Smoking Cessation, Weight Gain, and the Trajectory of Estimated Risk of Coronary Heart Disease: 8-Year Follow-up From a Prospective Cohort Study.

INTRODUCTION: The effect of weight gain following smoking cessation on cardiovascular risks is unclear. We aimed to prospectively investigate the association of weight gain following smoking cessation with the trajectory of estimated risks of coronary heart disease (CHD). METHODS: In a cohort of 18 562 Japanese male employees aged 30-64 years and initially free of cardiovascular diseases, participants were exclusively grouped into sustained smokers, quitters with weight gain (body weight increase ≥5%), quitters without weight gain (body weight increase <5% or weight loss), and never smokers. Global 10-year CHD risk was annually estimated by using a well-validated prediction model for the Japanese population. Linear mixed models and piecewise linear mixed models were used to compare changes in the estimated 10-year CHD risk by smoking status and weight change following smoking cessation. RESULTS: During a maximum of 8-year follow-up, both quitters with and without weight gain had a substantially decreased level of estimated 10-year CHD risk after quitting smoking, compared with sustained smokers (all ps for mean differences < .001). The estimated 10-year CHD risk within the first year after cessation decreased more rapidly in quitters without weight gain than in quitters with weight gain (change rate [95% confidence interval, CI] -0.90 [-1.04 to -0.75] vs. -0.40 [-0.60 to -0.19] % per year, p < .0001). Thereafter, the estimated 10-year CHD risk in both groups increased at similar rates (change rate [95% CI] -0.07 [-0.21 to 0.07] vs. 0.11 [-0.09 to 0.30] % per year, p = .16, from year 1 to year 2; and 0.10 [0.05 to 0.15] vs. 0.11 [0.04 to 0.18] % per year, p = .80, from year 2 to year 8). CONCLUSIONS: In this population of middle-aged, Japanese male workers, smoking cessation greatly reduces the estimated 10-year risk of CHD. However, weight gain weakens the beneficial effect of quitting smoking in a temporary and limited fashion. IMPLICATIONS: To the best of our knowledge, this study is the first to examine the effect of weight gain following smoking cessation on the trajectory of the absolute risk of CHD. Our data imply that the benefits of cessation for reducing the absolute risk of CHD outweigh the potential risk increase due to weight gain, and suggest that in order to maximize the beneficial effects of quitting smoking, interventions to control post-cessation weight gain might be warranted.

Smoking and Long-Term Sick Leave in a Japanese Working Population: Findings of the Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: Few studies have investigated the association between tobacco smoking and sick leave (SL) in Japan. METHODS: We followed 70 896 workers aged 20-59 years (60 133 males, 10 763 females) between April 2012 and March 2017. A Cox proportional hazards model was used to investigate the associations between smoking (smoking status and intensity) and long-term SL (ie, SL lasting ≥30 consecutive days). Cause-specific analyses were also conducted. RESULTS: A total of 1777 people took long-term SL during a follow-up of 307 749 person years. Compared with never-smokers, current smokers were at a higher risk of long-term SL (hazard ratio [HR] = 1.32; 95% confidence interval [CI] = 1.19 to 1.48). Cause-specific analyses revealed that current smoking was associated with a higher risk of SL due to all physical disorders (HR = 1.44, 95% CI = 1.22 to 1.69), cancer (HR = 1.49, 95% CI = 1.10 to 2.01), cardiovascular disease (CVD; HR = 2.16, 95% CI = 1.31 to 3.55), and injuries/external causes (HR = 1.83, 95% CI = 1.31 to 2.58). Former smokers were at a higher risk of SL due to cancer at a borderline significance level (HR = 1.38, 95% CI = 0.99 to 1.92). Low-intensity smoking (ie, 1-10 cigarettes smoked per day) was associated with all-cause SL, SL due to CVD, and SL due to injuries/external causes compared with never-smokers. CONCLUSION: In a large cohort of working-age Japanese, smoking was associated with a greater risk of long-term SL. Greater effort is needed to mitigate disease burden associated with smoking at workplace in Japan. IMPLICATIONS: Our study contributes to the literature on the association between smoking and SL in several ways. First, the study was conducted among a Japanese working population. While the association has been extensively studied in Western setting, few attempts have been made elsewhere. Second, cause-specific analyses were undertaken in our study. Third, we paid attention to the effect of low-intensity smoking on SL given that there is growing evidence of an elevated health risk associated with low-intensity smoking.

Smoking, Smoking Cessation, and the Risk of Hearing Loss: Japan Epidemiology Collaboration on Occupational Health Study.

INTRODUCTION: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. METHODS: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss. RESULTS: During follow-up, 3532 individuals developed high-frequency hearing loss, and 1575 developed low-frequency hearing loss. The hazard ratio (HR) associated with current smokers was 1.6 (95% confidence interval [CI] = 1.5 to 1.7) and 1.2 (95% CI = 1.1 to 1.4) for high- and low-frequency hearing loss, respectively, as compared with never smokers. The risk of high- and low-frequency hearing loss increased with the number of cigarettes smoked per day (both p for trend <.001). The HR associated with former smokers was 1.2 (95% CI = 1.1 to 1.3) and 0.9 (95% CI = 0.8 to 1.1) for high- and low-frequency hearing loss, respectively. The analysis by quitting years showed a decline in risk of hearing loss after quitting smoking, even among those who quitted less than 5 years before baseline. CONCLUSIONS: Smoking is associated with increased risk of hearing loss, especially at the high frequency, in a dose-response manner. The excess risk of hearing loss associated with smoking disappears in a relatively short period after quitting. IMPLICATIONS: The prospective association between smoking and hearing loss has not been well studied. To the best of our knowledge, our study is the largest to date investigating the association between smoking and incident hearing loss. Our results indicate that smoking is associated with increased risk of hearing loss in a dose-response manner. Quitting smoking virtually eliminates the excess risk of hearing loss, even among quitters with short duration of cessation. These results suggest that smoking may be a causal factor for hearing loss, although further research would be required to confirm this. If so, this would emphasize the need for tobacco control to prevent or delay the development of hearing loss.

Serum cholesterol levels preceding to suicide death in Japanese workers: a nested case-control study.

OBJECTIVE: To investigate the association between suicide death and serum cholesterol levels as measured at times close to suicide death. METHODS: We conducted a nested case-control study of 41 cases of suicide deaths and 205 matched controls with serum total cholesterol (TC) levels till 3 years before suicide death in a large cohort of Japanese workers. RESULTS: Individuals in the lowest versus highest tertile/predefined category of TC in a Japanese working population had a three- to four-fold greater risk of suicide death. Each 10 mg/dl decrement of average TC was associated with an 18% increased chance of suicide death (95% confidence interval, 2-35%). Similar results were found for TC levels at each year. CONCLUSION: These results suggest that a low serum TC level in recent past is associated with an increased risk of suicide death.

Metabolic Syndrome Over 4 Years Before the Onset of Cardiovascular Disease　- Nested Case-Control Study.

BACKGROUND: We investigated the risk of cardiovascular disease (CVD) with duration of metabolic syndrome (MetS) for the past 4 years before the CVD event.Methods and Results:We performed a nested case-control study within the Japan Epidemiology Collaboration on Occupational Health Study. A total of 139 registered cases of CVD and 561 self-reported cases of CVD were identified and matched individually on age, sex, and worksite with 695 and 2,803 controls, respectively. MetS was defined by the Joint Interim Statement definition. The odds ratio (95% confidence interval) for registered CVD was 4.7 (2.9, 7.5) for people with persistent MetS (positive for MetS for ≥3 assessments) and 1.9 (1.1, 3.3) for those with intermittent MetS (positive for MetS for 1-2 assessments), compared with people without MetS during the past 4 years before the event/index date (P for trend <0.001). The corresponding odds ratio for self-reported CVD was 2.7 (2.2, 3.5) and 1.8 (1.4, 2.3) (P for trend <0.001). The association with MetS duration was stronger for myocardial infarction than for other CVD subtypes. Similar results were obtained when using the Japanese MetS criteria. CONCLUSIONS: The risk of CVD increases with increasing MetS duration. These findings contribute to risk stratification and encourage lifestyle modification for people with MetS to minimize their health risk.

Smoking, Smoking Cessation, and Risk of Mortality in a Japanese Working Population　- Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: The effect of smoking on mortality in working-age adults remains unclear. Accordingly, we compared the effects of cigarette smoking and smoking cessation on total and cause-specific mortality in a Japanese working population. Methods and Results: This study included 79,114 Japanese workers aged 20-85 years who participated in the Japan Epidemiology Collaboration on Occupational Health Study. Deaths and causes of death were identified from death certificates, sick leave documents, family confirmation, and other sources. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated via Cox proportional hazards regression. During a maximum 6-year follow-up, there were 252 deaths in total. Multivariable-adjusted HRs (95% CIs) for total mortality, cardiovascular disease (CVD) mortality, and tobacco-related cancer mortality were 1.49 (1.10-2.01), 1.79 (0.99-3.24), and 1.80 (1.02-3.19), respectively, in current vs. never smokers. Among current smokers, the risks of total, tobacco-related cancer, and CVD mortality increased with increasing cigarette consumption (Ptrend<0.05 for all). Compared with never smokers, former smokers who quit <5 and ≥5 years before baseline had HRs (95% CIs) for total mortality of 1.80 (1.00-3.25) and 1.02 (0.57-1.82), respectively. CONCLUSIONS: In this cohort of workers, cigarette smoking was associated with increased risk of death from all and specific causes (including CVD and tobacco-related cancer), although these risks diminished 5 years after smoking cessation.

Cumulative Risk of Type 2 Diabetes in a Working Population: The Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: We estimated the cumulative risk of type 2 diabetes from age 30 to 65 years in a large working population in Japan. METHODS: We used data from the Japan Epidemiology Collaboration on Occupational Health Study. Participants (46,065 men and 7,763 women) were aged 30-59 years, free of diabetes at baseline, and followed up for a maximum of 7 years. Incident type 2 diabetes was defined based on fasting and casual glucose, glycated hemoglobin, and current medical treatment for type 2 diabetes. We calculated the sex-specific cumulative risk of type 2 diabetes using the Practical Incidence Estimator macro, which was created to produce several estimates of disease incidence for prospective cohort studies based on a modified Kaplan-Meier method. RESULTS: During 274,349 person-years of follow-up, 3,587 individuals (3,339 men and 248 women) developed type 2 diabetes. The cumulative risk was 34.7% (95% confidence interval, 33.1-36.3%) for men and 18.6% (95% confidence interval, 15.5-21.7%) for women. In BMI-stratified analysis, obese (BMI ≥30 kg/m2) and overweight (BMI 25-29.9 kg/m2) men and women had a much higher cumulative risk of type 2 diabetes (obese: 77.3% for men and 64.8% for women; overweight: 49.1% and 35.7%, respectively) than those with BMI <25 kg/m2 (26.2% and 13.4% for men and women, respectively). CONCLUSIONS: The present data highlight the public health burden of type 2 diabetes in the working population. There is a need for effective programs for weight management and type 2 diabetes screening, especially for young obese employees, to prevent or delay the development of type 2 diabetes.

Duration and degree of weight change and risk of incident diabetes: Japan Epidemiology Collaboration on Occupational Health Study.

We prospectively examined diabetes risk in association with a summary measure of degree and duration of weight change. The study participants were 51,777 employees from multiple companies in Japan, who were aged 30-59years, free of diabetes at baseline, and followed up for 7years (2008-2015). Exposure was cumulative body mass index (BMI)-years, which was defined as the area of BMI units above or below baseline BMI during follow-up, and was treated as a time-dependent variable in the Cox proportional hazards regression models. During the 263,539 person-years of follow-up, 3465 participants developed diabetes. The adjusted hazard ratio (HR) of diabetes for a 1-unit increase in cumulative BMI-years was 1.11 (95% confidence interval (CI): 1.09, 1.12). The association was more pronounced among overweight (HR=1.11; 95% CI: 1.08, 1.14) and obese (HR=1.12; 95% CI: 1.08, 1.15) adults compared with normal- and under-weight (HR=1.07; 95% CI: 1.03, 1.11) adults (P for interaction of cumulative BMI-years X baseline BMI-group=0.002). The association of higher cumulative BMI-years with incident diabetes did not substantially differ by metabolic phenotype. The present results emphasize the importance of avoiding additional weight gain over an extended period of time for the prevention of type 2 diabetes, especially among overweight and obese adults, irrespective of metabolic health status.

Metabolic syndrome components and diabetes incidence according to the presence or absence of impaired fasting glucose: The Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: We prospectively examined the association of diabetes risk with the number of metabolic abnormalities, as well as their combinations, according to the presence or absence of impaired fasting glucose (IFG) in a large-scale Japanese working population. METHODS: Participants included 55,271 workers at 11 companies who received periodic health check-ups between 2008 and 2013. The metabolic syndrome (MetS) components were defined using the 2009 Joint Interim Statement. IFG was defined as fasting plasma glucose 5.6-6.9 mmol/L. Diabetes newly diagnosed after the baseline examination was defined according to the American Diabetes Association criteria. We calculated the hazard ratios (HRs) for diabetes incidence using the Cox proportional hazards model. RESULTS: During the follow-up period (median 4.95 years), 3183 subjects developed diabetes. In individuals with normal fasting glucose levels, the risk of diabetes increased steadily with the increasing number of MetS components; the multivariable-adjusted HRs for incident diabetes for the number of MetS components were 2.0, 4.3, 7.0, and 10.0 for one, two, three, or four MetS components, respectively, compared with the absence of components. A similar association was observed among individuals with IFG; the corresponding HRs were 17.6, 23.8, 33.9, and 40.7. The combinations that included central obesity appeared to be more strongly associated with diabetes risk than other combinations with the same number of MetS components within the same glucose status. CONCLUSIONS: Our findings indicate that risk stratification of individuals by the presence or absence of IFG and the number of MetS components can detect individuals with a high risk of diabetes.

Age-, sex-, and diagnosis-specific incidence rate of medically certified long-term sick leave among private sector employees: The Japan Epidemiology Collaboration on Occupational Health (J-ECOH) study.

BACKGROUND: Long-term sick-leave is a major public health problem, but data on its incidence in Japan are scarce. We aimed to present reference data for long-term sick-leave among private sector employees in Japan. METHODS: The study population comprised employees of 12 companies that participated in the Japan Epidemiology Collaboration on Occupational Health Study. Details on medically certified sick-leave lasting ≥30 days were collected from each company. Age- and sex-specific incidence rate of sick-leave was calculated for the period of April 2012 to March 2014. RESULTS: A total of 1422 spells in men and 289 in women occurred during 162,989 and 30,645 person-years of observation, respectively. The three leading causes of sick-leave (percentage of total spells) were mental disorders (52%), neoplasms (12%), and injury (8%) for men; and mental disorders (35%), neoplasms (20%), and pregnancy-related disease (14%) for women. Incidence rate of sick-leave due to mental disorders was relatively high among men in their 20s-40s but tended to decrease with age among women. Incidence rate of sick-leave due to neoplasms started to increase after age 50 in men and after age 40 in women, making neoplasms the leading cause of sick-leave after age 50 for women and after age 60 for men and the second leading cause after age 40 for women and after age 50 for men. Pregnancy-related disease was the second leading cause of sick-leave among women aged 20-39 years. CONCLUSIONS: These results suggest that mental disorder, neoplasms, and pregnancy-related disease are the major causes of long-term sick-leave among private sector employees in Japan.

Optimal waist circumference cut-off points and ability of different metabolic syndrome criteria for predicting diabetes in Japanese men and women: Japan Epidemiology Collaboration on Occupational Health Study.

BACKGROUND: We sought to establish the optimal waist circumference (WC) cut-off point for predicting diabetes mellitus (DM) and to compare the predictive ability of the metabolic syndrome (MetS) criteria of the Joint Interim Statement (JIS) and the Japanese Committee of the Criteria for MetS (JCCMS) for DM in Japanese. METHODS: Participants of the Japan Epidemiology Collaboration on Occupational Health Study, who were aged 20-69 years and free of DM at baseline (n = 54,980), were followed-up for a maximum of 6 years. Time-dependent receiver operating characteristic analysis was used to determine the optimal cut-off points of WC for predicting DM. Time-dependent sensitivity, specificity, and positive and negative predictive values for the prediction of DM were compared between the JIS and JCCMS MetS criteria. RESULTS: During 234,926 person-years of follow-up, 3180 individuals developed DM. Receiver operating characteristic analysis suggested that the most suitable cut-off point of WC for predicting incident DM was 85 cm for men and 80 cm for women. MetS was associated with 3-4 times increased hazard for developing DM in men and 7-9 times in women. Of the MetS criteria tested, the JIS criteria using our proposed WC cut-off points (85 cm for men and 80 cm for women) had the highest sensitivity (54.5 % for men and 43.5 % for women) for predicting DM. The sensitivity and specificity of the JCCMS MetS criteria were ~37.7 and 98.9 %, respectively. CONCLUSION: Data from the present large cohort of workers suggest that WC cut-offs of 85 cm for men and 80 cm for women may be appropriate for predicting DM for Japanese. The JIS criteria can detect more people who later develop DM than does the JCCMS criteria.

Comparison of body mass index, waist circumference, and waist-to-height ratio for predicting the clustering of cardiometabolic risk factors by age in Japanese workers--Japan Epidemiology Collaboration on Occupational Health study.

BACKGROUND: Waist-to-height ratio (WHtR) has been suggested as a better screening tool than body mass index (BMI) and waist circumference (WC) for assessing cardiometabolic risk. However, most previous studies did not consider age. METHODS AND RESULTS: Participants were 45,618 men and 8,092 women aged 15-84 years who received periodic health checkups in 9 companies in Japan. Clustering of cardiometabolic risk factors was defined by the existence of 2 or more of high blood pressure, hyperglycemia, and dyslipidemia. In both men and women, unadjusted area under the curve (AUC) of the receiver-operating characteristic curve for WHtR in detecting the clustering of cardiometabolic risk factors was significantly higher than that for either BMI or WC; the AUCs for WHtR, BMI, and WC, respectively, were 0.734, 0.705, and 0.717 in men and 0.782, 0.762, and 0.755 in women. After adjustment for age, however, such differences were not observed; the corresponding values were 0.702, 0.701, and 0.696 in men. In women, the age-adjusted AUC for BMI was slightly higher than for other indices (WHtR, 0.721; BMI, 0.726; WC, 0.707). CONCLUSIONS: The screening performance of WHtR for detecting the clustering cardiometabolic risk factors was not superior to that of BMI.

Trajectories of body mass index and waist circumference before the onset of diabetes among people with prediabetes.

BACKGROUND & AIMS: To investigate trajectories of body mass index (BMI) and waist circumference (WC) among prediabetic people who progressed to diabetes, people who remained with prediabetes, and those who returned to normoglycemia. METHODS: We used data from 22,945 prediabetic people who received an annual health checkup for up to eight years. The development of diabetes was defined using the American Diabetes Association criteria. People who did not progress to diabetes during the observation period were classified as 'remained with prediabetes' or 'returned to normoglycemia', based on their last health checkup data. Trajectories of BMI and WC were evaluated using linear mixed models for repeated measures, with adjustment for a wide range of covariates. RESULTS: During the study period, 2972 people progressed to diabetes, 4706 returned to normoglycemia, and 15,267 remained with prediabetes. People who progressed to diabetes had a larger increase in mean BMI from 7 years to 1 year prior to diagnosis, which was about three times that of people who remained with prediabetes (annual change rate, 0.20 [95% confidence interval; 0.15 to 0.24] vs 0.06 [0.04 to 0.08] kg/m2 per year, P < 0.001), regardless of their BMI levels at the initial health checkup. Among people who returned to normoglycemia, mean BMI remained almost the same over time (-0.04 [-0.09 to 0.002] kg/m2 per year), except for those with obesity (-0.16 [-0.28 to -0.05] kg/m2 per year). As for WC, the annual change rate among people who developed diabetes was about 7 times that of people who remained with prediabetes (0.38 [0.32 to 0.45] vs 0.05 [0.03 to 0.08] cm per year, P < 0.001). We also observed a constant mean WC over time among people who had no central obesity and later returned to normoglycemia (-0.02 [-0.06 to 0.03] cm per year), and an annual decrease in mean WC among those who had central obesity and later returned to normoglycemia (-0.40 [-0.47 to -0.32] cm per year). CONCLUSIONS: Our study provides strong evidence that avoiding weight gain could help prediabetic people minimize the risk of developing diabetes, regardless of whether they are obese. Losing weight could help obese people restore normoglycemia from a prediabetic state, whereas maintaining current weight may help nonobese people return to normoglycemia.

Obesity and risk of hearing loss: A prospective cohort study.

BACKGROUND & AIMS: The existing yet limited prospective studies reported conflicting results about obesity and hearing loss. We investigated the prospective association between obesity and hearing loss in a large-scale Japanese working population, as well as the association between metabolic phenotype and hearing loss. METHODS: The study included 48,549 employees aged 20-64 years and free of hearing loss at baseline. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression was used to investigate the risk of hearing loss associated with body mass index (BMI) and metabolic phenotype (based on a BMI of ≥25.0/<25.0 kg/m2 and presence/absence of ≥2 components of metabolic syndrome, except waist circumference). Baseline and updated information were obtained from annual health checkups. RESULTS: With a median follow-up of 7 years, 1595 and 3625 individuals developed unilateral hearing loss at 1 and 4 kHz, respectively. The adjusted hazard ratios (HR) for hearing loss at 1 kHz were 1.21 (1.08, 1.36) and 1.66 (1.33, 2.08) for those with BMI 25.0-29.9 kg/m2 and BMI ≥30.0 kg/m2, respectively, compared to individuals with BMI <25.0 kg/m2. For hearing loss at 4 kHz, the corresponding HRs were 1.14 (1.05, 1.23) and 1.29 (1.09, 1.52). Compared with metabolically healthy non-obese individuals, the adjusted HRs for hearing loss at 1 kHz were 1.19 (1.03, 1.39), 1.27 (1.01, 1.61), and 1.48 (1.25, 1.76) for unhealthy non-obese, healthy obese, and unhealthy obese individuals, respectively. For hearing loss at 4 kHz, the corresponding HRs were 1.13 (1.04, 1.25), 1.21 (1.04, 1.41), and 1.26 (1.12, 1.41). CONCLUSIONS: Overweight and obesity are associated with an increased risk of hearing loss, and metabolically unhealthy obesity may confer additional risk.

Smoking cessation after long-term sick leave due to cancer in comparison with cardiovascular disease: Japan Epidemiology Collaboration on Occupational Health Study.

In occupational settings, smokers may take quitting smoking seriously if they experienced long-term sick leave due to cancer or cardiovascular disease (CVD). However, no study has elucidated the smoking cessation rate after long-term sick leave. We examined the smoking cessation rate after long-term sick leave due to cancer and CVD in Japan. We followed 23 survivors who experienced long-term sick leave due to cancer and 39 survivors who experienced long-term sick leave due to CVD who reported smoking at the last health exam before the leave. Their smoking habits before and after the leave were self-reported. Logistic regression was used to calculate adjusted smoking cessation rates. Smoking cessation rate after long-term sick leave due to cancer was approximately 70% and that due to CVD exceeded 80%. The adjusted smoking cessation rate was 67.6% (95% confidence interval [CI]: 47.0, 88.2) for cancer and 80.7% (95% CI: 67.7, 93.8) for CVD. Smoking cessation rate after a longer duration of sick leave (≥60 d) tended to increase for both CVD and cancer. Although any definite conclusion cannot be drawn, the data suggest that smoking cessation rate after long-term sick leave due to CVD is slightly higher than that for cancer.

Associations of anemia and hemoglobin with hemoglobin A1c among non-diabetic workers in Japan.

AIMS/INTRODUCTION: We examined the association between hemoglobin A1c (HbA1c) and anemia, which was categorized into three groups according to mean corpuscular volume (MCV), as well as the association between hemoglobin in the non-anemic range and HbA1c. MATERIALS AND METHODS: We used the 2016 health checkup data from 36,422 workers without diabetes. Anemic people were divided into three groups based on MCV: <80, 80-90 and >90 fL. Non-anemic people were divided into four groups based on their hemoglobin levels. We carried out multiple linear regression models to estimate the means and 95% confidence intervals (CIs) of HbA1c. RESULTS: For men, 0.2% had anemia with MCV <80 fL, 0.5% had anemia with MCV 80-90 fL, 0.9% had anemia with MCV >90 fL and 98.4% had no anemia. For women, the corresponding values were 6.1, 6.4, 2.8 and 84.7%, respectively. The adjusted mean HbA1c (%) values for men with anemia with MCV <80, 80-90 and >90 fL were 5.67 (95% CI 5.60-5.74), 5.58 (95% CI 5.54-5.62) and 5.41 (95% CI 5.37-5.44), respectively. Among men without anemia, HbA1c (%) increased from 5.36 (95% CI 5.34-5.39) in those with hemoglobin ≥17.5 mg/dL to 5.45 (95% CI 5.45-5.46) in those with hemoglobin 13.0 to <14.5 mg/dL (P for trend <0.001). The HbA1c values were higher in men with anemia with MCV <80 fL or MCV 80-90 fL, but lower in men with MCV >90 fL, compared with non-anemic men with hemoglobin 13.0 to <14.5 mg/dL (All P < 0.001). Similar findings were observed in women. CONCLUSIONS: We observed elevated HbA1c among anemic people with MCV <80 fL or MCV 80-90 fL, and decreased HbA1c among anemic people with MCV >90 fL, suggesting that different types of anemia might influence HbA1c differently. In addition, non-anemic people with lower hemoglobin levels had higher HbA1c levels, suggesting that hemoglobin levels are in need of consideration when interpreting HbA1c values among non-anemic people.

Five-year cumulative incidence of overweight and obesity, and longitudinal change in body mass index in Japanese workers: The Japan Epidemiology Collaboration on Occupational Health Study.

OBJECTIVE: The present study aimed to estimate cumulative incidence of overweight and obesity and describe 5-year longitudinal changes in body mass index (BMI) in a large occupational cohort in Japan. METHODS: Participants were 55 229 Japanese employees, who were aged 20-59 years and attended at all subsequent annual health check-ups between 2009 and 2014. Mixed model analysis was performed to examine the effects of age and cohort by gender on BMI change, with age as a random variable. Cumulative incidence of overweight (23.0≤ BMI <27.5 kg/m2 ) and obesity (BMI ≥27.5 kg/m2 ) was calculated. Logistic regression analysis was used to estimate odds ratios for the incidence of overweight and obesity according to age group. RESULTS: The incidence of overweight and obesity was approximately double in men (28.3% and 6.7%, respectively) compared to women (14.3% and 3.9%, respectively).The incidence of obesity decreased with age in men, but did not differ according to age in women (P for trend: .02 and .89, respectively). Among overweight participants, the incidence of obesity was higher in women (18.9%) than men (14.5%) and decreased with advancing age (P for trend: <.001 in men and .003 in women). Mean BMI was higher in men than women in all age groups throughout the period. Younger cohorts tended to have a higher BMI change compared with older cohorts. CONCLUSIONS: In this Japanese occupational cohort, transition from overweight to obesity is higher in women than men, and the more recent cohorts had a higher change in mean BMI than the older cohorts.

BMI and Medically Certified Long-Term Sickness Absence Among Japanese Employees.

OBJECTIVE: In contrast to the association between excess weight and sickness absence (SA), the association in relation to underweight has been under-researched. This study aimed to examine the effects of BMI at both extremes of its distribution on SA. METHODS: Data came from the Japan Epidemiology Collaboration on Occupational Health study of 77,760 workers aged 20 to 59 years (66,166 males, 11,594 females). Information was collected on medically certified long-term SA (LTSA) (i.e., SA lasting ≥ 30 consecutive days) from April 2012 to March 2017. A sex-specific Cox proportional hazards model was used to investigate the associations. RESULTS: Among males, both obesity (hazard ratio [HR] = 1.81, 95% CI: 1.50-2.17) and underweight (HR = 1.56, 95% CI: 1.23-1.96) were significantly associated with LTSA compared with normal weight. This U-shaped association between BMI categories and LTSA was observed both for mental and physical disorders. Among females, an elevated risk was observed among those with overweight (HR = 1.54, 95% CI: 1.16-2.05). CONCLUSIONS: In a cohort of the Japanese working-age population, both obesity and underweight were associated with a greater risk of LTSA in males. Future research should not overlook the excess risk of LTSA associated with underweight.

Association between anthropometric indices of obesity and risk of cardiovascular disease in Japanese men.

OBJECTIVES: We aimed to compare the association of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with risk of cardiovascular disease (CVD) among middle-aged working Japanese men. METHODS: A nested case-control study was performed among middle-aged male employees who underwent periodic health checkup. A total of 241 CVD cases were identified and matched individually on age, gender, and worksite with 1205 controls. Data on BMI, WC, WHtR, smoking, hypertension, diabetes, and dyslipidemia collected at 4 years before the event/index date were retrieved. Associations between BMI, WC, WHtR, and CVD risk were assessed by using conditional logistic regression models. RESULTS: The strength of the association of BMI, WC, and WHtR with CVD risk was similar. The smoking-adjusted odds ratio (95% confidence interval) for CVD was 1.60 (1.38-1.85), 1.53 (1.33-1.78), and 1.56 (1.35-1.81) for a 1 SD unit increase in BMI, WC, and WHtR respectively. After further adjustment for hypertension, diabetes, and dyslipidemia, these associations were attenuated but remained statistically significant. CONCLUSIONS: Measures of general (BMI) and abdominal (WC and WHtR) obesity were similarly associated with CVD in middle-aged Japanese men.

Low serum creatinine and risk of diabetes: The Japan Epidemiology Collaboration on Occupational Health Study.

AIMS/INTRODUCTION: We examined a prospective association between serum creatinine levels and diabetes. MATERIALS AND METHODS: The present study included 31,343 male workers without diabetes, and aged between 20 and 64 years at baseline. We calculated the cumulative average of their serum creatinine over the study period. We defined diabetes as either glycated hemoglobin levels ≥6.5%, random glucose levels ≥200 mg/dL, fasting glucose levels ≥126 mg/dL or receiving antidiabetic treatment. Cox proportional hazards regression analysis was carried out to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: With a median observation of 7.7 years, 2,509 participants developed diabetes. After adjusting for age, smoking, body mass index, hypertension and dyslipidemia, lower cumulative average serum creatinine levels were related to a greater diabetes risk: HRs were 1.56 (95% CI 1.35-1.82), 1.22 (1.09-1.35) and 1.06 (0.96-1.17) for the participants with serum creatinine <0.70, 0.70-0.79 and 0.80-0.89 mg/dL, respectively, compared with those with 0.90-1.20 mg/dL (P for trend <0.001). The serum creatinine-diabetes association was more pronounced among older adults (serum creatinine <0.70 vs 0.90-1.20 mg/dL, HR 1.66, 95% CI 1.37-2.00) than younger adults (HR 1.32, 95% CI 1.02-1.71; P for interaction by age group = 0.001). CONCLUSIONS: Low serum creatinine is associated with an increased risk of diabetes. Screening serum creatinine levels can be used to identify those who are at high risk of diabetes.