Impact of changes in obesity parameters on glucose metabolism and insulin resistance over a one-year period.

AIM: Changes in indexes of obesity, such as waist circumference (WC) and body mass index (BMI), may influence some glucose metabolism-related parameters in both obese and non-obese subjects. We have investigated the impact of changes in WC and in BMI on data related to glucose metabolism over a one-year period. METHODS: Data from 3213 individuals (2014 men, 1199 women) who underwent a general health screening two years running and were not taking antidiabetic medication were analyzed. RESULTS: In men, percent changes in WC (%dWC) and BMI (%dBMI) were both significantly correlated with percent changes in fasting glucose (%dFG), in hemoglobin A(1C) (%dHbA(1C)), and in HOMA-IR (%dHOMA-IR). In women, these relationships were not significant except for the relationship between %dBMI and %dHOMA-IR. In a multivariate linear regression analysis using age, %dBMI, and %dWC as independent variables, %dBMI, but not %dWC, was found to be an independent predictor of %dHOMA-IR in both genders. Furthermore, in men, %dBMI was also an independent factor predicting %dFG and %dHbA(1C). CONCLUSION: During the one-year period, a reduction in BMI, and thus weight loss, was found to be associated with the improvement of insulin sensitivity, especially in men. A reduction in WC was also associated with an improvement in insulin sensitivity in men; however, this relationship did not remain significant after controlling for changes in BMI.

Association between gamma-glutamyltransferase levels and insulin resistance according to alcohol consumption and number of cigarettes smoked.

AIM: Alcohol intake may increase serum gamma-glutamyltransferase (GGT) but reduce insulin resistance. We analyzed the association between GGT and a marker of insulin resistance, homeostasis model assessment for insulin resistance (HOMA-IR), according to the drinking and smoking status. METHODS: After excluding former smokers and/or former drinkers, the data of 10,482 men who underwent general health screening were analyzed. RESULTS: Alcohol consumption showed a graded association with GGT. In men with current alcohol consumption of > or =40 g per day, > or =20 cigarettes per day further increased GGT levels. Alcohol consumption showed a U-shaped association with HOMA-IR. In contrast, smoking 20-39 and > or =40 cigarettes per day increased HOMA-IR as compared with never smokers. An interaction between alcohol consumption and smoking was present for GGT (p<0.001) and HOMA-IR (p=0.059). GGT was not a significant negative predictive value for HOMA-IR regardless of the drinking or smoking status. CONCLUSIONS: Although alcohol intake showed a graded association with GGT and a U-shaped association with HOMA-IR, serum GGT can be utilized as a predictor of insulin resistance in current drinkers.

Impact of changes in waist circumference and BMI over one-year period on serum lipid data in Japanese individuals.

AIM: Loss or gain in obesity indexes, such as body mass index (BMI) and waist circumference (WC), may affect serum lipid parameters. We therefore analyzed the impact of changes in WC and BMI over a one-year period on serum levels of LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides (TG). METHODS: We analyzed the data of 3,111 individuals who were not on lipid- lowering medication and who underwent general health screening two years running. RESULTS: The correlation between percent changes of WC (%dWC) and BMI (%dBMI) were both statistically significantly correlated with percent changes in LDL-C (%dLDL), HDL-C (%dHDL), and TG (%dTG) except that between %dWC and %dHDL in women. In multiple regression analysis, %dBMI, but not %dWC, was found to be an independent predictor of %dLDL, %dHDL, and %dTG. When %dBMI was excluded from the variables, %dWC was identified as an independent factor predicting %dLDL and %dTG; however, in individuals with %dBMI of > or =0, %dWC was not found to be a predictor of percent changes in any lipid parameters tested in this model. CONCLUSION: Percent changes in BMI were found to be an independent predictor of adverse changes in lipid parameters in both genders. Although percent changes in WC (%dWC) also tended to confer adverse changes in lipid parameters, this relationship did not remain statistically significant after controlling for %dBMI. It is suggested that changes in obesity parameters are an important goal to avoid adverse lipid changes, although there might be some gender differences.

Impacts of changes in obesity parameters for the prediction of blood pressure change in Japanese individuals.

AIMS AND METHODS: By analyzing data from 2,861 individuals who underwent general health screening 2 years running, we have investigated the impact of changes in waist circumference (WC) and body mass index (BMI) over a 1-year period on systolic blood pressure (BPs). We termed WC, BMI, and BPs at the first visit as WC1, BMI1, and BPs1, respectively, and those at the second visit as WC2, BMI2, and BPs2, respectively. The %dWC, %dBMI, and %dBPs was defined as (WC2 - WC1)/WC1 x 100, (BMI2 - BMI1)/BMI1 x 100, and (BPs2 - BPs1)/BPs1 x 100, respectively. RESULTS: In multivariate regression analysis using age, BPs1, WC1, and %dWC as independent variables, %dWC was a significant predictor for %BPs only in men. %dBMI was a significant predictor for %BPs in both genders when age, BPs1, BMI1, and %dBMI were used as independent variables. Compared with individuals with both %dWC <0 and %dBMI <0, age-adjusted %dBPs was significantly greater in those with both %dWC <0 and %dBMI >or=0; however, it did not significantly differ in those with both %dWC >or=0 and %dBMI <0. CONCLUSION: Our data suggest that the impact of BMI change might be greater than WC change in terms of BPs change during this short period.

Association between changes in obesity parameters and incidence of chronic kidney disease in Japanese individuals.

Obesity increases the risk for chronic kidney disease (CKD). By analyzing data on individuals who underwent general health screening in two consecutive years, we investigated whether changes in body mass index (BMI) or waist circumference (WC) were associated with the appearance or disappearance of the CKD components; micro-/macroalbuminuria (> or =30 mg urinary albumin per gram creatinine) and a low estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m(2)). Logistic regression analysis showed that in men with micro-/macroalbuminuria at the first visit, a BMI reduction of > or =0.42 or a WC reduction of > or =3.0 cm over the 1-year period resulted in a significantly reduced incident of micro-/macroalbuminuria at the second visit. On the other hand, a BMI gain of > or =0.33 over 1 year in men without micro-/macroalbuminuria and a low eGFR at the fist visit significantly increased the incident of micro-/macroalbuminuria and a low eGFR, respectively, at the second visit. These findings indicate that lowering the obesity indexes in men with micro-/macroalbuminuria reduced the incidence of this condition at the 1-year follow-up and that, on the contrary, an increase in BMI in men without micro-/macroalbuminuria and a low eGFR at the first examination increased the risk of these conditions during the 1-year follow-up period.

Relationship between albuminuria, low eGFR, and carotid atherosclerosis in Japanese women.

In this cross-sectional study, we have investigated whether chronic kidney disease components were associated with carotid plaque and carotid intima-media thickening in women. Between April 2005 and May 2006, 830 women underwent general health screening including carotid ultrasonography and urinary albumin excretion, and were enrolled in the study. Of these individuals examined, 83 (10%) had albuminuria, 203 (24%) had low estimated GFR (eGFR), and 24 (3%) had both albuminuria and low eGFR. Univariate analysis showed that albuminuria, but not low eGFR, was associated with carotid plaque, and that both albuminuria and low eGFR were positively associated with carotid intima-media thickening. Age-adjusted logistic regression analysis showed that albuminuria was positively associated with carotid plaque with an odds ratio of 2.48 (95% CI 1.49-4.11, p < 0.001). On the other hand, association between albuminuria and carotid intima-media thickening was not statistically significant after age adjustment. Positive association between albuminuria and carotid plaque was present when either hypertension or high fasting glucose was absent. In conclusion, in Japanese women who underwent general health screening, albuminuria, but not low eGFR, was positively associated with carotid plaque.

Association between cigarette smoking and chronic kidney disease in Japanese men.

Cigarette smoking may affect urinary albumin excretion and the glomerular filtration rate in both diabetic and nondiabetic subjects. Here we investigated the association between smoking and decreased or elevated glomerular filtration rate (GFR) and albuminuria by analyzing data from 7,078 Japanese men who had undergone a general health screening between 2005 and 2006. GFR was estimated with the Modified Diet in Renal Disease (MDRD) equation, and low estimated GFR (eGFR) and elevated eGFR were defined, respectively, as eGFR<60 and >90.7 mL/min/1.73 m2. Albuminuria was considered present when the urinary albumin excretion ratio (UAER), expressed as mg/g creatinine, was >or=30 mg/g. Multivariate logistic regression analysis showed that current smoking was associated inversely with low eGFR, and positively with albuminuria and elevated eGFR. The association between current smoking and low or elevated GFR was dependent on the number of cigarettes smoked per day. Former smoking was also significantly inversely associated with low eGFR, but the association between former smoking and albuminuria or elevated eGFR was not significant, even in individuals who had stopped smoking less than 1 year before. These data suggest that cigarette smoking may increase the prevalence of albuminuria and elevated eGFR or hyperfiltration, traits that might be reversed by smoking cessation. Although this concept should be verified by future longitudinal studies, our data suggest that we may need to take into account an individual's smoking status when assessing the presence or absence of chronic kidney disease because cigarette smoking may transiently increase eGFR.

Relationship between blood pressure and chronic kidney disease in the Japanese population: the lower the better even in individuals without hypertension?

In hypertensive subjects, it has been demonstrated that the lower the blood pressure, the lower the incidence of chronic kidney disease (CKD). However, whether this relationship holds true in individuals without hypertension--that is, in individuals with a blood pressure <140/90 mmHg--remains unknown. This study was performed to assess the relationship between blood pressure and CKD in a Japanese population without hypertension. Among 13,007 Japanese participants in a general health screening, 9,596 (5,691 men and 3,905 women) were found to have either normal blood pressure or prehypertension, and were enrolled in this study. We categorized these individuals' blood pressure into six classes: BP-C1, <90/<65 mmHg; BP-C2, 90-100/65-70 mmHg; BP-C3, 100-110/70-75 mmHg; BP-C4, 110-120/75-80 mmHg; BP-C5, 120-130/80-85 mmHg; and BP-C6, 130-140/85-90 mmHg. Albuminuria was defined as a urinary albumin excretion ratio of > or =30 mg/g. Low estimated glomerular filtration rate (eGFR) was defined as eGFR <60 mL/min/1.73 m2. In men, when BP-C3 was used as a reference, multivariate logistic regression analysis adjusted for age, body mass index, serum lipid profiles, fasting plasma glucose and smoking status showed that BP-C1, BP-C2, BP-C4, BP-C5 and BP-C6 were associated with albuminuria with an adjusted odds ratio of 1.85 (0.53-6.46), 1.22 (0.59-2.51), 1.62 (1.01-2.59), 2.57 (1.64-4.02), and 3.81 (2.44-5.96). In women, the adjusted odds ratios of the risk for albuminuria in BP-C2, BP-C3, BP-C4, BP-C5 and BP-C6, as compared with BP-C1 as a reference, were 1.83 (0.70-4.79), 2.13 (0.84-5.42), 2.80 (1.10-7.14), 2.59 (0.99-6.78), and 3.99 (1.50-10.64). Blood pressure was not significantly associated with low eGFR in either gender. The risk for albuminuria was significantly greater when blood pressure exceeded 110/75 mmHg in both genders.

Are serum carcinoembryonic antigen levels associated with carotid atherosclerosis in Japanese men?

OBJECTIVE: Carcinoembryonic antigen (CEA), a serological marker of malignant tumors, may show a modest increase under some nonmalignant conditions, such as ageing and cigarette smoking. We have investigated whether serum CEA levels are associated with early carotid atherosclerosis. METHODS AND RESULTS: Cross-sectional data from 4181 male individuals who underwent general health screening were analyzed. The interquartile of cutoff values of serum CEA levels were 1.0, 1.6, and 2.5 ng/mL. Cigarette smoking was associated with increased serum CEA levels in a dose- and duration-dependent manner, and this association was more prominent in current than former smokers. Logistic regression analysis adjusted for age, body mass index, serum lipid and glucose profiles, white blood cell count, C-reactive protein, and smoking habits showed that the first, second, third, and fourth CEA quartiles were associated with carotid plaque with an odds ratio of 1 (reference), 1.25 (95% CI 1.03 to 1.52, P=0.023), 1.49 (95% CI 1.23 to 1.82 P<0.001), and 1.34 (95% CI 1.08 to 1.65, P=0.007), respectively. Although serum CEA levels were associated with metabolic syndrome, association between serum CEA and carotid plaque was significant in individuals without metabolic syndrome. CONCLUSIONS: Serum CEA was associated with carotid atherosclerosis independently of atherogenic risk factors and markers of inflammation. Our data suggest that a slight elevation of CEA in current smokers, as well as in never smokers, may not be an innocuous observation from the viewpoint of atherosclerosis.

Association between cigarette smoking, white blood cell count, and metabolic syndrome as defined by the Japanese criteria.

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.

Is metabolic syndrome a risk factor for carotid atherosclerosis in normotensive and prehypertensive individuals?

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.

Relationship between smoking, white blood cell count and metabolic syndrome in Japanese women.

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.

Association between serum albumin, carotid atherosclerosis, and metabolic syndrome in Japanese individuals.

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.

Higher serum uric acid is associated with increased arterial stiffness in Japanese individuals.

Hyperuricemia is postulated to be a risk factor for atherosclerotic diseases, although whether it is independent of classical atherogenic risk factors is controversial. The automatic computer-assisted measurement of brachial-ankle pulse wave velocity (baPWV) is a valid and reproducible method by which to assess arterial stiffness, a potential surrogate marker of early atherosclerosis. By analyzing cross-sectional data from 982 individuals who underwent health screening, we have investigated whether serum uric acid is associated with high baPWV, which was determined as the highest quartile of baPWV values, in a sex-specific manner. Multivariate analysis showed that the odds ratios (95% CI) of the highest baPWV quartile across the sex-specific quartiles of serum uric acid were 1.0, 2.80 (0.93-8.40), 2.13 (0.74-6.19), and 2.76 (1.01-7.55) in women, and 1.0, 1.10 (0.55-2.20), 1.97 (1.04-3.75), and 2.24 (1.10-4.56) in men after adjusting for age, total and HDL-cholesterol, BMI, systolic blood pressure, triglycerides, fasting glucose and smoking status. The association between uric acid and high baPWV was observed in both subjects with metabolic syndrome and those without. These data suggest that in both genders, serum uric acid level is associated with increased baPWV, a marker of arterial stiffness, and is in part independent of other conventional risk factors for atherosclerosis and metabolic syndrome.

Association between chronic kidney disease and carotid intima-media thickening in individuals with hypertension and impaired glucose metabolism.

We investigated whether chronic kidney disease (CKD) was associated with carotid intima-media thickening in 1,351 male individuals undergoing general health screening. Glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease equations using 0.881 as a coefficient for Japanese, and low estimated GFR (eGFR) was defined as an eGFR value of <60 mL/min/1.73 m(2). Albuminuria was defined as a urine albumin-to-urine creatinine ratio of >or=30 mg/g, and CKD was defined when low eGFR and/or albuminuria was present. After adjusting for age, CKD was associated with carotid intima-media thickening with an odds ratio of 1.47 (95% confidence interval [CI] 1.05-2.06, p=0.0024). After adjusting for age, fasting plasma glucose, and smoking status, both albuminuria and low eGFR were significantly associated with intima-media thickening in individuals with hypertension with an odds ratio of 1.85 (95% CI 1.13-3.03, p=0.015) and 1.79 (95% CI 1.09-2.94, p=0.022), respectively. On the other hand, neither of them was associated with carotid intima-media thickening in individuals without hypertension. Similarly, after adjusting for age, systolic blood pressure, and smoking status, both albuminuria and low eGFR were significantly associated with intima-media thickening in individuals with high fasting glucose (defined as fasting plasma glucose levels of >or=110 mg/dL or current use of anti-diabetic medication), but not in those without. Our data indicate that CKD or its components (low eGFR and albuminuria) may be associated with early carotid atherosclerosis in low-risk individuals, such as those undergoing general health screening, who have hypertension and/or impaired glucose metabolism.

Association between obesity and chronic kidney disease in Japanese: differences in gender and hypertensive status?

Obesity is a known risk factor for hypertension and diabetes, both of which ultimately promote renal dysfunction. In the current study, we investigated the association between body mass index (BMI) and chronic kidney disease (CKD) in 8,168 Japanese individuals (2,924 women, 5,244 men) who underwent general health screening. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) was less than 60 mL/min/1.73 m(2) (designated as low eGFR) and/or if the urinary albumin/creatinine value was equal to or greater than 30 mg/g (designated as albuminuria). Logistic regression analysis adjusted for age, systolic blood pressure, fasting glucose, and smoking habits showed that, in men, both overweight (BMI 25-29 kg/m(2)) and obesity (BMI >or=30 kg/m(2)) were associated with increased prevalence of low eGFR and albuminuria, whereas, in women, obesity was associated with albuminuria, but neither overweight nor obesity was associated with low eGFR. After multivariate adjustment, logistic regression analysis showed that BMI had a graded association with both low eGFR and albuminuria in men. On the other hand, in women, the second and third BMI quartiles were associated with a lower prevalence of albuminuria in comparison with the first BMI quartile. Essentially the same results were obtained when the subjects were subdivided according to the presence and absence of hypertension. Our data showed that overweight and obesity were associated with increased risk for CKD in Japanese individuals undergoing a general health screening, irrespective of the presence or absence of hypertension, although there was a gender difference in these associations.

Metabolic syndrome may not associate with carotid plaque in subjects with optimal, normal, or high-normal blood pressure.

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.

Association between cigarette smoking, metabolic syndrome, and carotid arteriosclerosis in Japanese individuals.

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.