Association between an Antioxidant-Rich Japanese Diet and Chronic Kidney Disease: The Ohasama Study.

AIMS: Although physiological effects of hydrophilic- (H-) and lipophilic- (L-) antioxidant capacities (AOCs) are suggested to differ, the association of an antioxidant-rich diet and chronic kidney disease (CKD) incidence has not been examined. We therefore explored the association between the H- or L-AOC of a whole Japanese diet and CKD risk in a general population. METHODS: A total of 922 individuals without CKD (69.2% women; mean age, 59.5 years old) from Ohasama Town, Japan, were examined. CKD incidence was defined as the presence of proteinuria and/or an estimated glomerular filtration rate (eGFR) of ＜60 ml/min/1.73 m2. Consumption of H-/L-AOC was determined based on the oxygen radical absorbance capacity in a specially developed Japanese food AOC database. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for new-onset CKD using a Cox proportional hazards model. RESULTS: During the median follow-up of 9.7 years, 137 CKD incidents were recorded. After adjusting for potential confounding variables, the highest quartile of L-AOC was significantly associated with a 51% reduced CKD risk among only women. An increased L-AOC intake was more effective in preventing eGFR reduction than in preventing proteinuria in women. These associations were not seen for H-AOC intake in both sexes and L-AOC intake in men. CONCLUSIONS: A high intake of lipophilic antioxidants may be associated with a reduced CKD risk. The balance between dietary antioxidant intake and pro-oxidants induced by unhealthy lifestyles may be crucial for preventing future kidney deterioration.

Offering on-site mammography in workplaces improved screening rates: Cluster randomized controlled trial.

OBJECTIVES: Despite evidence of breast cancer screening efficacy, the screening rate has remained less than 50% in Japan. This study aimed to evaluate the effect of an environmental approach offering on-site mammography in workplaces. METHODS: Supermarket stores were randomly assigned into two groups, the intervention group (leaflet and mammography) and the control group (leaflet). From May to July 2018, participants in the intervention group were given a leaflet informing them of the subsidies for breast cancer screening and offered the opportunity to have mammography in their workplaces. Participants in the control group were given the same leaflet, but had to arrange their own screening outside the workplace. The primary outcome was the breast cancer screening rate in 2018. The odds ratio (OR) and 95% confidence interval (CI) for having screening in the intervention group compared with the control group were estimated using multilevel logistic regression. RESULTS: We analyzed data from 1624 participants (mean age 53 years) from 25 supermarket stores (intervention: 8 stores, control: 17 stores). Among participants who had not attended screening in the previous year, the screening rate was 7% in the control group and 53% in the intervention group, with an adjusted OR (95% CI) of 14.22 (8.97-22.54). The effect was greater in those who had never attended screening before. CONCLUSION: In a worksite-based cluster randomized controlled trial in Japanese supermarket stores, an environmental approach offering mammography in workplaces substantially increased the breast cancer screening rate within 1 year (UMIN000030465).

Association Between Ambulatory Blood Pressure and Risk of Home Hypertension in a Normotensive Population: The Ohasama Study.

BACKGROUND: We investigated the association between ambulatory blood pressure (BP) and the risk of home hypertension in a normotensive population and whether considering ambulatory BP improves the 10-year prediction model for home hypertension risk, which was developed in the previous Ohasama Study. METHODS: In this prospective study, we followed up with 410 participants (83.2% women; age, 53.6 years) without a home and ambulatory hypertension in the general population of Ohasama, Japan. The Cox model was used to assess the hazard ratios (HRs) for home hypertension (home BP ≥ 135/≥85 mmHg or the initiation of antihypertensive treatment) and model improvement. RESULTS: During a mean 14.2-year follow-up, 225 home hypertension incidences occurred. The HR (95% confidence interval) for home hypertension incidence per 1-SD higher (=6.76 mmHg) 24-hour systolic BP (SBP) was 1.59 (1.33 to 1.90), after adjustments for possible confounding factors, including baseline home SBP. Harrell's C-statistics increased from 0.72 to 0.73 (P = 0.11) when 24-hour SBP was added to the basic 10-year home hypertension prediction model, which includes sex, age, body mass index, smoking status, office SBP, and baseline home SBP. Continuous net reclassification improvement (0.53, P < 0.0001) and integrated discrimination improvement (0.028, P = 0.0014) revealed improvement in the model. CONCLUSIONS: A total of 24-hour SBP could be an independent predictor of future home hypertension. Home BP and 24-hour BP can longitudinally influence each other in the long term.

Female Reproductive Events and Subclinical Atherosclerosis of the Brain and Carotid Arteriopathy: the Ohasama Study.

AIMS: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy. METHODS: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates. RESULTS: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992-2008 or 1993-2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries. CONCLUSIONS: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.

Prediction Models for the 5- and 10-Year Incidence of Home Morning Hypertension: The Ohasama Study.

BACKGROUND: We aimed to develop risk prediction models for new-onset home morning hypertension. METHODS: We followed up 978 participants without home hypertension in the general population of Ohasama, Japan (men: 30.1%, age: 53.3 years). The participants were divided into derivation (n = 489) and validation (n = 489) cohorts by their residential area. The C-statistics and calibration plots were assessed after the 5- or 10-year follow-up. RESULTS: In the derivation cohort, sex, age, body mass index, smoking, office systolic blood pressure (SBP), and home SBP at baseline were selected as significant risk factors for new-onset home hypertension (≥135/85 mm Hg or the initiation of antihypertensive treatment) using the Cox model. In the validation cohort, Harrell's C-statistic for the 5-/10-year home hypertension was 0.7637 (0.7195-0.8100)/0.7308 (0.6932-0.7677), when we used the full model, which included the significant risk factors in the derivation cohort. The calibration test revealed good concordance between the observed and predicted 5-/10-year home hypertension probabilities (P ≥ 0.19); the regression slope of the observed probability on the predicted probability was 1.10/1.02, and the intercept was -0.04/0.06, respectively. A model without home SBP was also developed; for the 10-year home hypertension risk, the calibration test revealed a good concordance (P = 0.19) but Harrell's C-statistic was 0.6689 (0.6266-0.7067). CONCLUSIONS: The full model revealed good ability to predict the 5- and 10-year home morning hypertension risk. Although the model without home SBP is acceptable, the low C-statistic implies that home BP should be measured to predict home morning hypertension precisely.

Higher serum uric acid level is inversely associated with renal function assessed by cystatin C in a Japanese general population without chronic kidney disease: the KOBE study.

BACKGROUND: Although several epidemiological studies have suggested that high serum uric acid (SUA) levels are related to a decline in kidney function, only a few studies have investigated using cystatin C to calculate estimated glomerular filtration rate (eGFR). We aimed to clarify the relationship between SUA levels and kidney function assessed by cystatin C in a Japanese general community population without chronic kidney disease (CKD). METHODS: We conducted a community-based cross-sectional study that included 1086 healthy participants, aged 40-74 years, without CKD and not undergoing treatment of hyperuricemia, who had participated in the baseline survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. The preconditions for participation in this study were no past histories of cardiovascular disease or cancer, and not undergoing treatment for diabetes, hypertension, or dyslipidemia. We classified the participants into quartiles stratified by sex according to their SUA level and then examined the relationship with eGFR. The odds ratios for having a low eGFR, defined as the lowest quartile of eGFR (i.e., ≤78.4 mL/min/1. 73m2) was estimated according to SUA quartiles (men, Q1 ≤ 5.0, Q2 5.1-5.9, Q3 6.0-6.6, and Q4 ≥ 6.7; women, Q1 ≤ 3.8, Q2 3.9-4.3, Q3 4.4-4.9, and Q4 ≥ 5.0 mg/dL) after adjustment for age, body mass index, systolic blood pressure, HbA1c, high and low density lipoprotein cholesterol, and smoking and drinking habits. The adjusted mean of each quartile was also calculated. RESULTS: Multivariable-adjusted means of eGFR showed a graded decrease in higher SUA quartiles (men, Q1 90.5, Q2 88.0, Q3 83.5, and Q4 82.0; women, Q1 95.7, Q2 91.3, Q3 89.2, and Q4 86.7). In addition, the multivariable-adjusted odds ratios for having a lower eGFR (95% confidence interval) for each SUA quartile compared with Q1 was Q2 2.29 (0.98, 5.35), Q3 4.94 (2.04, 11.97), and Q4 8.01 (3.20, 20.04) for men, and was Q2 2.20 (1.12, 4.32), Q3 2.68 (1.39, 5.20), and Q4 4.96 (2.62, 9.41) for women. CONCLUSIONS: There was a graded inverse relationship between mild elevations in SUA levels and eGFR assessed by cystatin C in an apparently healthy Japanese population without CKD. This association was similar in both men and women.

A prospective study of the impact of diabetes mellitus on restrictive and obstructive lung function impairment: The Saku study.

BACKGROUND: To assess the impact of diabetes on restrictive and obstructive lung function impairment. METHODS: This 5-year prospective study included 7524 participants aged 40-69years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥7.0mmol/l (126mg/dl), HbA1c≥6.5% (48mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) <80% predicted and forced expiratory volume in 1s (FEV1) to FVC ratio (FEV1/FVC) <0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014. RESULTS: During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04-2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72-1.21)]. CONCLUSION: Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment.

Risk of proteinuria among individuals with persistent borderline diabetes: the Saku study.

OBJECTIVE: To investigate the risk of decreased estimated glomerular filtration rate (eGFR) and proteinuria among individuals with borderline diabetes. METHODS: This 5-year cohort study involved 2849 participants aged 30-79 years without diabetes or chronic kidney disease at baseline (April 2008-March 2009). Participants were categorized into two groups-normoglycemia and borderline diabetes-based on the results of a 75-g oral glucose tolerance test at baseline. Participants underwent annual comprehensive medical check-ups during the follow-up period until March 2014. Main outcomes were defined as proteinuria ≥[1+] or eGFR <60 ml/min/1.73 m2. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) of eGFR <60 ml/min/1.73 m2 and proteinuria ≥[1+] for the borderline diabetes group compared with the normoglycemia group. RESULTS: During the follow-up period, 335 individuals developed eGFR <60 ml/min/1.73 m2 and 136 individuals developed proteinuria ≥[1+]. Participants in the borderline diabetes group did not have a significantly higher risk of eGFR <60 ml/min/1.73 m2 or proteinuria ≥[1+] after multivariable adjustment. However, participants with borderline diabetes who were also diagnosed with borderline diabetes at the endpoint examination had a significantly higher risk of proteinuria ≥[1+] compared with participants with normoglycemia who also had normoglycemia at the endpoint examination; the HR (95 % CI) was 1.76 (1.11-2.78). CONCLUSIONS: Persistent borderline diabetes significantly increases the risk of proteinuria.

Association between smoking and post-load plasma glucose levels using a 75-g oral glucose tolerance test: the Saku Study.

Current smoking was associated with low insulin secretion and high 30-min plasma glucose (PG), 60-min PG, and area under the curve of PG, whereas current smoking was not associated with fasting PG and 2-h PG levels in both individuals with normoglycemia and individuals with pre-diabetes in a large-scale community-based study.

Impact of cigarette smoking on impaired insulin secretion and insulin resistance in Japanese men: The Saku Study.

AIMS/INTRODUCTION: To assess the impact of smoking on impaired insulin secretion and insulin resistance in Japanese men. MATERIALS AND METHODS: This study included 1,199 men aged 30-79 years without diabetes, impaired insulin secretion and insulin resistance at baseline who underwent a comprehensive medical check-up between April 2006 and March 2007 at Saku Central Hospital. Smoking status was categorized as current, ex-smoker and never-smoker. Insulinogenic index and homeostasis model assessment-insulin resistance were determined using a standard 75-g oral glucose tolerance test. The Japan Diabetes Society criteria were used to define impaired insulin secretion and insulin resistance. Participants were followed up until March 2011. RESULTS: A total of 449 and 99 men developed impaired insulin secretion and insulin resistance during 3,403 and 4,092 person-years follow up, respectively. The multivariable-adjusted hazard ratios (HRs) for impaired insulin secretion were 1.06 (95% confidence interval [CI] 0.84-1.33) in ex-smokers and 1.95 (95% CI 1.44-2.63) in current smokers compared with never-smokers after adjustment for age, familial history of diabetes, alcohol consumption, exercise, systolic blood pressure, triglyceride, γ-glutamyltransferase, waist circumference, leukocyte count, changes in smoking status and changes in waist circumference. The number of pack-years was positively associated with the risk for impaired insulin secretion in a dose-dependent manner (P-values for trend <0.001). The multivariable-adjusted HRs for insulin resistance were 0.95 (95% CI 0.56-1.61) in ex-smokers and 1.11 (95% CI 0.67-1.79) in current smokers compared with never-smokers. CONCLUSIONS: Cigarette smoking is a modifiable risk factor for impaired insulin secretion. The findings might also be important for other Asian populations, which have low insulin secreting ability.

Effects of healthy dietary pattern and other lifestyle factors on incidence of diabetes in a rural Japanese population.

This study assessed the effects of dietary habits and other lifestyle factors on the incidence of diabetes in a rural Japanese population. This 10.3-year study investigated a cohort of 1,995 men and 3,670 women aged 40-69 years without diabetes at baseline who underwent health check-ups between April 1990 and March 1992. Participants were followed up until diabetes was confirmed or until the end of 2006. The incidence of diabetes was determined from fasting and random levels of plasma glucose, HbA1c levels or being under medical treatment for diabetes. Principal component analysis identified a major dietary pattern characterized by more frequent consumption of vegetables, potatoes, seaweeds, fruits and soybean products that we labeled "healthy". Diabetes developed in 446 of the participants during 58,151 person-years of follow-up. Consuming a healthy diet was associated with a lower risk of diabetes (multivariable-adjusted hazard ratio for highest vs lowest quartiles, 0.78 [95% CI, 0.61- 0.95]. In addition, scores for a healthy diet were associated with a lower risk for diabetes among persons who consumed regular meals (0.76 [0.58-0.96]), persons with an exercise habit (0.65 [0.44-0.96]) and non- and ex-smokers (0.72 [0.53-0.96]). Our findings suggest that consuming a healthy diet is associated with a lower risk for diabetes among the Japanese, particularly among those who eat regularly, those who habitually exercise and non- and ex-smokers.

Impact of smoking cessation on incidence of diabetes mellitus among overweight or normal-weight Japanese men.

AIMS: To assess the impact of smoking cessation on incidence of diabetes among overweight or normal-weight Japanese men. METHODS: This 9.2-year cohort study included 2070 men aged 40-69 years without diabetes. We classified them according to smoking status as non-smokers, past smokers (>9, 6-9, 3-5 and <3 years) and current smokers. Participants were followed up until diabetes developed or the end of 2006. The incidence of diabetes was determined from fasting and random plasma glucose levels, HbA(1c) levels or being under medical treatment for diabetes. RESULTS: During 18,963 person-years of follow-up, 246 of the participants developed diabetes. The risk for diabetes peaked within 3 years of quitting (HR: 2.98, 95% CI: 1.38-6.27) and persisted at 5 years after quitting smoking (HR, 2.49; 95% CI, 1.18-5.26) among overweight individuals. Moreover, this study identified a high risk for diabetes among past smokers who had quit >9 years in both normal weight and overweight. CONCLUSIONS: Cigarette smoking predicts incidence of diabetes, but smoking cessation leads to higher short-term risk in overweight and long-term risk in both. Preventing smoking is superior to smoking cessation, and is very important for avoiding diabetes.

Risk of smoking and body mass index for incidence of diabetes mellitus in a rural Japanese population.

OBJECTIVE: To assess the risk of smoking, body mass index (BMI), and both for incidence of diabetes in a rural Japanese population. METHOD: This study was a 10.1-year cohort study of 2070 men and 3802 women aged 40-69 years without diabetes at baseline who underwent a health check-up at one central hospital in Nagano Prefecture. Participants were classified according to a combination of smoking status and BMI. Participants were followed from 1990 to 2006. The incidence of diabetes was determined from fasting and random levels of plasma glucose, HbA(1c) levels or being under medical treatment for diabetes. RESULTS: Diabetes developed in 595 of the participants during 59,111 person-years of follow-up. In men, the multivariable-adjusted hazard ratios for incidence of diabetes compared with non-smokers of normal weight were as follows: 3.36 (2.02-5.60) in current smokers with normal weight and 1.70 (0.87-3.34) and 3.93 (2.22-6.96) in obese non-smokers and obese current smokers, respectively. In men the population-attributable fraction of diabetes onset due to current smoking, obesity and both were 22.0%, 2.5% and 11.2%, respectively. CONCLUSION: Regardless of BMI, smoking is an important risk factor for diabetes in male populations with a high prevalence of smoking.