU/L) than non-smokers. CONCLUSION: In this study, smoking initiation did not yield clinically significant long-term benefits with respect to physiological or biochemical outcomes. These results are important because few studies have tracked these types of changes longitudinally from initiation through 3 years of follow-up.

Smoking as an independent risk factor for hypertension: a 14-year longitudinal study in male Japanese workers.

There have been few large longitudinal studies on the relationship between smoking and blood pressure and those results have been inconsistent. The aim of this study was to clarify the influence of smoking on the onset of hypertension. A 14-year longitudinal study was conducted in Japanese male workers at a steel company between 1991 and 2005. We adopted three different endpoints of observation, hypertension [systolic blood pressure (SBP) >or= 140 mmHg and diastolic blood pressure (DBP) >or= 90 mmHg], systolic hypertension (SBP >or= 140 mmHg), and diastolic hypertension (DBP >or= 90 mmHg), with initiation of antihypertensive medication. The cohort for each endpoint (hypertension: n = 5,512, systolic hypertension: n = 5,765, diastolic hypertension: n = 6,063) was selected, excluding the subjects whose blood pressure was higher than above criteria at their first health examination from all 8,251 workers. The strict criteria for hypertension resulted in exclusion of more subjects, yielding smaller cohort for hypertension. The association between smoking and each endpoint was investigated adjusting for age, body mass index, drinking, habitual exercise, job schedule type, hemoglobin A1c, total cholesterol, creatinine, aspartic aminotransferase, gamma-glutamyl transpeptidase, and uric acid by pooled logistic regression analyses. The significant odds ratios (and 95% confidence intervals) of smoking were 1.13 (1.03 to 1.23) for hypertension and 1.15 (1.05 to 1.25) for systolic hypertension. This study revealed that smoking is independently related to the onset of hypertension and systolic hypertension in Japanese male workers. These results provide important information necessary to define the effect of smoking on blood pressure.

Benchmark duration of work hours for development of fatigue symptoms in Japanese workers with adjustment for job-related stress.

The objective of this study was to calculate benchmark durations and lower 95% confidence limits for benchmark durations of working hours associated with subjective fatigue symptoms by applying the benchmark dose approach while adjusting for job-related stress using multiple logistic regression analyses. A self-administered questionnaire was completed by 3,069 male and 412 female daytime workers (age 18-67 years) in a Japanese steel company. The eight dependent variables in the Cumulative Fatigue Symptoms Index were decreased vitality, general fatigue, physical disorders, irritability, decreased willingness to work, anxiety, depressive feelings, and chronic tiredness. Independent variables were daily working hours, four subscales (job demand, job control, interpersonal relationship, and job suitability) of the Brief Job Stress Questionnaire, and other potential covariates. Using significant parameters for working hours and those for other covariates, the benchmark durations of working hours were calculated for the corresponding Index property. Benchmark response was set at 5% or 10%. Assuming a condition of worst job stress, the benchmark duration/lower 95% confidence limit for benchmark duration of working hours per day with a benchmark response of 5% or 10% were 10.0/9.4 or 11.7/10.7 (irritability) and 9.2/8.9 or 10.4/9.8 (chronic tiredness) in men and 8.9/8.4 or 9.8/8.9 (chronic tiredness) in women. The threshold amounts of working hours for fatigue symptoms under the worst job-related stress were very close to the standard daily working hours in Japan. The results strongly suggest that special attention should be paid to employees whose working hours exceed threshold amounts based on individual levels of job-related stress.

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 >or=10%, >or=15%, >or=20%, >or=25%, or >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, gamma-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: >or=10%, 1.15 (1.07 to 1.23); >or=15%, 1.21 (1.12 to 1.31); >or=20%, 1.15 (1.04 to 1.28); >or=25%, 1.20 (1.06 to 1.37); and >or=30%, 1.23 (1.03 to 1.47) for systolic blood pressure and >or=10%, 1.19 (1.11 to 1.28); >or=15%, 1.22 (1.13 to 1.33); >or=20%, 1.24 (1.13 to 1.37); and >or=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.

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. METHODS AND PROCEDURES: A longitudinal cohort study was conducted in day workers (n = 4,328) and alternating shift workers (n = 2,926) of a steel company who received annual health checkups over a 14-year period between 1991 and 2005. The association between the type of job schedule and weight gain was investigated using multivariate pooled logistic regression analyses. The endpoints in the study were either a 5, 7.5, or 10% increase in BMI during the period of observation, compared to the BMI at entry. RESULTS: The type of job schedule was significantly associated with all three BMI endpoints (5% increase in BMI; odds ratio (OR) for comparison between alternating shift workers and regular day workers, 1.14; 95% confidence interval (CI), 1.06-1.23): (7.5% increase in BMI; OR, 1.13; 95%CI, 1.03-1.24: 10% increase in BMI; OR, 1.13; 95%CI, 1.00-1.28). BMI at study entry was also positively associated with the 5, 7.5, and 10% increases in BMI during the study. On the other hand, age and drinking habits were negatively associated with 5, 7.5, and 10% increases in BMI. DISCUSSION: Our study revealed that alternating shift work was an independent risk factor for weight gain in male Japanese workers. Efficient health screening and regular checkups, combined with support to control unhealthy lifestyle factors, would be of considerable benefit for maintaining the health of Japanese shift workers.

Relationship between shift work and hypercholesterolemia in Japan.

OBJECTIVES: The objective of this study was to clarify the influence of shift work on total cholesterol levels in serum in male Japanese workers. METHODS: Pooled logistic regression analyses were applied in this 14-year cohort study of 5510 male workers in a steel company. In examining how the adjustments influenced the results, the effect of shift work on the onset of hypercholesterolemia (>or=220 mg/dl, 5.7 mmol/l) was calculated by adjusting only for age (step 1), for age and lifestyle factors (drinking habit, smoking habit, habitual exercise) (step 2), for age, body mass index (BMI), and the laboratory data [creatinine, glycosylated hemoglobin A1c (HbA1c), aspartic aminotransferase, gamma-glutamyl transpeptidase (gamma-GTP), uric acid] (step 3), and for age, BMI, lifestyle factors, and the laboratory data (step 4). RESULTS: The odds ratio (OR) for shift work with respect to the onset of hypercholesterolemia was significant in step 4 [OR 1.10, 95% confidence interval (95% CI) 1.00-1.21, P-value 0.048], whereas the corresponding odds ratios in steps 1, 2, and 3 were not significant. In step 4, the other significant covariates were age (OR 1.01, 95% CI 1.00-1.02), BMI (OR 1.07, 95% CI 1.05-1.09), HbA1c (OR 1.07, 95% CI 1.02-1.11), gamma-GTP (OR 1.03, 95% CI 1.02-1.04) and alcohol consumption (OR 0.89, 95% CI 0.81-0.99). CONCLUSIONS: In the present study, shift work was shown to be a potential risk factor for hypercholesterolemia among male Japanese workers. However, no consistent association was found between shift work and hypercholesterolemia in the hierarchical evaluation of the statistical model. The present study could not provide well-established evidence for a relationship between shift work and hypercholesterolemia.