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Aims: Data are limited regarding how shift work is linked to the development of type 2 diabetes, especially among workers at high risk of diabetes. We examined the risk of diabetes according to shift-work conditions over several years among Japanese adults. Methods: This prospective study enrolled 17,515 workers (age 40–78 years). Shift work was self-reported at annual health examinations over time from 2004 to 2017 and categorized as shift workers or non-shift workers. Diabetes was defined as fasting plasma glucose, random glucose, HbA1c, and self-reported use of antidiabetic medications. The association of shift work and diabetes was quantified using Cox regression. Results: During a follow-up of 8.1 years in median, 2071 incident cases of diabetes were documented. Compared with non-shift work, shift work showed a significantly elevated hazard ratios of developing diabetes. Shift work showed a 19% (95% confidence intervals: 3–37%) higher hazard ratios for diabetes, after adjustment for demographic-, cardiometabolic-, and work-related factors. Further adjustment for lifestyle factors and body mass index did not materially change this association (a 16% increase; 95% confidence intervals, 1–34%). This relationship was replicated among workers with prediabetes. Conclusions: Engaging in shift work may increase the risk of developing diabetes independently of lifestyle factors and body mass index, even among prediabetic workers. [ABSTRACT FROM AUTHOR]

Objective: Prediabetes has been suggested to increase risk for death; however, the definitions of prediabetes that can predict death remain elusive. We prospectively investigated the association of multiple definitions of prediabetes with the risk of death from all causes, cardiovascular disease (CVD), and cancer in Japanese workers.Research Design and Methods: The study included 62,785 workers who underwent a health checkup in 2010 or 2011 and were followed up for death from 2012 to March 2019. Prediabetes was defined according to fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c) values or a combination of both using the American Diabetes Association (ADA) or World Health Organization (WHO)/International Expert Committee (IEC) criteria. The Cox proportional hazards regression model was used to investigate the associations.Results: Over a 7-year follow-up, 229 deaths were documented. Compared with normoglycemia, prediabetes defined according to ADA criteria was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.53; 95% CI 1.12-2.09) and death due to cancer (HR 2.37; 95% CI 1.45-3.89) but not with death due to CVD. The results were materially unchanged when prediabetes was defined according to ADA FPG, ADA HbA1c, WHO FPG, or combined WHO/IEC criteria. Diabetes was associated with the risk of all-cause, CVD, and cancer deaths.Conclusions: In a cohort of Japanese workers, FPG- and HbA1c-defined prediabetes, according to ADA or WHO/IEC, were associated with a significantly increased risk of death from all causes and cancer but not CVD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: We previously developed a 3‐year diabetes risk score in the working population. The objective of the present study was to develop and validate flexible risk models that can predict the risk of diabetes for any arbitrary time‐point during 7 years. Materials and Methods: The participants were 46,198 Japanese employees aged 30–59 years, without diabetes at baseline and with a maximum follow‐up period of 8 years. Incident diabetes was defined according to the American Diabetes Association criteria. With routine health checkup data (age, sex, abdominal obesity, body mass index, smoking status, hypertension status, dyslipidemia, glycated hemoglobin and fasting plasma glucose), we developed non‐invasive and invasive risk models based on the Cox proportional hazards regression model among a random two‐thirds of the participants, and used another one‐third for validation. Results: The range of the area under the receiver operating characteristic curve increased from 0.73 (95% confidence interval 0.72–0.74) for the non‐invasive prediction model to 0.89 (95% confidence interval 0.89–0.90) for the invasive prediction model containing dyslipidemia, glycated hemoglobin and fasting plasma glucose. The invasive models showed improved integrated discrimination and reclassification performance, as compared with the non‐invasive model. Calibration appeared good between the predicted and observed risks. These models performed well in the validation cohort. Conclusions: The present non‐invasive and invasive models for the prediction of diabetes risk up to 7 years showed fair and excellent performance, respectively. The invasive models can be used to identify high‐risk individuals, who would benefit greatly from lifestyle modification for the prevention or delay of diabetes. [ABSTRACT FROM AUTHOR]

Aims: The control of blood glucose levels, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of diabetes complications; however, data are scarce on control status of these factors among workers with diabetes. The present study aimed to estimate the prevalence of participants with diabetes who meet glycated hemoglobin (HbA1c), BP, and LDL-C recommendations, and to investigate correlates of poor glycemic control in a large working population in Japan. Methods: The Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study is an ongoing cohort investigation, consisting mainly of employees in large manufacturing companies. We conducted a cross-sectional analysis of 3,070 employees with diabetes (2,854 men and 216 women) aged 20–69 years who attended periodic health examinations. BP was measured and recorded using different company protocols. Risk factor targets were defined using both American Diabetes Association (ADA) guidelines (HbA1c < 7.0%, BP < 140/90 mmHg, and LDL-C < 100 mg/dL) and Japan Diabetes Society (JDS) guidelines (HbA1c < 7.0%, BP < 130/80 mmHg, and LDL-C < 120 mg/dL). Logistic regression models were used to explore correlates of poor glycemic control (defined as HbA1c ≥ 8.0%). Results: The percentages of participants who met ADA (and JDS) targets were 44.9% (44.9%) for HbA1c, 76.6% (36.3%) for BP, 27.1% (56.2%) for LDL-C, and 11.2% (10.8%) for simultaneous control of all three risk factors. Younger age, obesity, smoking, and uncontrolled dyslipidemia were associated with poor glycemic control. The adjusted odds ratio of poor glycemic control was 0.58 (95% confidence interval, 0.46–0.73) for participants with treated but uncontrolled hypertension, and 0.47 (0.33–0.66) for participants with treated and controlled hypertension, as compared with participants without hypertension. There was no significant difference in HbA1c levels between participants with treated but uncontrolled hypertension and those with treated and controlled hypertension. Conclusion: Data from a large working population, predominantly composed of men, suggest that achievement of HbA1c, BP, and LDL-C targets was less than optimal, especially in younger participants. Uncontrolled dyslipidemia was associated with poor glycemic control. Participants not receiving antihypertensive treatment had higher HbA1c levels. [ABSTRACT FROM AUTHOR]

Objective: Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population. Methods: Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008–2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥126 mg/dl, random plasma glucose ≥200 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort. Results: The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703–0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883–0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715–0.753) and 0.882 (0.868–0.895), respectively. Participants with a non-invasive score of ≥15 and invasive score of ≥19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years. Conclusions: The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c. [ABSTRACT FROM AUTHOR]