Published papers

Aims Acute administration of oolong tea decreases blood glucose levels. We investigated the association between long-term oolong tea intake and subsequent risk of developing diabetes among men of working age. Methods Data were analysed from a cohort of participants in the High-risk and Population Strategy for Occupational Health Promotion Study (HIPOP-OHP), conducted in Japan from 1999 to 2004. Oolong tea intake at baseline and subsequent risk of diabetes was evaluated using a Cox proportional hazards model. Results Of 4975 male workers, a total of 201 cases of diabetes were reported over a median of 3.4years of follow-up. Mean age and BMI of all participants at baseline were 38.3years and 22.9kg/m 2, respectively. Compared with those not consuming oolong tea, multivariable adjusted hazard ratios for developing diabetes were 1.00 (95%CI 0.67-1.49) for those who drank one cup of oolong tea per day and 1.64 (95%CI 1.11-2.40) for those drinking two or more cups per day. Fasting blood glucose increment per year was 0.11mmol/l (95%CI 0.09-0.12mmol/l), 0.12mmol/l (95%CI 0.09-0.15mmol/l) and 0.15mmol/l (95%CI 0.11-0.18mmol/l), respectively, for oolong tea consumption of 0, 1 and ≥2cups/day, with a significant linear trend (P<0.0001). Conclusions Long-term consumption of oolong tea may be a predictive factor for new onset diabetes. Further studies are necessary to elucidate the role of oolong tea in the risk of developing diabetes. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Objective: Serum 1,5-anhydro-d-glucitol (1,5-AG) is well-known to be a useful clinical marker of both short-term glycemic status and postprandial hyperglycemia. In addition, previous epidemiological studies have shown that an increased postload glucose level in an oral glucose tolerance test is a risk factor for cardiovascular diseases (CVD). However, no previous prospective study has reported the association between serum 1,5-AG levels and the risk of CVD. In this study, we examined whether serum 1,5-AG levels can predict the incidence of first-ever CVD. Methods: Our study was a population-based cohort study in an urban area of Japan. Study subjects comprised 2095 initially healthy Japanese (991 men and 1104 women, mean age: 58.5 years) with no history of coronary heart disease (CHD) or stroke. They were followed up for an average of 11.1 years, and 147 CVD events (64 CHD and 83 strokes) were observed. Results: The adjusted hazard ratios (HRs) of all CVD in men increased linearly (p= 0.004). The HR in the category with serum 1,5-AG levels of 14.0 μg/mL or less was 2.22 (95% confidence interval; 1.24-3.98) compared to the reference category (24.5 μg/mL or greater). Similar results were also shown with a sensitivity analysis in non-diabetic men. Conversely, no significant relationship between serum 1,5-AG levels and CVD risks was observed in women. Conclusions: Our results suggest that measurement of serum 1,5-AG levels is useful to detect individuals, especially men, at higher risk for CVD, regardless of the presence or absence of diabetes. © 2011 Elsevier Ireland Ltd.

Aim: There have been few studies on the relationships of the dietary polyunsaturated to saturated fatty acid ratio (P/S) to cardiovascular risk factors and metabolic syndrome. We hypothesized that there would be favorable relationships. & Methods: Metabolic cardiovascular risk factors from dietary nutrient intake were investigated in 1,004 men and women aged 40-59 years from 4 population samples of Japanese. Multiple linear regression analysis was used to examine the relationship of the dietary P/S ratio to the following risk factors: hemoglobin A1c, blood pressure, serum triglycerides, LDL and total cholesterol, and HDL-cholesterol. Adjusted odds ratio of having metabolic syndrome was also calculated. & Results: The dietary P/S ratio was significantly and inversely related to serum total and LDL cholesterol with control for possible confounding variables. We did not find any significant relationship between the P/S ratio and single metabolic risk factors or the prevalence of metabolic syndrome. & Conclusions: Managing the P/S ratio is important to control serum LDL-cholesterol; however, increasing the P/S ratio may not improve metabolic risk factors. Other countermeasures, such as weight control, greater physical activity, and smoking cessation should be recommended to prevent and control metabolic syndrome.

Aim: To clarify the relationship between the accumulation of cardiovascular risk factors and the 5-year decline in instrumental activity of daily living (IADL) among a cohort representative of the Japanese population aged 65 years and over. Methods: An IADL survey was performed by public health centers throughout Japan. Study subjects were elderly men and women living in districts under the jurisdiction of collaborating health centers. Subjects were invited to participate in the IADL survey assessed by the Tokyo Metropolitan Institute of Gerontology (TMIG) Index of Competence twice in 1995 and in 2000; 1222 participants were eligible for the analysis. The relationship between the number of cardiovascular risk factors, such as hypertension, hypercholesterolemia, hypertriglycemia, low serum high-density lipoprotein cholesterol, diabetes, obesity and smoking, at baseline and the 5-year difference in IADL scores was examined by linear regression analysis and logistic regression analysis. Results: Decrease in IADL scores was larger in those with cardiovascular risk factors than in those without. The multivariable odds ratio (OR) for decreased IADL after adding one CVD risk factor was 1.16 (95% confidence interval (CI), 1.04-1.29) after adjusting for age, sex, alcohol consumption and TMIG score at baseline. Among participants who were regarded as physically independent with respect to basic ADL in the baseline survey, the odds ratio was also similar and significant. Conclusion: Preventive interventions directed against cardiovascular risk factors, especially against their accumulation, may contribute to maintaining IADL in the Japanese elderly.

Aim: Gamma-glutamyltransferase (GGT) is known to correlate well with alcohol consumption; however, the relation between GGT and diabetes and that between alcohol consumption and diabetes mellitus (DM) is inconsistent. Thus, several questions, such as whether light to moderate drinkers can be considered as low risk for diabetes incidence irrespective of their GGT level, is unresolved. In this study, we investigated the relation of GGT or alcohol drinking with DM incidence considering the body mass index (BMI) in healthy Japanese workers. Methods: We followed 3095 men who did not have DM at baseline for 4 years. Incident diabetes was defined as a fasting (non-fasting) plasma glucose level of ≥7.0 (11.1) mmol/L, or treatment of diabetes. Multiple adjusted hazard ratios (HR) were calculated using Cox proportional models. Results: Participants with higher GGT (GGT ≥27 IU/L) showed an increased risk of diabetes incidence even when their BMI level was low. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers (alcohol <23 g/day) was not low if they were either overweight (BMI ≥25 kg/m2) or had higher GGT (HR= 2.60, p= 0.08) or both overweight and higher GGT (HR= 3.16, p= 0.07) compared with never drinkers without higher GGT and overweight. Conclusions: Higher GGT was associated with a higher incidence of DM irrespective of drinking status or obesity. Although a U-shaped relation between alcohol drinking and incident diabetes was observed, the risk to light to moderate drinkers was not low if they were either overweight or had higher GGT.

Aim: It is well established that people gain weight after smoking cessation; however, changes in cardiovascular risk factors and the estimated risk of coronary heart disease following smoking cessation have yet to be fully clarified. Methods: The participants were 1,995 Japanese male workers at 11 workplaces who participated continuously in the High-risk and Population Strategy for Occupational Health Promotion (HIPOPOHP) study. Participants with a smoking habit had cardiovascular risk factors measured at baseline and over a 4-yr period. Their estimated incidence risk of coronary heart disease was calculated by a formula based on a previous cohort study. Results: Successful abstainers who had stopped smoking for at least 6 months at the end of the follow-up period had weight gains of approximately 2 kg. These subjects had significant worsening of the following factors compared to continuing smokers: systolic and diastolic blood pressure, total cholesterol, triglyceride and fasting blood sugar levels. In contrast, HDL-cholesterol levels improved significantly. When the overall instantaneous incidence risk of coronary heart disease prior to smoking cessation was assumed to be 1.00, the estimated risk was 0.76 (95%CI: 0.68-0.85) in successful abstainers due mainly to smoking cessation, despite weight gain. Conclusion: Although smoking cessation leads to weight gain, the estimated risk of coronary heart disease was decreased markedly by smoking cessation.

Background: Although prevention of heart failure (HF) is an urgent public health need with national and global implications, population-based studies are rare. Methods and results: We studied risk factors for HF and coronary heart disease (CHD) mortality using the NIPPON DATA80 database with a 24-year follow-up. At the baseline in 1980, data were collected on study participants aged 30 years and over from randomly selected areas in Japan. We followed 9300 participants (44% men, mean age 51). Over the 24-year follow-up, there were 189 deaths from HF (82 men and 107 women) and 188 (91 men and 97 women) from CHD. Cox analyses revealed common and specific risk factors for both mortalities. Common risk factors were: systolic blood pressure for male HF (hazard ratio: 1.28 per 1SD, P = 0.02) and for CHD in both (men: 1.20, P = 0.01; women: 1.27, P = 0.003), smoking for male CHD (1.31, P = 0.004) and for female HF (1.39, P = 0.01), blood sugar for HF and CHD in men (HF: 1.21 per 1SD, P = 0.009; CHD: 1.29, P < 0.0001); T wave abnormality in male HF (2.33, P = 0.003) and female CHD (1.84, P = 0.001). Specific risk factors were: serum creatinine for HF in both (men: 1.14 per 1SD, P < 0.0001, women: 1.09, P = 0.01); total cholesterol for CHD in men (1.38 per 1SD, P = 0.001), history of valvular heart disease (6.48, P = 0.002) or stroke (2.41, P = 0.048) in male HF, and history of angina in female CHD (3.59, P = 0.003). Conclusion: Common and specific measures need to be undertaken to prevent HF and CHD mortality. © 2010 Published by Elsevier Ltd. on behalf of World Heart Federation.

Few studies have reported the relationship between smoking in middle age and long-term risk of impaired activities of daily living (ADL). We analyzed 2,276 men and women aged 47-59 years at the baseline survey of NIPPON DATA80 in 1980. At the follow-up survey in 1999, ADL was surveyed among 1890 survivors. Multivariate-adjusted odds ratio (AOR) and 95% CI of impaired ADL or of composite outcome of either death or impaired ADL according to baseline smoking status were calculated by multiple logistic regression analyses. In 1999, 386 participants were dead, and 75 participants had impaired ADL. Compared with nonsmokers, AOR (95% CI) of impaired ADL was significantly higher in current smokers at baseline (odds ratio [OR] 2.11 [1.09-4.06]). Compared with nonsmokers, AOR of impaired ADL was higher as the number of cigarettes increased (OR 2.04 [1.02-4.06] for <20 cigarettes/day and OR 2.35 [0.94-5.88] for >20 cigarettes/day; p for trend = .04). AOR of composite outcome for current smoking was 1.83 (1.37-2.41). Smoking in middle age would increase future risks of impaired ADL. Smoking cessation may be important to prevent future impairment of ADL as well as death.

Evidence of the causal relationship between hypercholesterolemia and coronary artery disease (CAD) has been established worldwide. However, little attention has been paid to the relationship between hypercholesterolemia and stroke, despite stroke being the most common cardiovascular disease in Japan. We therefore reviewed cohort studies that investigated this relationship in the Japanese population over the past 20 years, and compared their findings with clinical trials and cohort studies in Western countries. Fourteen cohort studies were carried out in Japan during this period. The number of subjects in the studies ranged from 1621 to 91,219 and the mean follow-up period ranged from 7.6 to 32 years. The majority of studies showed no association between hypercholesterolemia and total stroke. However, one report showed a positive association between low-density lipoprotein cholesterol and atherothrombotic cerebral infarction. The relationship between hypercholesterolemia and cerebral infarction may be modified by the proportion of atherothrombotic infarctions in the population surveyed. Randomized controlled trials on statins have shown a substantial reduction in cerebral infarction, and so the discrepancy between cohort studies and clinical trials requires further study. However, some studies have reported that subjects with low blood cholesterol are more susceptible to intracerebral hemorrhage. Two hypotheses have been proposed to explain this association between low cholesterol and intracerebral hemorrhage. First, low blood cholesterol may induce angionecrosis, possibly in combination with hypertension, and second, low blood cholesterol may reflect a poor nutritional status. Either way, further continuous research in various fields of medical science is required to clarify the overall effect of blood cholesterol on stroke in humans. © 2012 by The Keio Journal of Medicine.

Background and Aims: Previously, we found significantly higher serum leptin in Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether differences in dietary and other lifestyle factors explain higher serum leptin concentrations in Japanese living a Western lifestyle in Hawaii compared with Japanese in Japan. Methods and Results: Serum leptin and nutrient intakes were examined by standardized methods in men and women ages 40-59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression models were used to assess role of dietary and other lifestyle traits in accounting for serum leptin difference between Hawaii and Japan. Mean leptin was significantly higher in Hawaii than Japan (7.2 ± 6.8 vs 3.7 ± 2.3 ng/ml in men, P < 0.0001; 12.8 ± 6.6 vs 8.5 ± 5.0 in women <0.0001). In men, higher BMI in Hawaii explained over 90% of the difference in serum leptin; in women, only 47%. In multiple linear regression analyses in women, further adjustment for physical activity and dietary factors - alcohol, dietary fiber, iron - produced a further reduction in the coefficient for the difference, total reduction 70.7%; P-value for the Hawaii-Japan difference became 0.126. Conclusion: The significantly higher mean leptin concentration in Hawaii than Japan may be attributable largely to differences in BMI. Differences in nutrient intake in the two samples were associated with only modest relationship to the leptin difference. © 2010 Elsevier B.V.