Associations of Plasma 25-Hydroxy Vitamin D and Dietary Vitamin D Intake with Insulin Resistance in Healthy Japanese Women.

We investigated the associations of plasma 25-hydroxy vitamin D (25(OH)D) concentration and the dietary intake of vitamin D with insulin resistance in Japanese women. Study participants were 406 Japanese women attended a health examination. They were not taking hormones or medications for diabetes and had no history of cancer, ischemic heart disease, or stroke. Information regarding medical history and lifestyle factors was obtained by a self-administered questionnaire, while hours of sun exposure were determined through interviews. Dietary intake of vitamin D was evaluated using a validated food frequency questionnaire. Fasting plasma glucose and insulin concentrations were measured, and insulin resistance (HOMA-IR) scores were calculated based on homeostasis model assessment. Women with vitamin D deficiency (25(OH)D<20 ng/mL) had significantly higher fasting plasma insulin concentration and HOMA-IR than did the other women. Plasma 25(OH)D concentration was significantly and inversely associated with fasting plasma insulin level and HOMA-IR after controlling for age, season, menopausal status, BMI, smoking status, alcohol intake, physical exercise, and intakes of fat and calcium. Dietary vitamin D intake was not associated with HOMA-IR concentration after adjusting for these covariates and hours of sun exposure. Although significant inverse association between plasma 25(OH)D concentration and HOMA-IR was observed in women with a low BMI, low fat intake, or a high calcium intake, the interaction terms were not statistically significant. Data suggest that plasma vitamin D, but not dietary vitamin D, is inversely associated with fasting plasma insulin concentration and HOMA-IR in non-diabetic Japanese women.

Sleep-related factors and circulating levels of sex hormones in premenopausal Japanese women.

Sleep disruption and circadian disruption have been proposed to be risk factors of breast cancer. The present study examined the associations of sleep-related factors, referring to night shift work, sleep habits, and sleep disturbances, with the plasma levels of sex hormones in premenopausal Japanese women. Study participants were 432 women who had regular menstrual cycles less than 40 days long. Information on their history of night shift work and sleep disturbances was obtained using a self-administered questionnaire. Information on their sleep habits, such as usual wake-up times, bedtimes, and ambient light level while sleeping, was obtained in an interview. The participants' height and weight were measured. Plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), FSH, and LH were also measured. After controlling for the phase of the menstrual cycle and other covariates, more years of night shift work ≥ once a week during the past 10 years was significantly associated with a lower SHBG and a higher free estradiol level. Shorter sleep duration was significantly associated with the higher total, bioavailable, and free testosterone levels. Sleep disturbance by awaking after sleep onset was significantly associated with a high free estradiol level. The data suggest that long-term night shift work, short sleep duration, and arousal during sleep are associated with higher estradiol or testosterone levels in premenopausal women.

Associations of urinary cadmium with circulating sex hormone levels in pre- and postmenopausal Japanese women.

BACKGROUND: Exposure to cadmium has been suspected as a risk factor for breast cancer. The present study examined the associations between urinary cadmium levels and circulating sex hormone levels that are linked to breast cancer risk in healthy women. METHODS: The study subjects were 396 premenopausal Japanese women who had regular menstrual cycles less than 40 days long and 207 postmenopausal Japanese women. Urinary cadmium was measured using spot urine samples. Plasma estradiol, testosterone, and dehydroepiandrosterone sulfate were measured. Additionally, the follicle-stimulating hormone, luteinizing hormone, and sex hormone-binding globulin were measured for premenopausal women. RESULTS: In premenopausal women, the urinary cadmium level either expressed in µg per liter or per g of urine creatinine was significantly inversely associated with total and free testosterone levels after controlling for age, body mass index, smoking status, alcohol intake, and the phase of the menstrual cycle. Total and free testosterone levels were 14.6% and 15.0% lower, respectively, in women in the highest quartile of urinary cadmium per g creatinine in those in the lowest quartile. In postmenopausal women, the urinary cadmium in µg per liter as well as per g creatinine was significantly inversely associated with the estradiol level after controlling for covariates. The estradiol level was 25.8% lower in women in the highest tertile of urinary cadmium per g creatinine than in those in the lowest tertile. CONCLUSIONS: The data suggest inverse associations between urinary cadmium and the plasma estradiol or testosterone level in Japanese women.

Association of hair dye use with circulating levels of sex hormones in premenopausal Japanese women.

BACKGROUND: Substances identified as animal carcinogens are no longer used as ingredients of hair dyes. However, hair dyes are diverse groups of chemicals, and certain compounds may affect endogenous sex hormone levels. We examined the association between hair dye use and sex hormone levels among premenopausal women. METHODS: Study subjects were 431 premenopausal Japanese women who had regular menstrual cycles less than 40 days long. Information on the use of hair dyes or hair bleach, the type of hair coloring used, the duration of use and the frequency of application was collected using a self-administered questionnaire. Fasting plasma samples were obtained to measure estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone and luteinizing hormone. RESULTS: After controlling for covariates, the mean plasma total testosterone level was about 14% higher in women who had used hair dyes for 10 or more years than that among women who had never used them (P for trend = 0.02). A similar association was observed when the type of hair dye was restricted to permanent hair dyes. A higher frequency of applying non-permanent hair dyes was marginally significantly associated with higher total and free estradiol levels. CONCLUSIONS: Data suggest that long-term use of hair dyes may be associated with an increase in circulating testosterone levels. As this is, to our knowledge, the first study examining the association between hair dye use and sex hormone levels, replication of the results is required.

Associations of acrylamide intake with circulating levels of sex hormones and prolactin in premenopausal Japanese women.

BACKGROUND: It has been hypothesized that alteration of hormone systems is involved in the carcinogenesis of acrylamide. The aim of the present study was to examine the cross-sectional associations between dietary acrylamide intake and sex hormone levels in premenopausal Japanese women. METHODS: Study subjects were 393 women who had regular menstrual cycles less than 40 days long. Acrylamide intake was assessed with a food-frequency questionnaire and was based on acrylamide concentration reported from analyses of Japanese foods. We measured the plasma concentrations of estradiol, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, follicle-stimulating hormone, luteinizing hormone, and prolactin. RESULTS: After controlling for age, the phase of the menstrual cycle, and other covariates, acrylamide intake was statistically significantly inversely associated with total and free estradiol levels and statistically significantly positively associated with follicle-stimulating hormone level. Total and free estradiol levels were 18.2% and 19.3% lower, respectively, in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. Follicle-stimulating hormone levels were 23.5% higher in women in the highest quartile of acrylamide intake than in those in the lowest quartile of intake. CONCLUSION: The data suggest that acrylamide intake may alter estradiol and follicle-stimulating hormone levels. IMPACT: High estradiol levels have been associated with an increased risk of breast cancer. Although the results need confirmation, they highlight the need to investigate the relationships among dietary acrylamide, sex hormones, and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(1); 249-54. ©2014 AACR.

Association of cigarette smoking with skin colour in Japanese women.

OBJECTIVES: Having a lighter skin tone is highly valued among many Asian women. If skin colour is affected by smoking, women may be motivated to avoid tobacco or quit smoking. The present study examined the association of tobacco smoking with skin colour in Japanese women. METHOD: Information on smoking habits was obtained through a self-administered questionnaire completed by 939 Japanese women aged 20-74 in Gifu, Japan, during 2003-2006. Skin colour was examined on the inner side of the upper and lower arm and on the forehead using a Mexameter device (a narrow-band reflective spectrophotometer), which expressed results as a melanin index and erythema index. RESULTS: Current smokers had higher melanin indices than never-smokers and former smokers for all measured sites. The number of cigarettes smoked per day, the years of smoking and pack-years were significantly positively associated with melanin indices for all measured sites after adjustments for age, body mass index, lifetime sun exposure, and room temperature and humidity. Smoking was also significantly associated with erythema indices on the inner upper and lower arms. CONCLUSIONS: These data suggest that smoking is associated with a darker skin colour. If our findings are confirmed by further studies, they could be used in antismoking campaigns or by smoking cessation services.

Plasma amino acid profiles are associated with biomarkers of breast cancer risk in premenopausal Japanese women.

OBJECTIVE: Recently, profiles of plasma amino acids have been utilized to detect diseases including breast cancer. However, there is a possibility that the amino acid status may be associated with the risk of breast cancer. We investigated the relationship of plasma levels of amino acids with levels of sex hormones and insulin-like growth factor (IGF)-1, which are relevant to the etiology of premenopausal breast cancer, in normal premenopausal women. METHODS: Participants were 350 Japanese women who had regular menstrual cycles less than 40-day long. Fasting plasma samples were assayed for estradiol, testosterone, dehydroepiandrosterone sulfate, sex-hormone-binding globulin (SHBG), and IGF-1. A total of 20 amino acids in plasma were quantified by liquid chromatography-mass spectrometry. Information on lifestyle and reproductive factors was obtained using a self-administered questionnaire. RESULTS: The plasma arginine level was significantly inversely correlated with plasma levels of total and free estradiol and IGF-1 after adjusting for age, body mass index, and phase of the menstrual cycle. Plasma leucine and tyrosine levels were significantly positively correlated with the free testosterone level. The ratio of plasma asparagine to the total amino acids was significantly positively correlated with SHBG level. CONCLUSIONS: Plasma levels of some specific amino acids, such as arginine, leucine, tyrosine, and asparagine, were associated with the levels of sex hormones, SHBG, or IGF-1 in premenopausal women. However, the present cross-sectional study cannot provide a cause-effect relation. The implication of amino acids in the etiology of breast cancer needs to be addressed in future studies.

Longer HSD11B2 CA-repeat in impaired glucose tolerance and type 2 diabetes.

Type 2 11ß-hydroxysteroid dehydrogenase encoded by the HSD11B2 gene converts cortisol to inactive cortisone, and alteration in this enzymatic activity might affect glucose homeostasis by affecting circulating levels or tissue availability of glucocorticoids. We investigated the association of HSD11B2 variant with glucose homeostasis. Subjects with normal glucose tolerance (n=585), impaired glucose tolerance (n=202) and type 2 diabetes (n=355) were genotyped for a highly polymorphic CA-repeat polymorphism in the first intron of HSD11B2. Allele and genotype frequencies differed between normal and impaired glucose tolerance (P = 0.0014 and 0.0407, respectively; 4 degree of freedom) or type 2 diabetes (P = 0.0053 and 0.0078), with significant linear trends between the repeat length and the phenotype fraction. In normal subjects, total CA-repeat length was negatively correlated with fasting insulin and HOMA-ß. Thus, subjects having more CA repeats are susceptible to developing abnormal glucose tolerance, whereas normal subjects carrying more CA repeats appeared to have frugal characteristics in insulin secretion.

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome.

AIM: To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease (NAFLD). METHODS: Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography. This study involved 11 714 apparently healthy Japanese men and women, 18 to 83 years of age. NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d, known liver disease, or current use of medication. The revised criteria of the National Cholesterol Education Program Adult Treatment Panel III were used to characterize the metabolic syndrome. RESULTS: NAFLD was detected in 32.2% (95% CI: 31.0%-33.5%) of men (n = 1874 of 5811) and in 8.7% (95% CI: 8.0%-9.5%) of women (n = 514 of 5903). Among obese people, the prevalence of NAFLD was as high as 67.3% (95% CI: 64.8%-69.7%) in men and 45.8% (95% CI: 41.7%-50.0%) in women. Although NAFLD was thought of as being the liver phenotype of metabolic syndrome, the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women. 66.8% of men and 70.4% of women with NAFLD were not diagnosed with the metabolic syndrome. 48.2% of men with NAFLD and 49.8% of women with NAFLD weren't overweight [body mass index (BMI) ≥ 25 kg/m(2)]. In the same way, 68.6% of men with NAFLD and 37.9% of women with NAFLD weren't satisfied with abdominal classification (≥ 90 cm for men and ≥ 80 cm for women). Next, authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome. The sensitivity of the definition "at least 1 criterion" was as good as 84.8% in men and 86.6% in women. Separating subjects by BMI, the sensitivity was higher in obese men and women than in non-obese men and women (92.3% vs 76.8% in men, 96.1% vs 77.0% in women, respectively). CONCLUSION: Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women.

OBJECTIVE: Endogenous sex hormones have been implicated in the etiology of breast cancer. Dietary factors such as fat, dietary fiber, soy isoflavones, and alcohol have been suggested to influence endogenous estrogen and other steroid hormone levels. We examined the relationship among these dietary factors and plasma sex hormone levels in premenopausal Japanese women. METHODS: We measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin, a follicle-stimulating hormone, a luteinizing hormone, and prolactin among 393 premenopausal women who had regular menstrual cycles fewer than 40 days apart. The dietary intakes were estimated with a validated food frequency questionnaire. RESULTS: After controlling for age, BMI, phase of the menstrual cycle, number of births, age at first birth, history of breastfeeding, and smoking status, the saturated fat intake was significantly positively associated with total estradiol and free estradiol levels. Intakes of the other types of fat, dietary fiber, soy isoflavones, and alcohol were not significantly associated with levels of any hormone measured. CONCLUSIONS: These data suggest that a high intake of saturated fat is associated with increased estradiol levels in premenopausal Japanese women. Saturated fat intake may have implications in the etiology of breast cancer.

Aging is a risk factor of nonalcoholic fatty liver disease in premenopausal women.

AIM: To clarify the relationship between age, menopause, and nonalcoholic fatty liver disease (NAFLD) in women. METHODS: We conducted a follow-up study on nonalcoholic fatty liver disease by using abdominal ultrasonography, and investigated the relationship of age and menopause with the development of NAFLD in women. We followed 1829 women and 2572 men (response rate, 86%) selected in 2001 to represent the non-institutionalized adult population of Gifu, Japan. Data collected included self-reported medical history, lifestyle factors, and menopausal status. The postmenopausal state was defined as beginning 1 year after the cessation of menses. We diagnosed NAFLD with the aid of abdominal ultrasonography by using diagnostic criteria described previously. RESULTS: The prevalence of NAFLD in women increases with age, but does not alter with age in men. Furthermore, the prevalence of NAFLD in premenopausal women (6%) was lower than that in men (24%) and in postmenopausal women (15%). The associations of the postmenopausal state and hormone replacement therapy with NAFLD were statistically significant in a univariate logistic regression model. At the follow-up examination, 67 women (5%) were newly diagnosed with NAFLD. The incidence of NAFLD was 3.5% (28/802) in premenopausal women, 7.5% (4/53) in menopausal women, 6.1% (24/392) in postmenopausal women, and 5.3% (11/206) in women receiving hormone replacement therapy. The weight gain in premenopausal women was equal to that in postmenopausal women. Metabolic syndrome and weight gain were independent risk factors for NAFLD in pre- and postmenopausal women, but age was an independent risk factor in premenopausal women only. CONCLUSION: Aging is a risk factor for NAFLD in premenopausal women, independent of weight gain or influence of metabolic syndrome.

Protective effect of alcohol consumption for fatty liver but not metabolic syndrome.

AIM: To investigate the effect of alcohol on the metabolic syndrome (MS) and fatty liver in Japanese men and women. METHODS: A cross-sectional study was conducted in a medical health checkup program at a general hospital. This study involved 18 571 Japanese men and women, 18-88 years of age, with a mean body mass index of 22.6 kg/m(2). A standardized questionnaire was administered. The total amount of alcohol consumed per week was calculated, and categorized into four grades. Fatty liver was examined by ultrasound modified criteria of the revised National Cholesterol Education Program Adult Treatment Panel III and the new International Diabetes Federation. RESULTS: The prevalence of fatty liver decreased in men and women with light to moderate alcohol consumption, whereas the prevalence of MS was not so changed. The prevalence of fatty liver of any grade in men was lower than that in those with no or minimal alcohol consumption. In women with light to moderate alcohol consumption, prevalence of fatty liver was lower than that in women with no or minimal alcohol consumption. By logistic regression analysis, the odds ratio (OR) for MS in women with light alcohol consumption was decreased to < 1.0, but this change was not clear in men. The OR for fatty liver was clearly < 1.0 in men with any level of alcohol consumption and in women with light to moderate consumption. CONCLUSION: Light to moderate alcohol consumption has a favorable effect for fatty liver, but not for MS in Japanese men and women.

Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women.

Melatonin's potential preventive effect against cardiovascular disease (CVD) remains hypothetical. No study has evaluated the relationships between endogenous melatonin and the established blood biomarkers related to CVD. The objective of the present study is to examine the association between the endogenous melatonin level and various established blood biomarkers of risk of CVD, including white blood cell (WBC) count and plasma concentrations of lipids, homocysteine, uric acid (UA), and high-sensitivity C-reactive protein (hs-CRP). This cross-sectional study included 181 Japanese women who attended a health checkup program provided by a general hospital between March 2005 and March 2006. All study subjects responded to a self-administered questionnaire and were measured for weight, height, and blood pressure. Venous fasting blood and first-void morning urine were obtained from all subjects. Statistically significant inverse correlations were observed between urinary 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin in urine, and WBC count, UA, and hs-CRP after controlling for age, body mass index, menopausal status, smoking status, diet, sleeping habits, and exercise (r = -0.19, -0.21, and -0.24, respectively). There were no significant correlations between urinary aMT6s and plasma lipids and homocysteine. These data suggested that the urinary aMT6s level was inversely associated with established independent risk factors for CVD, such as WBC, UA, and hs-CRP. Endogenous melatonin may have implications for the risk of CVD.

Characteristics of chronic fatigue syndrome in a Japanese community population : chronic fatigue syndrome in Japan.

This study seeks to estimate the prevalence of chronic fatigue syndrome (CFS) and assess the characteristics of CFS in a community population in Japan using laboratory tests and questionnaires for lifestyle, fatigue states, and depression states. The design of this study is a cross-sectional observational study. The setting of this study is a medical health checkup program in a general hospital. This study was conducted with 1,430 Japanese (867 men and 563 women), 20 to 78 years of age. We classified participants who complained of fatigue according to the case definition of CFS proposed by the Centers for Disease Control and Prevention in the USA in 1994. Alcohol, caffeine, catechin and total polyphenol consumption, smoking status, sleep duration, and physical activity were evaluated using questionnaires. The prevalence of CFS was 1.0% (95% CI 0.5-1.6%) of a community population in Japan. Although various lifestyle factors of the participants with CFS were similar to those without chronic fatigue, average sleep duration was significantly shorter among the participants with CFS (5.5 ± 0.8 h) compared to those without chronic fatigue (6.3 ± 0.9 h, P < 0.001). Proportion at subjects having average sleep duration of less than 6 h was 64.3% among the participants with CFS in contrast to only 15.0% in those without chronic fatigue (P < 0.001). Among the eight case-defining symptoms, "Unrefreshing sleep" had high sensitivity and high specificity for screening CFS in Japanese population (92.9% and 87.8%, respectively). The average sleep duration was notably shorter in Japanese suffering from CFS. Further longitudinal study is needed to evaluate the possibility of extreme short sleep duration as a major cause of CFS in Japan.

Associations of body size and reproductive factors with circulating levels of sex hormones and prolactin in premenopausal Japanese women.

OBJECTIVE: Body size and reproductive factors are important risk factors of breast cancer. The aim of the present study was to examine the associations of these factors with blood concentrations of sex hormones and prolactin in premenopausal Japanese women. METHODS: We measured the plasma concentrations of estradiol, estrone, testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), follicle-stimulating hormone, luteinizing hormone, and prolactin among 436 women who had regular menstrual cycles less than 40 days long. Information on menstrual and reproductive factors including history of breastfeeding was obtained using a self-administered questionnaire. Height and weight were measured. RESULTS: After controlling for age and the phase of the menstrual cycle, the body mass index (BMI) was significantly inversely associated with total estradiol, estrone and SHBG and significantly positively associated with total and free testosterone and DHEAS. Nulliparous women had significantly higher levels of total and free testosterone, DHEAS, and prolactin than parous women. Duration of breastfeeding for the first child was significantly inversely associated with free testosterone and prolactin levels. CONCLUSIONS: The data suggest that an increased risk of premenopausal breast cancer associated with low BMI is partially mediated by an increased total estradiol. Androgens and prolactin may explain the breast cancer protection provided by giving birth and breastfeeding.

Lifestyle and health factors associated with stress urinary incontinence in Japanese women.

OBJECTIVES: Studies focusing on lifestyle and health factors and stress urinary incontinence (SUI) are scarce in Japan. The aim of this study is to examine the association of lifestyle and health factors in SUI. METHODS: Study subjects were retrieved from Japanese women participating in a health checkup program provided by a general hospital between October 2003 and March 2006. The presence of SUI was confirmed by responses to a self-administered questionnaire assessing lower urinary tract symptoms. The questionnaire included other questions on lifestyle and health factors. Each subject underwent weight and height measurements. RESULTS: A total of 823 women completed the questionnaire and were included in the analyses (the response rate was 62.6%). Of them, 70 (8.5%) women had SUI. BMI and parity were significantly positively associated with SUI (OR=3.47 and 7.17, 95% CI 1.65-7.33 and 1.71-30.04, respectively). Multiple logistic regression analysis controlling for age, parity, and BMI showed that first delivery at age >27 (OR=1.82, 95% CI 0.97-3.41), past estrogen use (OR=2.50, 95% CI 1.14-5.47), and unilateral ovariectomy (OR=3.07, 95% CI 1.16-8.13) were also significantly associated with SUI. CONCLUSIONS: The data suggested that lifestyle and health factors such as parity, BMI, age at first delivery, past estrogen use, and unilateral ovariectomy were associated with SUI in Japanese women.

Association of dietary fat, vegetables and antioxidant micronutrients with skin ageing in Japanese women.

Daily diet may have implications for skin ageing. However, data on the relationship between diet and the parameters of skin conditions are scarce. The present study aimed to examine the associations of biophysical properties of the skin of women with intakes of fats and antioxidant micronutrients as well as food groups as sources of these nutrients. In a cross-sectional study, we measured the hydration, surface lipids and elasticity of the skin of 716 Japanese women using non-invasive techniques. The extent of facial wrinkles in the crow's-foot area was determined by observation using the Daniell scale. Each subject's usual diet was determined with the use of a validated FFQ. After controlling for covariates including age, smoking status, BMI and lifetime sun exposure, the results showed that higher intakes of total fat, saturated fat and monounsaturated fat were significantly associated with increased skin elasticity. A higher intake of green and yellow vegetables was significantly associated with a decreased Daniell wrinkling score. Intake of saturated fat was significantly inversely associated with the Daniell wrinkling score after additional adjustment for green and yellow vegetable intake. Further studies with more accurate measurement methods are needed to investigate the role of daily diet in skin ageing.

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 subject's 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.

The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is closely associated with the metabolic syndrome. AIM: We evaluated the association among the metabolic syndrome, visceral fat accumulation, and the severity of fatty liver with a new scoring system of ultrasonographic findings in apparently healthy Japanese adults. METHODS: Subjects consisted of 94 patients who received liver biopsy and 4,826 participants who were selected from the general population. Two hepatologists scored the ultrasonographic findings from 0 to 6 points. We calculated Cohen's kappa of within-observer reliability and between-observer reliability. We evaluated the predictive value of the score by the area under a conventional receiver operating characteristic curve (AUC). RESULTS: Within-observer reliability was 0.95 (95% CI 0.93-0.97, P<0.001) and between-observer reliability was 0.95 (95% CI 0.93-0.97, P<0.001). The AUC to diagnose NAFLD was 0.980. The sensitivity was 91.7% (95% CI 87.0-95.1, P<0.001) and the specificity was 100% (95% CI 95.4-100.0, P<0.001). The AUC to diagnose visceral obesity was 0.821. The sensitivity was 68.3% (95% CI 51.9-81.9, P=0.028) and the specificity was 95.1% (95% CI 86.3-99.0, P<0.001). Adjusted odds ratio of the score for the metabolic syndrome was 1.37 (95% CI 1.26-1.49, P<0.001). CONCLUSIONS: The scoring system with abdominal ultrasonography could provide accurate information about hepatic steatosis, visceral obesity, and the metabolic syndrome in apparently healthy people who do not consume alcohol.

Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease.

AIM: To clarify whether nonalcoholic fatty liver disease (NAFLD) increases the risk of cardiovascular disease. METHODS: We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program. NAFLD was diagnosed by abdominal ultrasonography. The metabolic syndrome (MS) was defined according to the modified National Cholesterol Education Program (NCEP) ATP III criteria. Five years after the baseline evaluations, the incidence of cardiovascular disease was assessed by a self-administered questionnaire. RESULTS: Among 1221 participants available for outcome analyses, the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline (5 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage) than 990 subjects without NAFLD (3 coronary heart disease, 6 ischemic stroke, and 1 cerebral hemorrhage). Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors (odds ratio 4.12, 95% CI, 1.58 to 10.75, P = 0.004). MS was also independently associated with cardiovascular events. But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease. CONCLUSION: Although both of them were predictors of cardiovascular disease, NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model. NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.