Kozue Nakamura

Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women

Although the inverse association between coffee consumption and risk of diabetes has been reported numerous times, the role of caffeine intake in this association has remained unclear. We evaluated the consumption of coffee and other beverages and food containing caffeine in relation to the incidence of diabetes. The study participants were 5897 men and 7643 women in a community-based cohort in Takayama, Japan. Consumption of coffee, green tea, oolong tea, black tea and chocolate snacks were measured with a semi-quantitative FFQ in 1992. At the follow-up survey in 2002, the development of diabetes and the time of diagnosis were reported. To assess the association, age, smoking status, BMI, physical activity, education in years, alcohol consumption, total energy intake, fat intake and womens menopausal status were adjusted. Among men who consumed one cup per month to six cups per week and among those who consumed one cup per d or more, the associated hazard ratios were 0.69 (95 % CI 0.50, 0.97) and 0.69 (95 % CI 0.49, 0.98) compared with those who drank little to no coffee, with a P value for trend of 0.32. The hazard ratios for women with the same coffee consumption patterns were 1.08 (95 % CI 0.74, 1.60) and 0.70 (95 % CI 0.44, 1.12), with a P value for trend of 0.03. The association between estimated total caffeine intake and risk of diabetes was insignificant both among men and among women. The results imply that coffee consumption decreased the risk of developing diabetes. The protective effect may exist aside from the influence of caffeine intake.

Dietary glycemic index, glycemic load, and intake of carbohydrate and rice in relation to risk of mortality from stroke and its subtypes in Japanese men and women

We assessed the relationship of the dietary glycemic index (GI), glycemic load (GL), and intake of carbohydrate and rice, and risk of mortality from stroke and its subtypes. The cohort consisted of 12,561 men and 15,301 women residing in Takayama, Japan, in 1992. At the baseline, a food frequency questionnaire was administered; and the dietary GI, GL, and intake of carbohydrates and rice were estimated. Deaths from stroke occurring in the cohort were prospectively noted until 1999 with data from the office of the National Vital Statistics. The risk of mortality from stroke was assessed with a Cox proportional hazard model after adjusting for age; body mass index; smoking status; physical activity; history of hypertension; education; and intake of total energy, alcohol, dietary fiber, salt, and total fat. The risk of stroke subtypes was assessed in the age-adjusted model. The hazard ratios of total stroke comparing the highest vs the lowest quartiles of the dietary GI were 0.78 (95% confidence interval [CI], 0.41-1.47) with P(trend) = .50 in men and 2.09 (95% CI, 1.01-4.31) with P(trend) = .10 in women. Among women, the association was also significant with the risk of ischemic stroke (hazard ratio = 2.45; 95% CI, 1.01-5.92; P(trend) = .03); and a significant positive trend was also observed between dietary GL and mortality from hemorrhagic stroke (P(trend) = .05). The current study implies that diets with a high dietary GI increase the risk of mortality from stroke among Japanese women.

Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study.

The effects of soy or isoflavone intake on breast cancer need to be examined further in epidemiologic studies. We assessed the associations of soy and isoflavone intake with breast cancer incidence in a population‐based prospective cohort study in Japan. Participants were members from the Takayama study, aged 35 years or older in 1992. The follow‐up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008. Cancer incidence was mainly confirmed through regional population‐based cancer registries. Breast cancer was defined as code C50 according to ICD‐10. Soy and isoflavone intakes were assessed with a validated food frequency questionnaire. Using the Cox proportional hazard models, the association of soy and isoflavone intake with breast cancer was assessed after adjustments for age, body mass index, physical activity, smoking, alcohol consumption, education, age at menarche, age at first delivery, menopausal status, number of children and history of hormone replacement therapy. Among the 15,607 women analyzed, 172 had developed breast cancer. The relative risks of postmenopausal breast cancer were lower among women with higher intakes of soy (trend p = 0.023) and isoflavone (trend p = 0.046), although the relative risks of premenopausal breast cancer were not associated with intakes of soy and isoflavone. Decreased risks of breast cancer were found even among women with a moderate intake of soy and isoflavone. These results suggested that soy and isoflavone intakes have a protective effect on postmenopausal breast cancer.

Diabetes mellitus and cancer risk: pooled analysis of eight cohort studies in Japan.

Although a growing body of evidence suggests a link between diabetes and cancer, it is not clear whether diabetes independently increases the risk of cancer. We conducted a comprehensive assessment of the association between pre‐existing diabetes and total and site‐specific cancer risk based on a pooled analysis of eight cohort studies in Japan (>330 000 subjects). We estimated a summary hazard ratio by pooling study‐specific hazard ratios for total and site‐specific cancer by using a random‐effects model. A statistically increased risk was observed for cancers at specific sites, such as colon (hazard ratio; HR = 1.40), liver (HR = 1.97), pancreas (HR = 1.85) and bile duct (HR = 1.66; men only). Increased risk was also suggested for other sites, and diabetes mellitus was associated with an overall 20% increased risk in total cancer incidence in the Japanese population. The association between these two diseases has important implications for reiterating the importance of controlling lifestyle factors and may suggest a possible strategy for cancer screening among patients with diabetes. Studies continuously investigating the risk factors for diabetes are also important.

Association of intakes of fat, dietary fibre, soya isoflavones and alcohol with uterine fibroids in Japanese women.

Certain dietary components which could affect oestrogen may have implications in the aetiology of uterine fibroids. We previously found that soya intake was inversely associated with a subsequent risk of hysterectomy, suggesting a potentially protective effect of soya against uterine fibroids, the major clinical indication for hysterectomy. We cross-sectionally assessed the associations of intakes of fat, soya foods, dietary fibre and alcohol with uterine fibroids. Study subjects were 285 premenopausal Japanese women participating in a health-check up programme, including gynaecological examinations, provided by a general hospital between October 2003 and March 2006. The presence of fibroids was confirmed by transvaginal sonogram. If women had undergone hysterectomy, self-report of fibroids was accepted. Each subjects usual diet, including alcohol, was determined with the use of a validated FFQ. Fifty-four women were identified as prevalent cases of fibroids or having had hysterectomy due to fibroids. The mean alcohol intake was statistically significantly higher among women with fibroids than among those without fibroids after controlling for known or suspected risk factors. For the highest compared with the lowest tertile of alcohol intake, the OR of uterine fibroids was 2.78 (95% CI 1.25, 6.20). There was no significant association of intake of fats, soya isoflavones or dietary fibre with uterine fibroids. The data suggest that higher alcohol intake is associated with a higher prevalence of uterine fibroids. Further studies on diet, especially phyto-oestrogens, and uterine fibroids are needed given the limited data currently available.

Branched-chain Amino Acid Intake and the Risk of Diabetes in a Japanese Community The Takayama Study

Dietary supplementation with branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, has shown potential benefits for the metabolic profile. However, higher blood BCAA levels have been associated with insulin resistance. To our knowledge, there has been no study on dietary BCAAs and the risk of diabetes. We examined the association between BCAA intake and risk of diabetes in a population-based cohort study in Japan. A total of 13,525 residents of Takayama City, Japan, who enrolled in a cohort study in 1992 responded to a follow-up questionnaire seeking information about diabetes in 2002. Diet at baseline was assessed by means of a validated food frequency questionnaire. A high intake of BCAAs in terms of percentage of total protein was significantly associated with a decreased risk of diabetes in women after controlling for covariates; the hazard ratio for the highest tertile versus the lowest was 0.57 (95% confidence interval: 0.36, 0.90; P-trend = 0.02). In men, leucine intake was significantly marginally associated with the risk of diabetes; the hazard ratio for the highest tertile versus the lowest was 0.70 (95% confidence interval: 0.48, 1.02; P-trend = 0.06). Data suggest that a high intake of BCAAs may be associated with a decrease in the risk of diabetes.

Cigarette smoking and other lifestyle factors in relation to the risk of pancreatic cancer death: a prospective cohort study in Japan.

OBJECTIVE To examine the association of smoking and lifestyle factors with pancreatic cancer death in the prospective design. METHODS Mortality from pancreatic cancer in regard to smoking, body mass index, physical activity, and alcohol, coffee and green tea intake, was studied in a prospective cohort of 30,826 inhabitants in Takayama, Japan. In 1992, each subject completed a self-administered questionnaire on demographic information, smoking, drinking habits, diet, exercise and medical histories. The response rate was 85.3%. RESULTS From 1992 to 1999, 33 men and 19 women died due to pancreatic cancer. Hazard ratios and 95% confidence intervals were determined using Cox proportional hazards models. Women who were defined as current smokers at baseline had significant and increased risk of pancreatic cancer death after adjustment for age, body mass index and history of diabetes mellitus (Hazard ratio: 4.77, 95% confidence intervals: 1.58-14.4). There were significant positive associations of pancreatic cancer death with the years of smoking and the number of cigarettes consumed daily in women in a dose-dependent manner. Current smokers indicated a non-significant risk increase in men (Hazard ratio: 3.81, 95% confidence intervals: 0.88-16.6). Body mass index, physical activity, and alcohol, coffee and green tea intake were not significantly associated with pancreatic cancer death. CONCLUSIONS These data suggested that smoking increases the risk of death from pancreatic cancer in Japanese women.

Consumption of vegetables alters morning urinary 6-sulfatoxymelatonin concentration.

Abstract:  Melatonin, which is contained in certain vegetables, may have an influence on circulatory melatonin concentrations. This study examined the effects of the consumption of vegetables on 6‐sulfatoxymelatonin concentrations in morning urine. Ninety‐four healthy women aged 24–55 were recruited through a city public health center in Japan. The women randomly allocated to the intervention group were requested to consume high amounts of six selected vegetables, with a target of 350 g/day for 65 days, while those in the control group were asked to avoid the same six vegetables during the same period. First‐void morning urine was collected before and at the end of the intervention period, and creatinine‐adjusted 6‐sulfatoxymelatonin concentrations were measured. At the end of the intervention period, daily mean intake of melatonin from the six vegetables was 1288.0 ng in the intervention group and 5.3 ng in the control group. In the intervention group, the mean concentration of 6‐sulfatoxymelatonin changed from 48.1 [95% confidence interval (CI): 40.4–57.2] ng/mg creatinine to 49.6 (95% CI: 42.8–57.3) ng/mg creatinine across the intervention period. In the control group, the mean concentration of 6‐sulfatoxymelatonin changed from 55.5 (95% CI: 48.7–63.2) ng/mg creatinine to 50.8 (95% CI: 44.0–58.7) ng/mg creatinine across the intervention period. A comparison of the two groups with regard to the changes in the 6‐sulfatoxymelatonin concentrations across the intervention period showed a significant difference (P = 0.03). The results indicate that increased consumption of vegetables raises circulatory melatonin concentrations.

Susceptibility to 6‐MP toxicity conferred by a NUDT15 variant in Japanese children with acute lymphoblastic leukaemia

Genotyping of TPMT prior to 6‐mercaptopurine (6‐MP) administration in acute lymphoblastic leukaemia (ALL) patients has been integrated into clinical practice in some populations of European ancestry. However, the comparable rates of 6‐MP myelotoxicity, but rarity of TPMT variants, in Asians suggest that major determinants have yet to be discovered in this population. We genotyped 92 Japanese paediatric ALL patients for NUDT15 rs116855232, a 6‐MP toxicity‐related locus discovered in Asians. Logistic regression and survival analysis were used to evaluate its association with leucopenia, hepatotoxicity, 6‐MP dose reduction, therapy interruption and event‐free survival. The allele frequency of rs116855232 was 0·16, and leucopenia was more common in carriers of the T allele (odds ratio, 7·20; 95% confidence interval, 2·49–20·80; P = 2·7 × 10−4). As leucopenia results in 6‐MP dose reduction, we observed average doses during maintenance therapy of 40·7, 29·3 and 8·8 mg/m2 for patients with CC, CT and TT genotypes, respectively (P < 0·001). Hepatotoxicity was observed only in CC genotype patients. Event‐free survival did not significantly differ by NUDT15 genotype. rs116855232 is an important determinant of 6‐MP myelotoxicity in Japanese children with ALL and may represent the most robust toxicity‐related locus in Asians to date. Considerations for clinical application may be warranted.

Prevalence of Tinnitus in Community-Dwelling Japanese Adults

Background Several studies have reported the prevalence of tinnitus among general populations; however, most of these studies were conducted in Europe or the United States. We estimated the prevalence of tinnitus among the general adult population in Japan. Methods The subjects were participants in the Takayama Study, a population-based cohort study. In 2002, a total of 14 423 adults (6450 men and 7973 women) aged 45 to 79 years responded to a self-administered questionnaire that inquired about history of tinnitus, which was defined as episodes lasting longer than 5 minutes, excluding those occurring immediately after noise exposure. Respondents were also asked about the loudness and severity of tinnitus. Results Overall, 11.9% of the subjects reported having tinnitus; the percentage was somewhat higher among men (13.2%) than women (10.8%). The prevalence of tinnitus increased with age in both sexes. Approximately 0.4% of the overall population reported that tinnitus had a severe effect on their ability to lead a normal life. Medical history of hypertension or ischemic heart diseases, use of steroid or antihypertensive medication, and employment as a factory worker or machine operator were associated with tinnitus status in both men and women. Conclusions Tinnitus is relatively common in Japan. Although the use of various definitions of tinnitus in different studies makes it difficult to compare prevalence among populations, the present prevalence estimate was similar to those in studies in Europe and the United States.