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Plasma free amino acid (PFAA) profile is highlighted in its association with visceral obesity and hyperinsulinemia, and future diabetes. Indeed PFAA profiling potentially can evaluate individuals' future risks of developing lifestyle-related diseases, in addition to diabetes. However, few studies have been performed especially in Asian populations, about the optimal combination of PFAAs for evaluating health risks. We quantified PFAA levels in 3,701 Japanese subjects, and determined visceral fat area (VFA) and two-hour post-challenge insulin (Ins120 min) values in 865 and 1,160 subjects, respectively. Then, models between PFAA levels and the VFA or Ins120 min values were constructed by multiple linear regression analysis with variable selection. Finally, a cohort study of 2,984 subjects to examine capabilities of the obtained models for predicting four-year risk of developing new-onset lifestyle-related diseases was conducted. The correlation coefficients of the obtained PFAA models against VFA or Ins120 min were higher than single PFAA level. Our models work well for future risk prediction. Even after adjusting for commonly accepted multiple risk factors, these models can predict future development of diabetes, metabolic syndrome, and dyslipidemia. PFAA profiles confer independent and differing contributions to increasing the lifestyle-related disease risks in addition to the currently known factors in a general Japanese population.

Introduction: Whether or not metabolic syndrome is predictive of atherosclerotic disorders may depend on the population studied. We investigated whether metabolic syndrome is associated with carotid atherosclerosis in individuals who were shown not to have diabetes mellitus based on results of the 75-g oral glucose tolerance test (OGTT)., Methods and Results: Between 1994 and 2003, 3904 individuals underwent general health screening that included the OGTT. Among these 3904 individuals, 3679 had a fasting plasma glucose of <126 mg/dL (subgroup 1), and 3488 had a 2-h post-OGTT glucose value of <200mg/dL (subgroup 2). In both subgroups, metabolic syndrome was found to be a risk factor for carotid plaque and for carotid intima-media thickening in men, and tended to be a risk factor for carotid plaque in women after adjustment for age. Among 3473 individuals who had both a fasting plasma glucose value of <126 mg/dL and a 2-h post-OGTT glucose of <200mg/dL, 2440 did not have hypertension, which was defined as systolic and diastolic blood pressure of <140/90 mmHg and absence of use of anti-hypertensive medication. In these non-diabetic non-hypertensive individuals, the association between metabolic syndrome and carotid plaque or carotid intima-media thickening was not statistically significant even with adjustment only for age., Conclusions: In men who did not have impaired fasting glycemia and/or in those without impaired glucose tolerance, metabolic syndrome was a predictor of carotid atherosclerosis after age adjustment, although metabolic syndrome was not found to be a predictor of carotid atherosclerosis when hypertensive individuals were excluded from the study population.

We found that cigarette smoking increased white blood cell count, and individuals which increased white blood cell count more likely to have metabolic syndrome in Japanese men. We investigated whether similar relationship can be observed also in women. We analyzed the data from 16,383 Japanese women who underwent general health screening. Age-adjusted logistic regression analysis showed that current smoking was positively associated with a highest white blood cell count quartile with an odds ratio of 2.40 (95% CI: 2.16-2.68, P<0.0001). The white blood cell count showed a graded association with metabolic syndrome. On the other hand, the association between current smoking and metabolic syndrome was no longer significant after subdividing the individuals into groups according to the white blood cell quartile. These data collectively suggested that the association between current smoking and metabolic syndrome is heavily confounded by certain factors that increase the circulating white blood cell count in Japanese women, as in men.

Serum albumin is a maker of nutritional status and possesses antioxidative properties. Here, we have sought to investigate the mode of association between serum albumin levels, metabolic syndrome, and carotid atherosclerosis by analyzing the data of the cross-sectional data from 8143 individuals who underwent general health screening test. After adjusting for age, total cholesterol, and smoking status, the highest quartile of serum albumin (>or=4.7 g/dL) was associated with increased prevalence of metabolic syndrome with an odds ratio of 1.80 (95% CI 1.41-2.23, P<0.0001) in women, and 1.60 (95% CI 1.44-1.78, P<0.0001) in men, when compared to the lowest serum albumin quartile (<4.3g/dL). By contrast, when compared with the lowest quartile, the highest quartile of serum albumin was associated with reduced prevalence of carotid plaque with an odds ratio of 0.62 (95% CI 0.42-0.91, P<0.001) in women, and 0.76 (95% CI 0.62-0.93, P<0.01) in men, and for carotid intima-media thickening with an odds ratio of 0.57 (95% CI 0.35-0.94, P<0.05) in women, and 0.71 (95% CI 0.55-0.92, P<0.01) in men. Our data showed that higher serum albumin was inversely associated with the prevalence of early carotid atherosclerosis, although it was positively associated with the prevalence of metabolic syndrome. Whether these observations are in part explained by the antioxidative properties of albumin requires further investigation.

Aim: We have investigated whether metabolic syndrome is a risk factor for carotid atherosclerosis also in normotensive or prehypertensive individuals., Methods: We analyzed the data from 851 subjects who had a blood pressure of less than 140/90 mmHg and were not taking antihypertensive medication. Metabolic syndrome was defined according to three different criteria: Japan criteria (Japan-MetS); those of the National Cholesterol Education Program (NCEP)-Adult Treatment Panel III (ATP III) (NCEP-MetS); and modified NCEP-ATP III criteria in which body mass index was used as a surrogate for waist circumference (modified NCEP-MetS)., Results: Japan-MetS, NCEP-MetS, and modified NCEP-MetS were found, respectively, in 1%, 4%, and 4%, of women, and in 10%, 5%, and 9%, of men. After the adjustment for gender and age, the association between MetS and carotid atherosclerosis did not reach statistical significance., Conclusion: Although the number of enrolled subjects was relatively small, these data may further support the importance of controlling blood pressure within the optimal range for the purpose of preventing atherosclerosis in individuals with metabolic syndrome.

Objective: Cigarette smoking increases the circulating white blood cell (WBC) count and the prevalence of metabolic syndrome. We investigated the association between cigarette smoking, WBC count, and metabolic syndrome as defined by the Japanese criteria., Method: Cross-sectional data from 3,687 men undergoing general health screening between 2005 and 2006 were analyzed., Results: After adjustment for age and total cholesterol, former and current smoking were associated with the highest WBC quartile (>or=6.3 x 10(3) cells/muL) with an odds ratio of 1.35 (95% CI 1.09-1.66, P=0.0055) and 4.45 (95% CI 3.69-5.37, P<0.0001), respectively. It was found that increased WBC count was a risk factor for metabolic syndrome; on the other hand, the current smoking was not found to be a predictor for metabolic syndrome, when each WBC count quartile was separately analyzed., Conclusions: Our data suggest that the risk for MetS, defined by Japanese criteria, might be estimated by the WBC count in Japanese men irrespective of their smoking status, although it should also be noted that the cigarette smoking increases the number of circulating WBC count.

Much evidence indicates that metabolic syndrome is a risk factor for the development of cardiovascular disease, but whether metabolic syndrome is an independent risk factor for early atherosclerosis in the individuals with only minor hemodynamic abnormalities, if any, is not well investigated. Here we have investigated the association between metabolic syndrome and carotid atherosclerosis in individuals with blood pressure of <140/90 mm Hg. Between 1994 and 2003, 8143 subjects underwent general health screening including carotid ultrasonography. Of 8143 individuals, 5661 individuals without antihypertensive medications who had blood pressure of <140/90 mm Hg were considered to have optimal, normal, or high-normal blood pressure. After adjustment for age, systolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, triglycerides, fasting glucose, and smoking status, metabolic syndrome was not found to be an independent risk factor for carotid plaque (odds ratio: 1.65; 95% CI; 0.72 to 3.76 in women and odds ratio: 0.95; 95% CI: 0.70 to 1.28 in men) or for carotid intima-media thickening (odds ratio: 0.56; 95% CI: 0.18 to 1.72 in women and odds ratio: 0.93 95% CI: 0.62 to 1.38 in men) in these subjects. Thus, presence of metabolic syndrome may not increase the prevalence of carotid atherosclerosis independent of other cardiovascular risk factors in Japanese individuals with optimal, normal, or high-normal blood pressure.

Cigarette smoking is associated with increased insulin resistance and other metabolic abnormalities. Here, we investigate the prevalence of metabolic syndrome (MetS) in cigarette smokers and people who never smoked by analyzing cross-sectional data of 5033 subjects aged between 35 and 65 years who underwent general health screening. Both former and current smoking was associated with an increased incidence of metabolic syndrome defined by modified-National Cholesterol Education Program (NCEP) criteria with odds ratios of 1.77 (95% CI 1.42-2.22, P < 0.0001) and 2.38 (95% CI 1.95-2.91, P < 0.0001), respectively. In both former and current smokers, prevalence of metabolic syndrome increased when the duration of cigarette smoking was > or = 10 years. The positive association between metabolic syndrome and smoking was only partially reversed even 5 years after quitting. Multivariate logistic regression analysis showed that metabolic syndrome was an independent risk factor for carotid plaque with an odds ratio of 1.72 (95% CI 1.43-2.08, P < 0.0001). On the other hand, when limited to individuals without metabolic syndrome, former and current smoking was still found to be associated with carotid plaque with odds ratios of 1.49 (95% CI 1.15-1.92, P = 0.0023) and 1.57 (95% CI 1.22-2.03, P = 0.0005), respectively, in men. Collectively, these data suggest that the atherogenic consequences of smoking may, at least in part, be explained by its association with metabolic syndrome.

Objective: There are few data available on possible independent association between uric acid and carotid atherosclerosis. Here we first sought to investigate association between uric acid levels and metabolic syndrome in Japanese; second, we assessed whether there is an independent association of uric acid with prevalence of carotid atherosclerosis in individuals subdivided according to gender and metabolic syndrome status., Methods and Results: Cross-sectional data from 8144 individuals who underwent general health screening were analyzed. After adjusting for age, total cholesterol, and smoking status, the odds ratios (95% CI) of sex-specific quartiles of serum uric acid for metabolic syndrome were 1.0, 1.06 (0.60 to 1.87), 2.18 (1.30 to 3.64), and 4.17 (2.56 to 6.79) in women, and 1.0, 0.92 (0.74 to 1.14), 1.52 (1.25 to 1.65), and 1.97 (1.61 to 2.40) in men. After adjusting for age, serum levels, total cholesterol, and smoking status, prevalence of carotid plaque was higher in subjects in the second, third, and fourth quartiles of uric acid level with odds ratios (95% CI) of 1.24 (1.01 to 1.52), 1.37 (1.11 to 1.68), and 1.31 (1.05 to 1.63), respectively, in men without metabolic syndrome but not in men with metabolic syndrome or in women with or without metabolic syndrome., Conclusions: The prevalence of metabolic syndrome showed a graded increase according to serum uric acid values in both genders. In men who did not have metabolic syndrome, uric acid was found to be an independent risk factor for incidence of carotid plaque.

The cluster of metabolic and hemodynamic risk factors known as metabolic syndrome is known to be a risk factor for ischemic cardiovascular diseases and stroke. By analyzing the cross-sectional data from 8,144 individuals (age 19-88 years) who underwent general health screening, we have investigated the prevalence of metabolic syndrome, as diagnosed by modified-National Cholesterol Education Program (NCEP) criteria corresponding to the following five categories: triglycerides > or = 150 mg/dl; high density lipoprotein (HDL)-cholesterol < 40 mg/dl in men or < 50 mg/dl in women; fasting plasma glucose > or = 110 mg/dl; systolic/diastolic blood pressure > or = 130/85 mmHg; and body mass index > 25 kg/m2. We found that the prevalence of metabolic syndrome was 19% in men and 7% in women. After adjustment for age, metabolic syndrome was found to be significantly more prevalent in men than in women, with an odds ratio of 3.08 (95% confidence interval [CI] 2.62-3.61, p < 0.0001). Among the five metabolic/hemodynamic risk factor components, hypertension was observed most frequently in individuals with metabolic syndrome, at 85% in men and 87% in women. In addition, multivariate logistic regression analysis adjusted for age, sex, serum total cholesterol levels, and smoking status showed that hypertension possessed the greatest odds ratio (1.43, 95% CI 1.27-1.60) for carotid plaque among the metabolic/hemodynamic risk factors. These data emphasize the importance of controlling blood pressure for reducing the risk of both metabolic syndrome and carotid arteriosclerosis in apparently healthy individuals.