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Aims: Visceral adiposity measured by computed tomography (CT) as intra-abdominal fat area (IAFA) predicts metabolic diseases. Existing adiposity surrogates have not been systematically compared to a regression-based model derived in individuals of Japanese ancestry. We developed and validated a method to estimate IAFA in individuals of Japanese ancestry and compared it to existing adiposity surrogates.Methods: We assessed age, BMI, waist circumference (WC), fasting lipids, glucose, smoking status, grip strength, mid-thigh circumference (MTC), humeral length, leg length, and IAFA by single-slice CT at the umbilicus for 622 Japanese Americans. We used stepwise linear regression to predict IAFA and termed the predicted value the Estimate of Visceral Adipose Tissue Area (EVA). For men, the final model included age, BMI, WC, high-density lipoprotein cholesterol (HDLc), glucose, and MTC; for women, age, BMI, WC, HDLc, low-density lipoprotein cholesterol, glucose, and MTC. We compared goodness-of-fit (R2) from linear regression models and mean-squared errors (MSE) from k-fold cross-validation to compare the ability of EVA to estimate IAFA compared to an estimate by Després et al., waist-to-height ratio, WC, deep abdominal adipose tissue index, BMI, lipid accumulation product, and visceral adiposity index (VAI). We classified low/high IAFA using area under receiver-operating characteristic curves (AUROC) for IAFA dichotomized at the 75th percentile.Results: EVA gave the least MSE and greatest R2 (men: 1244, 0.61; women: 581, 0.72). VAI gave the greatest MSE and smallest R2 (mean 2888, 0.08; women 1734, 0.14).Conclusions: EVA better predicts IAFA in Japanese-American men and women compared to existing surrogates for adiposity. [ABSTRACT FROM AUTHOR]

Aim: The prevalence of underweight women, who have an increased risk for small-for-gestational-age (SGA) birth, is increasing in Japan. We examined the associations of pre-pregnancy body mass index and gestational weight gain (GWG) with SGA birth among Japanese women. Material and Methods: We conducted a prospective cohort study of 1391 women who delivered full-term singleton babies. SGA was defined as below the 10th percentile of birthweight at each gestational age, baby sex, and parity. We calculated the 5th percentile of birthweight in the same way for another threshold for SGA. According to pre-pregnancy body mass index, we divided the participants into three groups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), and overweight and obese (≥25.0 kg/m2). Results: SGA birth was observed most frequently among the underweight group (13.8%). Underweight was associated with an increased risk of SGA birth. The multiple-adjusted odds ratio for underweight was 1.96 (95% confidence interval, 1.23-3.11) compared with normal weight. Sufficient GWG reduced the incidence and the multiple-adjusted odds ratio for 1-kg increase of GWG was 0.86 (0.81-0.92). The same tendency was observed for the delivery of infants below the 5th birthweight percentile. Women with underweight and normal weight who had 9.0 kg or less of GWG had a significantly higher risk of SGA birth than women with normal weight who had 9.1-11.0 kg of GWG. Conclusions: Underweight and poor GWG were associated with a higher incidence of SGA birth. However, the incidence of SGA birth among underweight women was not increased significantly if they had sufficient GWG. [ABSTRACT FROM AUTHOR]

Background Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed. Methods Study participants included 10 631 Japanese men aged 40e55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was $7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires. Results During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4e7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1e2.0 or 2.1e4.0 US standard drinks per drinking day on 4e7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers. Conclusions More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4e7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers. [ABSTRACT FROM AUTHOR]

Investigates the association of the duration of the walk to work and leisure-time physical activity with the risk for hypertension. Decrease in risk for hypertension in Japanese men engaged in walking to work and other types of physical activity; Importance of regular exercise.

OBJECTIVE -- We prospectively assessed whether the combined measurements of fasting plasma glucose (FPG) and A1C were effective for predicting type 2 diabetes. RESEARCH DESIGN AND METHODS-- Study participants included 6,736 nondiabetic Japanese men aged 40-55 years. Type 2 diabetes was diagnosed in those who had an FPG ≥126 mg/dl or who were being treated with an oral antidiabetic agent or insulin. The models including FPG, A1C, and both were compared using the area under the receiver operating characteristic (AUROC) curves. RESULTS -- During the 4-year follow-up period, we confirmed 659 diabetes cases. In multivariate analysis, both FPG and A1C were independently associated with the risk of type 2 diabetes. The model including both FPG and A1C had a greater AUROC curve than that including FPG alone (0.853 vs. 0.818; P < 0.001) or A1C alone (0.853 vs. 0.771; P < 0.001). CONCLUSIONS -- The combined measurement of FPG and A1C was effective for predicting type 2 diabetes. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relationship between walking to work and the development of type 2 diabetes in Japanese men. It mentions that studies revealed that physical activity is effective in preventing diabetes. Men were examined based on their leisure-time physical activity, smoking habits and alcohol intake. The result of the study provided evidence that duration of the walk going to work has an independent effect on the risk of type 2 diabetes.

Background: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals., Methods: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m 2 , which was the upper 2.5th percentile value of eGFR in the entire cohort., Results: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively., Conclusion: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.

Background: Serum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR)., Methods: We prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m 2 ., Results: During the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR., Conclusion: In middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

Objectives: We conducted a retrospective cohort study to examine the risk of bile duct cancer among current and former workers in the offset color proof printing department at a printing company in Osaka, Japan., Methods: Standardized incidence ratios (SIRs) between January 1, 1985, and December 31, 2012, were estimated for the cumulative years of exposure to two chemicals, dichloromethane (DCM) and 1,2-dichloropropane (1,2-DCP), using the national incidence level as a reference. In addition, we examined risk patterns by the calendar year in which observation started., Results: Among 106 workers with a total of 1,452.4 person-years of exposure, 17 bile duct cancer cases were observed, resulting in an estimated overall SIR of 1,132.5 (95% confidence interval (CI): 659.7-1,813.2). The SIR was 1,319.9 (95% CI: 658.9-2,361.7) for those who were exposed to both DCM and 1,2-DCP, and it was 1,002.8 (95% CI: 368.0-2,182.8) for those exposed to 1,2-DCP only. SIRs tended to increase according to years of exposure to 1,2-DCP but not DCM when a 5-year lag time was assumed. The SIRs were higher for the cohorts in which observation started in 1993-2000, particularly in cohorts in which it started in 1996-1999, compared with those in which it started before or after 1993-2000., Conclusions: We observed an extraordinarily high risk of bile duct cancer among the offset color proof printing workers. Elevated risk may be related to cumulative exposure to 1,2-DCP, but there remains some possibility that a portion of the risk is due to other unidentified substances.

Background: Although short sleep duration has been reported to be associated with future cardiometabolic diseases, it is not fully understood whether sleep duration is prospectively associated with the risk of each lipid profile abnormality., Methods: Subjects were nondiabetic Japanese, 40-55 years of age, who were not taking oral lipid-lowering medications: for the incidence of low high-density lipoprotein cholesterol (HDL-C), 7627 men with an HDL-C level ≥ 40 mg/dL; for high triglycerides, 6973 men with a triglyceride level <200 mg/dL; for high low-density lipoprotein cholesterol (LDL-C), 7273 men with an LDL-C level <160 mg/dL; for high non-HDL-C, 7415 men with a non-HDL-C level <190 mg/dL; and for high total cholesterol (TC), 7196 men with a TC level <240 mg/dL. Lipid profile abnormalities were defined according to the Adult Treatment Panel III guidelines of the National Cholesterol Education Program., Results: During the 6-year observation period, there were 1022 cases of low HDL-C. Multiple-adjusted hazard ratios for low HDL-C were 0.79 (95% confidence interval, 0.64-0.97) for sleep durations of 5 to <7 h and 0.62 (0.46-0.83) for ≥ 7 h compared with <5 h. There were 1473 cases of high triglycerides. Multiple-adjusted hazard ratios for high triglycerides were 0.81 (0.68-0.98) for sleep durations of 5 to <7 h and 0.90 (0.72-1.13) for ≥ 7 h compared with <5 h. However, no association between sleep duration and the risk of future high LDL-C, non-HDL-C, or TC was observed., Conclusions: Moderate and/or long sleep durations decreased the risk of future low HDL-C and high triglycerides., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma., Methods: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young., Results: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available., Conclusions: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Objectives: An outbreak of neurological health disorder caused by drinking well water occurred in 2003 at one apartment building in Kamisu, Ibaraki, Japan. This was the first case of mass poisoning due to well water contaminated with diphenylarsinic acid (DPAA). Subsequently, other residents in Kamisu were confirmed to have drunk well water containing lower concentrations of DPAA. The present study aimed to investigate neurological and other subjective symptoms and miscarriage occurrences after DPAA exposure., Methods: Subjects were residents of Kamisu aged 10-65 years in 2004. Twenty residents (high-level exposure group) had lived in the apartment building and drunk well water containing DPAA at arsenic concentrations of 2,262 μg/L. The moderate/low-level exposure group (67 residents) had drunk other well water containing DPAA at arsenic concentrations of 2-230 μg/L (mean: 85 μg/L) and DPAA was detected in their hair or nails. A control group (134 residents), matched to the latter group by sex and age, had only drunk tap water. Public health nurses completed a questionnaire on symptoms, pregnancy, and miscarriage through interviews., Results: Dizziness, unsteadiness, dysesthesia, writing disturbance, diplopia, insomnia, melancholy, headache, itchiness, weight change, diarrhea, cough, and dyspnea were significantly higher in the moderate/low-level exposure group than in the control group. A similar tendency was found in the high-level exposure group. From 1999 through 2003, no miscarriages occurred among 15 pregnancies in the control group, while three miscarriages occurred among five pregnancies in the moderate/low-level group., Conclusion: DPAA exposure via well water caused miscarriage, in addition to neurological and other subjective symptoms.

Background/aims: The association between alcohol consumption and the risk of chronic kidney disease (CKD) has been reported. What is not known is whether drinking pattern combined with the weekly frequency of alcohol consumption and the quantity per drinking day is associated with the risk of CKD., Methods: We enrolled 9,112 Japanese nondiabetic men aged 40 to 55 years with absence of proteinuria, an estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73 m(2) or higher, and not on antihypertensive medications at baseline. CKD was defined if eGFR was <60 ml/min/1.73 m(2). The weekly frequency classification was nondrinkers, 1-3 drinking days/week, or 4-7 drinking days/week. The quantity consumed per drinking day was classified as 0.1-23.0 g ethanol/drinking day, 23.1-46.0 g ethanol/drinking day, 46.1-69.0 g ethanol/drinking day, and ≥69.1 g ethanol/drinking day., Results: During the 79,099 person-years, 1,253 subjects developed CKD. Compared to nondrinkers, those who consumed 23.1-46.0 or 46.1-69.0 g ethanol/drinking day on 4-7 drinking days/week had a decreased risk of CKD (multiple-adjusted hazard ratio (HR) 0.62 (0.52-0.74) and 0.76 (0.59-0.97), respectively). The association between the quantity per drinking day and the incidence of CKD was U-shaped among each category of the weekly frequency. HRs within similar categories of quantity per drinking day were lower in the 4-7 drinking days/week group than in the 1-3 drinking days/week group., Conclusion: Among middle-aged Japanese men, the people who drank middle-range quantity, specifically who drank 4-7 days/week, had lower risk of CKD than nondrinkers., (© 2014 S. Karger AG, Basel.)

Background: Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population., Methods: This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls., Results: The median (inter-quartile range) DHEA-S levels were 771 (447-1351) and 414 (280-659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40-53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients., Conclusions: The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes.

Background: Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes. However, the relationship between drinking patterns, such as the weekly frequency of alcohol consumption and the quantity per drinking day, and the incidence of type 2 diabetes has not been sufficiently addressed., Methods: Study participants included 10 631 Japanese men aged 40-55 years without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was ≥7.0 mmol/l or if participants were taking diabetes medications. Data on alcohol consumption were obtained from questionnaires., Results: During the 37 172 person-years of follow-up, we confirmed 878 cases of type 2 diabetes. Frequent alcohol consumption was associated with a low risk of type 2 diabetes. Compared to non-drinkers, the multiple-adjusted HR for those who drank 4-7 days weekly was 0.76 (95% CI, 0.63 to 0.92). To assess the association between drinking pattern and type 2 diabetes, we examined the joint association of the weekly frequency and the quantity per drinking day with type 2 diabetes. Men who consumed 0.1-2.0 or 2.1-4.0 US standard drinks per drinking day on 4-7 days weekly had a lower risk of type 2 diabetes (HR 0.74, 95% CI 0.58 to 0.95; HR 0.74, 95% CI 0.60 to 0.91, respectively) compared to non-drinkers., Conclusions: More frequent alcohol consumption lowered the risk of type 2 diabetes. Light to moderate alcohol consumption per drinking day on 4-7 days weekly lowered the risk of type 2 diabetes compared to non-drinkers.

Background and Objectives: Glomerular hyperfiltration and albuminuria accompanied by early-stage diabetic kidney disease predict future renal failure. Cigarette smoking has reported to be associated with elevated GFR in cross-sectional studies and with renal deterioration in longitudinal studies. The degree of glomerular hyperfiltration and proteinuria associated with smoking, which presumably is a phenomenon of early renal damage, has not been investigated in a satisfying manner so far., Design, Setting, Participants, & Measurements: This study included 10,118 Japanese men aged 40 to 55 years without proteinuria or renal dysfunction at entry. Estimated GFR was calculated using the Modification of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was defined as estimated GFR ≥117.0 ml/min per 1.73 m(2), which was the upper 2.5th percentile value of estimated GFR in the total population. Proteinuria was detected using standard dipstick., Results: During the 6-year observation period, there were 449 incident cases of glomerular hyperfiltration and 1653 cases of proteinuria. Current smokers had a 1.32-time higher risk for the development of glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than nonsmokers after adjustment for baseline age, body mass index, systolic and diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular leisure-time physical activity, and estimated GFR. Both daily and cumulative cigarette consumption were associated with an increased risk for glomerular hyperfiltration and proteinuria in a dose-response manner., Conclusions: In middle-aged Japanese men, smoking was associated with an increased risk of glomerular hyperfiltration and dipstick proteinuria. Of importance, past smokers did not exhibit any increased risk for these conditions.

Visceral adiposity is considered to have a key role in cardiometabolic diseases. The purpose of this study is to investigate cross-sectionally the association between intra-abdominal fat area (IAFA) measured by computed tomography (CT) and high blood pressure independent of abdominal subcutaneous fat area (ASFA) and insulin resistance. Study participants included 624 Japanese men not taking oral hypoglycemic medications or insulin. Abdominal, thoracic and thigh fat areas were measured by CT. Total fat area (TFA) was calculated as the sum of abdominal, thoracic and thigh fat area. Total subcutaneous fat area (TSFA) was defined as TFA minus IAFA. Hypertension and high normal blood pressure were defined using the 1999 criteria of the World Health Organization. Multiple-adjusted odds ratios of hypertension for tertiles of IAFA were 2.64 (95% confidence interval, 1.35-5.16) for tertile 2, and 5.08 (2.48-10.39) for tertile 3, compared with tertile 1 after adjusting for age, fasting immunoreactive insulin, diabetes status, ASFA, alcohol consumption, regular physical exercise and smoking habit. IAFA remained significantly associated with hypertension even after adjustment for ASFA, TSFA, TFA, body mass index or waist circumference, and no other measure of regional or total adiposity was associated with the odds of hypertension in models, which included IAFA. Similar results were obtained for the association between IAFA and the prevalence of high normal blood pressure or hypertension. In conclusion, greater visceral adiposity was associated with a higher odds of high blood pressure in Japanese men.

It is unclear which blood pressure (BP) components (that is, systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP) and mean arterial pressure (MAP)) are superior predictors of chronic kidney disease (CKD). Furthermore it is unclear whether the combination of SBP+DBP or PP+MAP is superior to any of these four individual BP components in predicting CKD. We enrolled 9928 Japanese men aged 40-55 years who had a normal estimated glomerular filtration rate (eGFR), no proteinuria and no history of cardiovascular disease and were not taking any antihypertensive medications at baseline. CKD was defined as an eGFR of <60 ml min(-1) per 1.73 m(2) using the modified diet in renal disease equation. ΔAkaike's information criterion (ΔAIC) was used to compare the BP components-added model to the model without them in a Cox proportional hazards model. During the 52 428 person-years of follow-up, there were 434 cases of CKD. Of all four BP components, the model including DBP- or MAP-alone had the highest values of ΔAIC (10.2 and 9.85, respectively). The PP-alone model had the lowest ΔAIC value (-1.48). The combination models including SBP+DBP (ΔAIC 8.42) or PP+MAP (8.42) were not superior to the models including DBP- or MAP-alone. These findings suggested that, of the four BP components, both DBP and MAP were the most useful predictors for subsequent incidence of CKD, but PP was not an important predictor. The combination model, including SBP+DBP or PP+MAP, was not superior to the models including DBP- or MAP-alone for predicting CKD.

Background/aims: No prospective studies have estimated the association between white blood cell (WBC) count and the risk of proteinuria. We prospectively examined the relationships of WBC count, as a marker of inflammation, with two outcomes: proteinuria and low estimated glomerular filtration rate (eGFR)., Methods: We enrolled 10,008 Japanese men aged 40-55 years who had neither proteinuria nor low eGFR and were not taking antihypertensive medications at entry. Proteinuria was defined as 1+ or higher on urine dipstick. Low eGFR was defined if eGFR was <60 ml/min/1.73 m(2)., Results: During the 49,644 person-years of follow-up, 1,557 cases of proteinuria were confirmed. After adjusting for age, body mass index, fasting plasma glucose, systolic blood pressure, diastolic blood pressure, antidiabetic medications, alcohol consumption, smoking, regular leisure-time physical activity and eGFR, the highest quintile (≥7.51 × 10(3)/μl) of WBC count was independently associated with an increased risk of incidence of proteinuria [HR: 1.45 (95% CI: 1.23-1.73)] compared with the lowest quintile (≤4.80 × 10(3)/μl). On the other hand, during 52,833 person-years, we confirmed 439 cases of low eGFR. In multivariate models, there was no association between WBC count and low eGFR., Conclusion: Elevated WBC count was independently associated with an increased risk of proteinuria, but not low eGFR., (Copyright © 2011 S. Karger AG, Basel.)

Objective: It has been reported that moderate alcohol consumption decreased the risk of type 2 diabetes but that elevated liver enzymes increased it. The comparative importance of alcohol consumption and liver enzymes as predictors of type 2 diabetes remains unconfirmed., Research Design and Methods: The participants included 8,576 Japanese men, aged 40-55 years, without type 2 diabetes at entry. Type 2 diabetes was diagnosed if a fasting plasma glucose level was >or=126 mg/dl or if participants were taking oral hypoglycemic medications or insulin., Results: During the 4-year follow-up period, we confirmed 878 cases. In multivariate models, moderate daily alcohol consumption (16.4-42.6 g ethanol/day) decreased the risk of type 2 diabetes, and higher levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) increased the risk. In joint analyses of alcohol consumption and liver enzymes, moderate drinkers with the lowest tertile of GGT had the lowest risk of type 2 diabetes. Compared with them, nondrinkers with the highest GGT had the highest risk of type 2 diabetes (odds ratio 3.18 [95% CI 1.75-5.76]). At every level of GGT, moderate or heavy alcohol drinkers (>or=42.7 g ethanol/day) had a lower risk of type 2 diabetes than nondrinkers. The relationship of ALT and daily alcohol consumption with the risk of type 2 diabetes was almost the same as that of GGT., Conclusions: GGT, ALT, and daily alcohol consumption were independently associated with the risk of type 2 diabetes. Nondrinkers with the highest GGT or ALT had a high risk of type 2 diabetes.

Objective: Visceral adiposity is generally considered to play a key role in the metabolic syndrome. We sought to determine whether greater visceral adiposity directly measured by computed tomography (CT) is associated with increased future insulin resistance independent of other adipose depots., Research Design and Methods: We followed 306 nondiabetic Japanese Americans over 10-11 years. Baseline variables included BMI; waist circumference; and abdominal, thoracic, and thigh fat areas measured by CT. Total fat area was estimated by the sum of all of these fat areas. Visceral adiposity was measured as intra-abdominal fat area at the umbilicus level. Total subcutaneous fat area was defined as total fat area minus intra-abdominal fat area. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), fasting plasma insulin level, Matsuda index, and area under the oral glucose tolerance test curve (AUC) of insulin., Results: Both baseline intra-abdominal fat area (P = 0.002) and HOMA-IR (P < 0.001) were independently associated with increased HOMA-IR at 10-11 years in a multiple linear regression model after adjustment for abdominal subcutaneous fat area, age, sex, 2-h plasma glucose level, and incremental insulin response. Intra-abdominal fat area remained a significant predictor of increased HOMA-IR at 10-11 years even after adjustment for total subcutaneous fat area, total fat area, BMI, or waist circumference, but no other measure of CT-measured regional or total adiposity was significantly related with HOMA-IR at 10-11 years in models that contained intra-abdominal fat area. Similar results were obtained for predicting future fasting plasma insulin level, Matsuda index, and AUC of insulin., Conclusions: Greater visceral adiposity is associated with an increase in future insulin resistance.

Objective: Japanese American is an ethnic group with a high risk for type 2 diabetes, which is linked to the metabolic syndrome. Central adiposity is considered to play a key role in the metabolic syndrome. Not known are the optimal cut point values for central and visceral adiposity to identify Japanese Americans at risk for the metabolic syndrome., Research Design and Methods: Study subjects included 639 Japanese Americans. The nonadipose variables of the metabolic syndrome were defined using modified International Diabetes Federation criteria, and the accuracy of identifying at least two of these by intra-abdominal fat area (IAFA) as measured by computed tomography and waist circumference was cross-sectionally assessed using area under receiver operating characteristic (ROC) curves. The values for IAFA and waist circumference that resulted in maximizing the Youden index were defined as "optimal.", Results: The area under the ROC curve for IAFA exceeded that for waist circumference (men 0.787 vs. 0.686; women 0.792 vs. 0.721). For women, the optimal cut points for IAFA and waist circumference were 51.5 cm(2) and 80.8 cm (age < or = 56 years) and 86.3 cm(2) and 89.0 cm (age > 56 years). For men, the optimal cut points for IAFA and waist circumference were 88.6 cm(2) and 90.0 cm (age < or = 57 years) and 96.1 cm(2) and 87.1 cm (age > 57 years)., Conclusions: These results argue that current Japanese waist circumference cut points for the metabolic syndrome need to be revised. Moreover, the waist circumference and IAFA cut points should be age specific, especially in women. Appropriate waist circumference cut points are from 80 to 90 cm in women and from 87 to 90 cm in men.

Background: The reflection waveform in the ascending aortic pressure has been reported to reflect systemic arterial stiffness, and increase risk of coronary heart disease. The purpose of this study is to evaluate prospectively whether the reflection waveform in the ascending aortic pressure is associated with the mortality in patients with chronic renal failure on hemodialysis., Methods: Fifty two patients with chronic renal failure on hemodialysis and undergoing cardiac catheterizations were enrolled in this study. Inflection time was measured to determine the reflection waveform in the ascending aortic pressure at angiography. Inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point., Results: The mean duration of follow-up was 55 +/- 49 months (mean +/- SD). Mean age at entry was 58.5 +/- 9.0 years. We confirmed 14 cardiovascular deaths, and 5 non-cardiovascular deaths. Shorter inflection time increased all-cause and cardiovascular mortality. Kaplan-Meier analysis demonstrated a significantly reduced survival ratio in patients with inflection time < or =87 msec (all-cause death; P < 0.01, cardiovascular death; P < 0.001 by log-rank test). Multiple-adjusted hazard ratio for 10 msec decrease in inflection time was 1.49 (95% confidence interval, 1.07 to 2.08) for all-cause mortality, and was 4.66 (95% confidence interval, 1.82 to 11.95) for cardiovascular mortality., Conclusion: Shorter inflection time increased all-cause and cardiovascular mortality in patients with chronic renal failure on hemodialysis.

Background: Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin., Methods and Results: Study subjects included 563 Japanese Americans with normal or impaired glucose tolerance or diabetes but not taking oral hypoglycemic medication or insulin at entry. Variables included plasma glucose and insulin measured after an overnight fast and during an oral glucose tolerance test, and abdominal, thoracic, and thigh fat areas by CT. Total fat area (TFA) was calculated as the sum of these fat areas. Hypertension was defined as having a systolic blood pressure > or =140 mm Hg, having a diastolic blood pressure > or =90 mm Hg, or taking antihypertensive medications. Intra-abdominal fat area (IAFA) was associated with a higher prevalence of hypertension. Adjusted odds ratio of hypertension by IAFA was 1.68 for a 1-SD increase (95% CI, 1.20 to 2.37) after adjusting for age, sex, fasting plasma insulin, a nonlinear transformation of 2-hour plasma glucose, and TFA. IAFA remained a significant predictor of prevalence of hypertension even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, body mass index, or waist circumference, but no measure of regional or total adiposity was associated with the odds of prevalence of hypertension in models that contained IAFA., Conclusions: Greater visceral adiposity increases the odds of hypertension in Japanese Americans independent of other adipose depots and fasting plasma insulin.

Objective: Greater visceral adiposity, higher insulin resistance, and impaired insulin secretion increase the risk of type 2 diabetes. Whether visceral adiposity increases risk of impaired glucose tolerance (IGT) independent of other adipose depots, insulin resistance, and insulin secretion is not known., Research Design and Methods: Study subjects included 128 Japanese Americans with normal glucose tolerance at entry. Baseline variables included plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, fat areas by computed tomography, insulin secretion (incremental insulin response [IIR] [30 min insulin - fasting insulin]/30 min glucose), and insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR])., Results: During the 10- to 11-year follow-up period, we confirmed 57 cases of IGT. Significant predictors of IGT included intra-abdominal fat area (IAFA) (odds ratio [OR] for a 1 SD increase 3.82, 95% CI 1.63-8.94 at a fasting plasma glucose [FPG] level of 4.5 mmol/l), HOMA-IR (2.41, 1.15-5.04), IIR (0.30, 0.13-0.69 at an FPG level of 4.5 mmol/l), the interactions of IAFA by FPG (P = 0.003), and IIR by FPG (P = 0.030) after adjusting for age, sex, FPG, and BMI. The multiple-adjusted OR of IAFA increased and that of IIR decreased as FPG level decreased because of these interactions. Even after adjustment for total fat area, total subcutaneous fat area, or abdominal subcutaneous fat area, all of these associations remained a significant predictor of IGT incidence., Conclusions: Greater visceral adiposity increases the risk of IGT independent of insulin resistance, insulin secretion, and other adipose depots in Japanese Americans.

Objective: To investigate the relationship between blood pressure at 4 min after exercise using a Master's two-step and the risk for hypertension., Design: Prospective cohort study., Setting: Work site in Osaka, Japan., Participants: A total of 6557 Japanese men, aged 35-63 years with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, and no history of hypertension or diabetes at baseline., Main Outcome Measures: Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Normotension was defined as no history of hypertension, and SBP < 130 mmHg and DBP < 85 mmHg. High normal blood pressure was defined as no history of hypertension and SBP >or= 130 and < 140 mmHg or DBP >or= 85 and < 90 mmHg., Results: During the 63 696 person-years follow-up period, we confirmed 660 cases of hypertension. SBP and DBP after exercise were associated with an increased risk for developing hypertension. The multiple-adjusted relative risk for SBP and DBP after exercise were 1.55 per 10 mmHg (confidence interval, 1.42-1.69) and 1.55 per 10 mmHg (confidence interval, 1.42-1.69), respectively. These associations were independent of resting SBP and DBP. Even after stratifying subjects according to blood pressure at rest, SBP or DBP at 4 min after exercise was associated with an increased risk for hypertension in subjects with normotension or high normal blood pressure at rest., Conclusions: The blood pressure response after exercise with a two-step was associated with an increased risk for hypertension, independently of resting blood pressures.