Ginji Endo

Serum uric acid and the risk for hypertension and Type 2 diabetes in Japanese men: The Osaka Health Survey

Objective To investigate the association of serum uric acid level with the risk for hypertension and Type 2 diabetes. Design Prospective cohort study. Setting Work site in Osaka, Japan. Participants A total of 6356 Japanese men, aged 35–60 years with systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, normal glucose intolerance, 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. Type 2 diabetes was defined as a fasting plasma glucose level ⩾ 126 mg/dl or a 2 h post–loaded plasma glucose level ⩾ 200 mg/dl. Results During the 61 716 person–years follow-up period, we confirmed 639 cases of hypertension and 454 cases of Type 2 diabetes. Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes. After adjustment for known risk factors, including daily alcohol consumption, the serum uric acid level was associated with an increased risk for hypertension; the relative risks for hypertension were 1.00 for quintile 1 of the serum uric acid level, 1.24 [95% confidence interval (CI), 0.94–1.65] for quintile 2, 1.34 (CI, 1.03–1.76) for quintile 3, 1.76 (CI, 1.35–2.29) for quintile 4, and 2.01 (CI, 1.56–2.60) for quintile 5 (P for trend < 0.001). Even among both non-drinkers and lean subjects, serum uric acid level was associated with an increased risk for hypertension. Conclusions Serum uric acid level was associated with an increased risk for hypertension but not for Type 2 diabetes.

Walking to work and the risk for hypertension in men : The Osaka Health Survey

There is good evidence that physical activity reduces the risk for cardiovascular disease (1-6), possibly in part by lowering blood pressure (7). Although mild or moderate physical activity, such as brisk walking, is a recommended part of the treatment protocol for persons with hypertension (8, 9), it is not known whether mild physical activity, especially walking, reduces the risk for hypertension. With few exceptions, epidemiologic studies of physical activity and hypertension have been cross-sectional rather than prospective. Physical activity was inversely related to blood pressure in cross-sectional and controlled studies (7), and in two prospective studies (10, 11), vigorous exercise was inversely related to the subsequent risk for hypertension. Physicians in Japan usually advise their patients to walk to work as often as they can, and indeed, for middle-aged working Japanese men, the journey to and from work seems to be the main source of exercise. We prospectively examined the relation of mild physical activity, especially walking to work, and leisure-time physical activity to the risk for hypertension during 6 to 16 years of observation. Methods The Osaka Health Survey The Osaka Health Survey is an ongoing cohort study of risk factors for chronic diseases, including hypertension and diabetes. Study participants are male employees of a gas company in Osaka, Japan. Japanese law requires all employers to conduct annual health screenings for all employees. For the purposes of the Osaka Health Survey, in addition to these annual screenings, all employees 35 years of age or older undergo more detailed biennial clinical examinations and complete questionnaires on health-related behaviors, including exercise. Study Sample Between 1981 and 1990, 7979 Japanese men 35 to 63 years of age at entry who had sedentary occupations were enrolled in the study. We excluded 1875 men because they had physician-diagnosed hypertension, borderline hypertension (systolic blood pressure 140 and<160 mm Hg, diastolic blood pressure 90 and<95 mm Hg, or both in men without a history of hypertension), diabetes, or impaired glucose tolerance (fasting plasma glucose level 6.1 mmol/L [ 110 mg/dL] and<7.8 mmol/L [<140 mg/dL] in men with no history of diabetes) at entry. The study sample ultimately consisted of 6104 men. Data Collection and Measurements The biennial clinical examination consisted of a medical history; a physical examination; blood pressure measurement; anthropometric measurements; measurement of the fasting plasma glucose level; and surveys of health-related behaviors, such as physical activity, smoking, and daily alcohol consumption. Trained nurses took all measurements. Participants were asked to fast for 12 hours and to avoid smoking and heavy physical activity for more than 2 hours before the examination. After a 5-minute rest in a quiet room, a standard mercury sphygmomanometer was used to measure systolic and diastolic blood pressures in the right arm while the participant was seated. Pressure was measured twice, at an interval of a few minutes. Anthropometric measurements included height and body weight, which were measured while the participant was wearing light clothing without shoes. Body mass index was calculated as the weight in kilograms divided by the height in meters squared. The questionnaire completed by each participant elicited information on leisure-time physical activity, the duration of the walk to work, the nature of the participants occupation, and the level of activity involved. Leisure-time physical activity was defined as physical activity unrelated to the participants work. Questions about leisure-time physical activity were as follows: Do you engage in any regular physical exercise, such as jogging, bicycling, swimming, and tennis, long enough to work up a sweat (lasting 30 minutes or more)? If yes, how many times per week? What exercise is this? The questions about regular physical exercise have been validated as a measure of physical exercise (12-15). In the analysis, participants were classified as engaging in regular physical exercise at least once per week or less than once per week. They were also classified into one of three categories of exercise frequency: 0 (less than once per week), once per week, or two or more times per week. The question about the duration of the walk to work was How long does it take you to walk to this office? Occupational activity was scored as 1 if the participants work was mostly sedentary and 2 if he worked outside or if the job required a lot of lifting and walking. In the present study, we excluded all participants who reported a score of 2 for their occupational activities. Questions about alcohol intake included items about the type of alcoholic beverage, the weekly frequency of alcohol consumption, and the usual amount consumed daily. Alcohol intake was converted to total alcohol consumption (in milliliters of ethanol per day) by using standard Japanese tables. Current and past smoking habits were classified according to the type and quantity of cigarettes smoked daily. Participants were classified as current smokers, past smokers, or nonsmokers. Hypertension was also diagnosed during the biennial study clinical examinations. All participants underwent medical screening by a physician at least once annually, and hypertension was also diagnosed by the physicians. Hypertension was defined by using World Health Organization criteria as physician-diagnosed hypertension (systolic blood pressure 160 mm Hg, diastolic blood pressure 95 mm Hg, or both) or use of antihypertensive medication (16). Statistical Analysis Age-adjusted mean values and relevant population characteristics were computed for the duration of the walk to work by using analysis of covariance for continuous variables and the direct method for categorical variables. For each participant, person-years of follow-up were counted from the date at study entry to the date of diagnosis of hypertension or 1 April 1997, whichever came first. The rate of follow-up was 94% of the total potential person-years of follow-up. Multivariate Cox proportional-hazards regression models were used to evaluate the simultaneous effects of the duration of the walk to work, the frequency of leisure-time physical activity, age, body mass index, daily alcohol consumption, smoking status, and fasting plasma glucose level. Baseline systolic and diastolic blood pressure were not included in our primary analyses because they could presumably be in the causal pathway between the exposures (such as physical activity, age, body mass index, and alcohol consumption) and risk for hypertension. However, we included systolic and diastolic blood pressure in further models to assess the effect of physical activity on the risk for hypertension independent of their effects on systolic and diastolic blood pressure. The linear trends in risks were evaluated by entering indicators for each categorical level of exposure or by using the median value for each category. As a reference category, we used men with the lowest level of physical activity. To address the potential misclassification of leisure-time physical activity over time, additional analyses were performed on the basis of the data at both study entry (1981 to 1990) and the examination done 4 years after (1985 to 1994) each participant was enrolled. We also performed analyses that excluded participants who developed hypertension between study entry (1981 to 1990) and the third examination done 4 years later (1985 to 1994). We calculated the 95% CI for each relative risk (17), and all P values are two-tailed. Statistical analyses were performed by using the SPSS 7.5J software package (SPSS, Inc., Chicago, Illinois). We estimated the number needed to walk, a value analogous to the number needed to treat. The number needed to treat for a given therapy is the reciprocal of the absolute risk reduction for that treatment (18). A 95% CI for the number needed to treat is obtained simply by taking reciprocals of the values defining the 95% CI of the absolute risk reduction (19). In our study, the number needed to walk was defined as the number of men who would have to adopt walking to avoid a single case of hypertension. The number needed to treat must always be based on an outcome for a specific period of time (20); thus, in estimating the number needed to walk, we chose an observation period of 10 years between study entry (1981 to 1986) and the examination done 10 years after (1991 to 1996) each participant was enrolled. Role of the Funding Source The funding agencies did not participate in the collection, analysis, or interpretation of data presented in this report or in the decision to submit the manuscript for publication. Results Of the 6104 men eligible for this study between 1981 and 1990, we excluded 87 men who did not undergo medical check-ups during the follow-up period. The study sample for analysis consisted of 6017 men. During the 59 784 person-years of follow-up between 1981 and 1997, 626 men developed hypertension. As the duration of the walk to work increased, body weight and the body mass index decreased (P for trend=0.037 and 0.035, respectively) (Table 1). We identified no significant relation between the duration of the walk to work and the levels of leisure-time physical activity (P for trend=0.062). Table 1. Baseline Characteristics according to Duration of the Walk to Work Duration of the Walk to Work The duration of the walk to work was associated with a decreased risk for incident hypertension (Table 2). After adjustment for age, body mass index, daily alcohol consumption, smoking status, frequency of leisure-time physical activity, systolic blood pressure, diastolic blood pressure, and fasting plasma glucose level, the relative risk for hypertension was 0.71 (95% CI, 0.52 to 0.97) in men whose walk to work lasted 21 minutes or more compared with those whose

Combined Measurement of Fasting Plasma Glucose and A1C Is Effective for the Prediction of Type 2 Diabetes: The Kansai Healthcare Study

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.

Impact of cigarette smoking on the incidence of Type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey

Aims To assess the impact of cigarette smoking on the incidence of Type 2 diabetes mellitus (DM) in middle‐aged Japanese men.

Leisure‐time physical activity at weekends and the risk of Type 2 diabetes mellitus in Japanese men: the Osaka Health Survey

Aims To investigate association between leisure‐time physical activity at weekends and the risk of developing Type 2 diabetes mellitus (DM).

Genotoxicity of beryllium, gallium and antimony in short-term assays

The genotoxicity of beryllium, gallium and antimony compounds was studied with the rec, Salmonella mutagenicity and SCE assays. In the rec assay, all the salts of the metals, BeCl2, Be(NO3)2, GaCl3, Ga(NO3)3, SbCl3, SbCl5, and an oxide, Sb2O3, had DNA-damaging activity. None of the compounds was mutagenic to Salmonella. In the SCE assays using V79 cells, 2 antimony(III) compounds, SbCl3 and Sb2O3, and 2 beryllium compounds, BeCl2 and Be(NO3)2, induced SCEs significantly. Sb2O3, slightly soluble in water, was positive in both the rec assay and the SCE assay at very low doses.

Lower Serum Creatinine Is a New Risk Factor of Type 2 Diabetes : The Kansai Healthcare Study

OBJECTIVE—Because skeletal muscle is one of the target tissues for insulin, skeletal muscle mass might be associated with type 2 diabetes. Serum creatinine is a possible surrogate marker of skeletal muscle mass. The purpose of this study was to determine whether serum creatinine level is associated with type 2 diabetes. RESEARCH DESIGN AND METHODS—The study participants were nondiabetic Japanese men (n = 8,570) aged 40–55 years at entry. Type 2 diabetes was diagnosed if fasting plasma glucose was ≥126 mg/dl or if participants were taking oral hypoglycemic medication or insulin. RESULTS—During the 4-year follow-up period, 877 men developed type 2 diabetes. Lower serum creatinine was associated with an increased risk of type 2 diabetes. The multiple-adjusted odds ratio for those who had serum creatinine levels between 0.40 and 0.60 mg/dl was 1.91 (95% CI 1.44–2.54) compared with those who had levels between 0.71 and 0.80 mg/dl. CONCLUSIONS—Lower serum creatinine increased the risk of type 2 diabetes.

URINARY EXCRETION OF ARSENIC METABOLITES AFTER LONG-TERM ORAL ADMINISTRATION OF VARIOUS ARSENIC COMPOUNDS TO RATS

The metabolism of arsenic compounds in rats was studied by comparing urinary metabolites of arsenic compounds administered for 1 wk or 7 mo. Male F344/DuCrj rats were given 100 mg As/L as monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), trimethylarsine oxide (TMAO), or arsenobetaine (AsBe), or 10 mg As/L as arsenite [As(III)] via drinking water for 7 mo. Urine was collected by forced urination after 1 wk or 7 mo. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry. In the case of As(III) ingestion, a small portion of all arsenic excreted in urine (about 6%) was excreted in inorganic form, while most arsenic was excreted as methylated arsenic metabolites. Following MMA treatments for 1 wk or 7 mo, the predominant products excreted were unchanged MMA and DMA accompanied by small amounts of TMAO and tetramethylarsonium (TeMA). In the case of DMA treatment the urinary compounds found were mainly the parent DMA and TMAO with minute amounts of TeMA. TMAO was methylated to TeMA to a slight extent after 1 wk and 7 mo of administration, although most TMAO was excreted in the form of unchanged TMAO. AsBe was predominantly eliminated in urine without any transformation. Two unidentified metabolites were detected in urine after 7 mo of arsenic species exposure; the amounts of these metabolites increased in the order DMA > MMA > TMAO with only small quantities of these detected in the As(III)-treated group. These results suggest that these unidentified metabolites are formed during a demethylation process, and not during methylation. Our findings indicate that long-term exposure to As(III), MMA, or DMA decreases the proportion of TMAO elimination in urine and increases that of DMA, M-1, and M-2, and that further methylation to TMAO to TeMA does occur to a slight extent following long-term exposure to arsenical compounds in rats.

Determination of arsenic compounds using inductively coupled plasma mass spectrometry with ion chromatography

A combined system of inductively coupled plasma mass spectrometry (ICP-MS) with ion chromatography (IC) has been used for the determination of arsenic compounds. Arsenous acid (AsIII), monomethylarsonic acid (MMAs), dimethylarsinic acid (DMAs), trimethylarsine oxide (TMAsO) and arsenobetaine were separated by anion-exchange chromatography. Subsequently eluates were directly introduced into ICP-MS and detected at m/z 75. Separation parameters were optimized for the arsenic compounds as follows: column, two Excelpak ICS-A35 columns (150 mm × 4.6 mm I.D. each) packed with polymer-based hydrophilic anion-exchange resin (ion-exchange capacity: 0.15 mequiv. /g dry); mobile phase, 10 · 10−3M tartaric acid; flow-rate, 1.0 ml/min; column temperature, 50°C; injection volume, 20 μl. The detection limits for the five arsenic compounds were from 0.22 to 0.44 μ/l as an As element. The repeatability was better than 5% (relative standard deviation) for all arsenic compounds. The IC-ICP-MS system was applied to the determination of arsenic compounds in the urine of DMAs-exposed rats. AsIII, MMAs, DMAs and TMAsO were detected in the urine.

Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan.

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.