Smoking results in accumulation of ectopic fat in the liver.

OBJECTIVE: An association between smoking and nonalcoholic fatty liver disease has been reported. However, objective quantification of intrahepatic fat via magnetic resonance spectroscopy (MRS) in relation to smoking has rarely been performed in previous studies. Moreover, the possible pathways via which smoking could induce ectopic fat accumulation have not yet been addressed. The current study aimed to examine the association between smoking status and intrahepatic fat quantity and explore the possible mediating effects of triglycerides (TG) and adiponectin. SUBJECTS AND METHODS: Magnetic resonance imager (MRI) spectra were analyzed to quantify intrahepatic fat in 45 men who were on average 62.3 years of age. Smoking status and alcohol intake were self-reported. Accelerometers were used to record daily total physical activity. Fasting blood TG and adiponectin levels were measured enzymatically. Differences in mean intrahepatic fat values according to smoking status were assessed using analysis of covariance. RESULTS: A stepwise increase in mean intrahepatic fat was observed between never, former, and current smokers, respectively, independent of age, physical activity, alcohol intake, and body mass index (BMI) (P=0.005). Adjustment for TG and adiponectin significantly attenuated this association (P=0.074). CONCLUSION: Current smoking was significantly associated with increased intrahepatic fat, which may be a result of adipocyte dysfunction, manifested as high circulating TG concentrations and low adiponectin levels.

Independent association of liver fat accumulation with insulin resistance.

BACKGROUND: To examine the association of intrahepatic fat with homeostasis model assessment-insulin resistance (HOMA-IR), a marker of insulin resistance, in Japanese adults, and whether intrahepatic fat is associated with insulin resistance independent of waist circumference and other measures of obesity. METHODS: Fifty-three individuals aged 37-69 were studied. Spectrum obtained using a 3-T magnetic resonance imager was analysed with LCModel to quantify intrahepatic fat. Blood levels of insulin, glucose and other biochemical markers were obtained after 8h or more fasting. Percent body fat was estimated by a bioelectrical impedance analyzer. HOMA-IR and intrahepatic fat content were log-transformed in the analysis. RESULTS: We found a positive correlation between intrahepatic fat and HOMA-IR, which was independent of the anthropometric measures of obesity. In contrast, significant and positive correlations of body mass index, percent body fat, and waist circumference with HOMA-IR were largely explained by their associations with intrahepatic fat. Intrahepatic fat was positively associated with alanine transaminase and triglycerides even after adjustment for HOMA-IR. CONCLUSION: Intrahepatic fat was associated with insulin resistance independent of age, sex, and measures of obesity in Japanese adults. Hypertriglyceridemia and liver injury may directly occur subsequent to intrahepatic fat accumulation.

Higher dietary intake of alpha-linolenic acid is associated with lower insulin resistance in middle-aged Japanese.

OBJECTIVE: To investigate the associations between dietary intake of n-3 polyunsaturated fatty acids (plant-derived alpha-linolenic acid: ALA, and marine-derived eicosapentaenoic and docosahexaenoic acid: EPA+DHA) and insulin resistance (IR) in a lean population with high n-3 PUFA intake. METHOD: We cross-sectionally studied 3383 Japanese local government workers aged 35-66 in 2002. IR was defined as the highest quartile of homeostasis model assessment, and nutrient intake was estimated from a diet history questionnaire. The odds ratios (ORs) of IR taking the lowest quartile of ALA or EPA+DHA intake as the reference were calculated by logistic regression analysis. RESULTS: Mean age, body mass index (BMI), and dietary ALA, and median of dietary EPA+DHA were 47.9 years, 22.9 kg/m(2), and 1.90 g/day (0.88%E) and 0.77 g/day (0.36%E), respectively. The ORs of IR decreased across the quartiles of ALA intake (multivariate-adjusted OR for Q4 versus Q1=0.74, P for trend=0.01) and the association was observed only in subjects with a BMI of <25 kg/m(2) (P for interaction=0.033). However EPA+DHA showed no such associations consistently. CONCLUSION: Higher ALA intake was significantly associated with a lower prevalence of IR in normal weight individuals of middle-aged Japanese men and women.

Changes in activities of daily living, physical fitness, and depressive symptoms after six-month periodic well-rounded exercise programs for older adults living in nursing homes or special nursing facilities.

A 6-month, twice weekly, well-rounded exercise program (47 sessions in total) comprised of a combination of aerobic, resistance and flexibility training was provided for institutionalized older adults aged 60 to 93. We analyzed the data of 18 older adults who could stand and had attended more than 10% of the classes (mean participation rate: 54%) to examine changes in activities of daily living (ADL), physical fitness tests and depressive moods. The mean (+/- standard deviation, range) age of the participants was 71.3 (+/- 15.6, 60-93) in men and 85.9 (+/- 5.8, 72-93) in women. Significant improvement in ADL of the hand manipulation domain and borderline significant improvement in ADL of the mobility domain were observed (McNemar test p = 0.011 and 0.072, respectively). A 6-minute walk distance increased significantly from 151.6 m to 236.6 m (p = 0.01, paired t-test), and the result of the Soda Pop test, which tests hand-eye coordination, also improved significantly from 35.2 sec to 25.3 sec (p = 0.01, paired t-test). These findings suggest that such a program could be effective in improving the ADL and physical fitness of the elderly.

Uric acid and left ventricular hypertrophy in Japanese men.

BACKGROUND: Experimental studies have reported that allopurinol protects hypertensive rats from left ventricular hypertrophy (LVH) with negligible effects on blood pressure (BP). Uric acid (UA) was thought to induce cardiomyocyte growth and interstitial fibrosis of the heart, partly via activation of the renin-angiotensin system. In the present study, the relationship between serum UA levels and electrocardiographically-diagnosed LVH (ECG-LVH) was examined in Japanese men not taking medication for hypertension (HTN), which could confound the association. METHODS AND RESULTS: A total of 3,305 male workers aged 35-66 years (mean age+/-SD, 48.0+/-7.1) were studied. LVH was defined as meeting the ECG criteria (ie, Sokolow-Lyon voltage and/or Cornell voltage QRS duration product). Subjects were divided into 3 groups by tertile of serum UA level. The highest tertile (UA range 0.39-0.65 mmol/L or 6.6-11.0 mg/dl) had a significantly increased prevalence of LVH compared with the lowest tertile independent of age, body mass index, serum creatinine level, HTN, diabetes and hyperlipidemia (odds ratio 1.58, 95% confidence interval 1.23-2.02, P<0.001). Similar results were obtained in both the normal and high BP subgroups. CONCLUSIONS: UA concentration independently and positively associated with ECG-LVH in Japanese men.

Self-reported medical history was generally accurate among Japanese workplace population.

OBJECTIVE: To assess the validity of self-reported medical history of several diseases among the Japanese population, and to clarify to what extent the self-reported year of diagnosis for chronic diseases is different from the physician's reports. STUDY DESIGN AND SETTING: Subjects were 8,947 persons who responded to questions about medical history in a self-administered questionnaire. Of them, 854 subjects reported one or more medical histories and gave permission to contact their physician. The physicians were then requested to provide information on 809 subjects. Valid responses of 714 subjects were collected. We compared the self-reported medical histories with those reported by the physician. RESULTS: Of 15 persons who reported myocardial infarction, 13 (87%) were confirmed. Angina pectoris was verified in eight out of the 11 (73%). The confirmation proportions of hypertension, diabetes, hyperlipidemia, and hyperuricemia were 97%, 96%, 95%, and 95%, respectively. The self-reported year of diagnosis was 1.70-2.49 years earlier than the physician-reported year for chronic diseases. Agreement between the self-reported and the physician-reported years was higher, the more recent the self-reported year was. CONCLUSION: Self-reported medical histories were generally accurate, especially for diseases with clear diagnostic criteria. However, investigators should be aware of the errors in reporting the year of diagnosis.

Having more healthy practice was associated with low white blood cell counts in middle-aged Japanese male and female workers.

White blood cell (WBC) count is well known to be an independent risk marker for cardiovascular disease. The aim of this study is to examine the relationships of WBC counts to seven health practices including obesity, eating habits, smoking, alcohol intake, sleeping, physical activity, and perceived mental stress, and then clustering the relevant healthy practices. The subjects were 1,492 male and 316 female Japanese workers aged 40 yr and over in 2002. Each of seven health practices from a self-administered questionnaire was categorized as a 'healthy' or 'unhealthy' practice, and WBC counts from fasting blood samples were determined by automated particle counters. The means of age and WBC counts were 49.5 yr and 5,375 cells/microl in men, and 48.6 yr and 4,890 cells/microl in women, respectively. After multivariate adjustments for all health practices and age, the estimated WBC counts were significantly lower in normal weight subjects and never or former smokers (p<0.01). Age-adjusted WBC counts decreased significantly by 204.9+/-23.7 cells/microl (means+/-SE) and 117.6+/-53.2 cells/microl for each increase in one healthy practice (p<0.05), respectively, suggesting that cultivating healthier practices would lead to lower WBC counts. This study recommends modifying unhealthy practice one by one and maintaining healthy practices as an effective strategy for the prevention of atherosclerotic diseases, in addition, to quit smoking or abstain from heavy smoking especially in men is important to prevent the low-grade inflammation.

Low leptin but high insulin resistance of smokers in Japanese men.

AIMS: To investigate the association between smoking and leptin, and to discuss their influence on diabetes in a large-scale study of Japanese men. METHODS: A cross-sectional study was carried out in 2002. The subjects were 2836 men aged 35-66. Smoking history was investigated in a self-administered questionnaire. Blood leptin, glucose and insulin were measured. RESULTS: Significant differences in leptin levels and homeostasis model assessment of insulin resistance (HOMA-IR) related to smoking status were observed (P=0.001 and P=0.008, respectively). The multivariate-adjusted geometric means of leptin in current, past and never smokers were 3.88, 4.08 and 4.12 ng/ml, respectively, while the means of HOMA-IR were 1.64, 1.61 and 1.49, respectively. The age-, body mass index-, and other lifestyle-adjusted prevalences of diabetes in current and never smokers were 9.2 and 4.7%, respectively. That of current smokers was significantly higher than in never smokers (P<0.001). The dose-dependent association found between the intensity of smoking and leptin levels in current smokers was statistically significant (P=0.030). CONCLUSIONS: The present finding may explain in part an association among smoking, leptin levels and diabetes. Smoking is one of the important modifiable risk factors for the prevention of diabetes.

Contribution of adipocytokines to low-grade inflammatory state as expressed by circulating C-reactive protein in Japanese men: comparison of leptin and adiponectin.

BACKGROUND: Circulating C-reactive protein (CRP) is a marker of inflammation and is associated with the incidence of cardiovascular events. Although it has been known that adiponectin protects, whereas leptin accelerates, the development of atherosclerotic diseases, the comparative strength of their reciprocal effects on circulating CRP remains unclear. METHODS: We studied a population of 2049 Japanese men aged 35 to 66. For all subjects, multiple regression analysis performed with log-transformed CRP concentration as the dependent variable, and with log-transformed leptin, log-transformed adiponectin, age, BMI, smoking status, and components of metabolic syndrome as independent variables. RESULTS: Both leptin (positively) and adiponectin (negatively) were significantly and independently associated with CRP concentration. The absolute value of the standardized regression coefficient (st-beta) of leptin (st-beta=0.201) was higher than that of adiponectin (st-beta=-0.082). After subjects were stratified by current BMI level, both of the adipocytokines were significantly associated with CRP concentration among subjects with BMI <25 kg/m(2), whereas only leptin was significantly associated with CRP concentration among subjects with BMI >=25 kg/m(2). CONCLUSIONS: Both leptin and adiponectin were independently associated with CRP concentration. Leptin was more strongly related to CRP levels than adiponectin was, especially among obese subjects.

Association between low birth weight and elevated white blood cell count in adulthood within a Japanese population.

BACKGROUND: Epidemiological studies have demonstrated the association between low birth weight and increased adulthood risk for cardiovascular and metabolic diseases. However, the precise mechanism underlying the association remains poorly understood. We investigated the association between birth weight and adult white blood cell (WBC) count in a Japanese population. METHODS AND RESULTS: The subjects were 779 men and 209 women aged 35-64 years. The mean WBC count was 5,283 /microl (SD: 1,326). Birth weight was divided to 6 categories: <2,500, 2,500-<2,800, 2,800-<3,000, 3,000-<3,200, 3,200-<3,500, and >3,500 g. Estimated WBC counts were 5,729, 5,341, 5,301, 5,212, 5,013 and 5,372 for the subjects with birth weights of the above respective categories (p=0.015, trend p=0.016) by one-way analysis of covariance after adjustments for sex, age, height, body mass index (BMI), lifestyles, and chronic diseases. This association was pronounced among the subjects with a BMI <25.0 kg/m2 rather than those with a higher BMI. CONCLUSIONS: These findings support the idea that part of the association of low birth weight with elevated risk for vascular and metabolic diseases in later life could be mediated by an inflammatory pathway.

Further inflammatory information on metabolic syndrome by adiponectin evaluation.

BACKGROUND: Despite a close association of adiponectin with metabolic syndrome (MetS), its usefulness as an additional MetS factor has not been well investigated. METHODS: We studied 2327 apparently healthy Japanese male office workers aged 35 to 66 years old and investigated cross-sectionally whether categorization by serum adiponectin distinguished participants' levels of high-sensitivity C-reactive protein (CRP) beyond the conventional MetS. RESULTS: In a linear regression analysis, adiponectin was associated with CRP independently of all MetS factors (beta=-0.192, P<0.001). Furthermore, a graded decrease in CRP level was observed with elevation of adiponectin in every stratum characterized by the presence or absence of each MetS component (trend P<0.05 in all strata except those of decreased high-density lipoprotein cholesterol or hyperglycemia). Similarly, geometric means of CRP levels (mg/l) decreased as adiponectin increased from the lowest to the highest tertile in all strata classified by the number of MetS components, though a P value did not reach statistical significance in those with 3 MetS components (the stratum of 0 MetS component: 0.41 [95% confidence interval, 0.34-0.49], 0.32 [0.28-0.37] and 0.26 [0.23-0.30], trend P<0.001; 1 component: 0.45 [0.39-0.52], 0.38 [0.34-0.43], and 0.32 [0.28-0.36], trend P<0.001; 2 components: 0.58 [0.50-0.67], 0.51 [0.44-0.60], and 0.46 [0.38-0.55], trend P=0.043; 3 components: 0.80 [0.66-0.96], 0.69 [0.55-0.87], and 0.58 [0.39-0.85], trend P=0.139). CONCLUSIONS: Adiponectin evaluation provides additional inflammatory information on conventional MetS, supporting the potential of hypoadiponectinemia as an additional MetS component for identifying high-risk individuals for cardiovascular disease.

Eating fast leads to insulin resistance: findings in middle-aged Japanese men and women.

OBJECTIVE: To examine relationships between speed of eating and insulin resistance. METHODS: Cross-sectional study of 2704 male (mean age and BMI: 48.2 y and 23.3 kg/m(2)) and 761 female (46.3 y and 21.8 kg/m(2)) non-diabetic Japanese civil servants, 75% clerical, and 25% manual laborers, using a two-part questionnaire on life-style factors and diet history with self-assessment of categorical speed of eating and energy intake over a 1-month period. We measured BMI, blood glucose and insulin concentrations and calculated insulin resistance using the homeostasis model assessment of insulin resistance: (HOMA-IR). RESULTS: BMI correlated with eating rate in both sexes, and with daily energy intake in men. Multiple regression analysis of log HOMA-IR by categorical speed of eating, adjusting for age, energy intake and lifestyle factors showed a statistically significant gradual increase in HOMA-IR with increases in relative eating rate in men (p<0.001, for trend) and in women (p<0.01). Adjusting for BMI, this positive relationship appeared only in men (p=0.03). CONCLUSIONS: Our results suggest that eating fast is independently associated with insulin resistance in middle-aged Japanese men and women.

Smoking status and adiponectin in healthy Japanese men and women.

BACKGROUND: Recent studies promisingly indicate that adiponectin plays an important and fundamental role in the development and progression of metabolic and atherosclerosis disorders. Smoking is known as one of the most important risk factors of atherosclerosis, and its relation with metabolic disorders has also been reported. We therefore investigated the association between cigarette smoking and adiponectin concentration in a large sample of Japanese men and women. METHOD: The cross-sectional study was carried out in 2002. The subjects were 3260 men and 953 women local government workers aged 35 to 59 in Japan. Lifestyle-related variables including detailed smoking history were inquired in a self-administered questionnaire. RESULTS: Significant differences in adiponectin levels related to smoking status were observed in both men and women (p=0.001). A dose-dependent association was found between the intensity of smoking and adiponectin levels in current smokers, and was statistically significant in men (p for trend=0.006 in the multivariate-adjusted model). Men who quit smoking for more than 20 years and women for more than 10 years had an adiponectin concentration similar to that observed in non-smokers. CONCLUSION: We not only revealed that current smoking habit was associated with low adiponectin level but also found a dose-dependent association between smoking intensity and adiponectin level in current smokers. The present finding may provide further evidence of the importance of a causal relationship between smoking status and adiponectin concentrations.

High-sensitivity C-reactive protein is quite low in Japanese men at high coronary risk.

BACKGROUND: Although numerous studies have demonstrated a positive association of high-sensitivity C-reactive protein (CRP) with the incidence of coronary heart disease (CHD), little information exists regarding this issue in Japanese. METHODS AND RESULTS: The association between CRP and the Framingham Risk Score (FRS) was investigated in 2,523 middle-aged Japanese men without a medical history of CHD. CRP was significantly associated with this score obtained from all FRS factors. After dividing subjects into 4 categories of relative risk estimate for CHD, the geometric mean of CRP (mg/L) increased gradually with the CHD risk (below average: 0.39 [95% confidence interval, 0.37-0.41], average: 0.58 [0.50-0.67], moderately above average: 0.70 [0.57-0.86], high: 0.79 [0.58-1.09], trend p<0.001). However, it should be noted that the mean CRP concentration of the high-risk group was only 0.79 mg/L and a greater proportion (63.8%) of the high-risk subjects was in the low-risk range of CRP (<1 mg/L). CONCLUSIONS: Circulating CRP well reflect the estimated CHD risk, indicating that CRP may be useful for coronary risk stratification in Japanese also. However, the details of the CRP level in Japanese must be investigated further by prospective studies to determine the Japanese-specific cutoff points for CHD risk evaluation.

Adiponectin level and left ventricular hypertrophy in Japanese men.

A recent study has demonstrated that adiponectin inhibited hypertrophic signaling in the myocardium of mice, implying that a decrease in the blood adiponectin level could cause cardiac muscle hypertrophy. We hypothesized that a relationship might exist between the serum adiponectin level and electrocardiographically diagnosed left ventricular hypertrophy (ECG-LVH), and we examined this hypothesis by epidemiological study of 2839 Japanese male workers who were not taking medications for hypertension. ECG-LVH was defined as meeting Sokolow-Lyon voltage criteria and/or Cornell voltage-duration product. The subjects were categorized by tertiles of serum adiponectin level, and a multivariate logistic regression analysis was conducted relating left ventricular hypertrophy to adiponectin tertiles adjusting for potential confounding factors. Prevalence of ECG-LVH in the studied sample was 16.7%. Adiponectin ranged from 1.0 to 5.0 microg/mL in the lowest category and from 7.4 to 30.6 microg/mL in the highest. Compared with subjects in the highest adiponectin category, those in the lowest one had a significantly higher prevalence of ECG-LVH independent of age, body mass index, and systolic blood pressure with an odds ratio of 1.50 and a 95% CI of 1.16 to 1.94. Further adjustment for high-density lipoprotein cholesterol, triglyceride, and insulin resistance did not change the association (odds ratio: 1.68; 95% CI: 1.28 to 2.21; P<0.001). Similar results were obtained when different criteria for ECG-LVH were used or when subjects were stratified by blood pressure or body mass index. Adiponectin concentration was inversely and independently associated with ECG-LVH in Japanese men.

The transition to menopause reinforces adiponectin production and its contribution to improvement of insulin-resistant state.

OBJECTIVE: To evaluate the influence of menopausal status on the serum adiponectin concentration and investigate whether the contribution of adiponectin to insulin resistance is modified by menopausal status. SUBJECTS: We conducted a population-based, cross-sectional study of 207 premenopausal and 206 postmenopausal Japanese women. MEASUREMENTS: Data on anthropometric characteristics, fasting serum adiponectin, glucose and insulin concentrations were used. Insulin resistance (homeostasis model assessment of insulin resistance: HOMA-IR) was calculated. RESULTS: Postmenopausal women had significantly higher HOMA-IRs than premenopausal women [1.50 (1.42, 1.59) vs 1.18 (1.12, 1.24), geometric mean (1 standard error range), P = 0.005]. Paradoxically, adiponectin levels in postmenopausal women were also significantly higher than those in premenopausal women [10.3 (9.95, 10.7) vs 9.04 (8.71, 9.39), P = 0.028]. Multiple regression analysis showed that body mass index (BMI) was the only significantly independent predictor [standardized partial regression coefficients (sbeta) = 0.319, P < 0.001] for HOMA-IR among premenopausal women, whereas both BMI and adiponectin were the significant predictors among postmenopausal (sbeta = 0.334 and -0.141, P < 0.001 and < 0.05, respectively). When the subjects were restricted to those without metabolic disorders including high blood pressure, hypertriglyceridaemia, hypo-HDL cholesterolaemia and high fasting glucose, adiponectin (sbeta = -0.249, P < 0.05) was the only significant predictor for HOMA-IR among postmenopausal women but BMI was not significant (sbeta = 0.223, P = 0.075). CONCLUSIONS: The transition to menopause increases serum adiponectin concentrations. And the significant and negative association between adiponectin and HOMA-IR was observed only after menopause. Therefore, adiponectin may play a role in the improvement of an incipient insulin-resistant state after, rather than before, menopause.

Birth weight and adult hypertension: cross-sectional study in a Japanese workplace population.

BACKGROUND: Low birth weight has been associated with adult hypertension in several Western populations. This association needs to be evaluated in Japanese people. METHODS AND RESULTS: A population-based cross-sectional study of 3,107 subjects (2,303 males and 804 females) aged 35-66 years was conducted. The participants responded to a questionnaire about their birth weights, blood pressure, medical history, parental history, and lifestyle factors. Hypertension was defined as systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg and/or under treatment by anti-hypertensives. Multiple logistic regression analysis adjusted for age, sex, body mass index, parental history, and lifestyle revealed the adjusted odds ratios for hypertension were 1.26 (95% confidence interval: 0.88-1.80), 1.00 (reference), 0.89 (0.73-1.08) and 0.70 (0.49-1.00) in subjects in birth weight categories of <2,500 g, 2,500-<3,000 g, 3,000-<3,500 g, 3,500- g, respectively (p-value for trend =0.009). Furthermore, this inverse association was clearly pronounced in normal-weight subjects. CONCLUSION: Low birth weight was independently associated with adult hypertension in the Japanese workplace population. Our results support the inverse association observed previously in Western populations and suggest that intrauterine environmental insults might lead to permanent changes in the metabolism and structure of the fetal organs influencing the regulation of blood pressure.