Nobuyuki Ohtsuka

An Association between Body Mass Index and Estimated Glomerular Filtration Rate

Chronic kidney disease (CKD) is a major public health problem. However, few studies have examined the significance of body mass index (BMI) as a risk factor for the development of CKD in the general Japanese population. Study participants without a clinical history of stroke, transient ischemic attack, myocardial infarction, angina or renal failure (754 men aged 56±15 [mean±SD] years and 962 women aged 59±13 years) were randomly recruited from a single community at the time of their annual health examination. We examined the relationship between increased weight (i.e., BMI) and renal function evaluated by the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. Increased BMI was consistently associated with reduced eGFR. Estimated GFR was lower in participants with upper normal body weight (BMI, 22.0 to 24.9 kg/m2) or who were overweight or obese (BMI≥25 kg/m2), compared with participants with lower normal body weight (BMI, 18.5 to 21.9 kg/m2). Stepwise multiple regression analysis using eGFR as an objective variable, adjusted for various risk factors as explanatory variables, showed that BMI (β = –0.075) was significantly and independently associated with eGFR, in addition to age, log triglycerides, low-density lipoprotein cholesterol and log fasting blood glucose. Compared with those with lower normal body weight, multivariate-adjusted odds ratios for moderately reduced renal function, defined as an eGFR < 60 mL/min/1.73 m2 , were 1.86 (1.01–3.42) for upper normal weight and 2.02 (1.01–4.03) for overweight or obese individuals. In conclusion, increased BMI is strongly associated with decreased eGFR in community-dwelling healthy persons.

High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons

BackgroundMetabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP.MethodsFrom a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR).ResultsOf these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders.ConclusionsThese results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.

Relationships between lipid profiles and metabolic syndrome, insulin resistance and serum high molecular adiponectin in Japanese community-dwelling adults.

BackgroundThere are few studies to demonstrate the associations between newly addressed lipid profiles and metabolic syndrome (MetS)-associated variables.MethodsStudy participants without medications for hypertension, diabetes, or dyslipidemia {614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years} were randomly recruited from a single community at the time of their annual health examination. The association between lipid profiles (total cholesterol (T-C), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, T-C/HDL-C, TG/HDL-C, LDL-C/HDL-C ratio and MetS, Insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR), and serum HMW adiponectin were analyzed.ResultsIn multiple linear regression analysis, TG/HDL-C and T-C/HDL-C ratios as well as TG showed significantly strong associations with all three MetS-associated variables in both men and women. In men, the ROC curve analyses showed that the best marker for these variables was TG/HDL-C ratio, with the AUC for presence of MetS (AUC, 0.82; 95% CI, 0.77-0.87), HOMA-IR (AUC, 0.75; 95% CI, 0.70-0.80), and serum HMW adiponectin (AUC, 0.67; 95% CI, 0.63-0.71), respectively. The T-C/HDL-C ratio, TG, HDL-C, LDL-C/HDL-C ratio, and non-HDL-C also discriminated these markers; however all their AUC estimates were lower than TG/HDL-C ratio. These results were similar in women.ConclusionIn Japanese community-dwelling adults, lipid ratios of TG/HDL-C, T-C/HDL-C, LDL-C/HDL-C as well as TG and HDL-C were consistently associated with MetS, insulin resistance and serum HMW adiponectin. Lipid ratios may be used as reliable markers.

A Slightly Low Hemoglobin Level Is Beneficially Associated with Arterial Stiffness in Japanese Community-Dwelling Women

Pulse wave velocity (PWV) is a simple and noninvasive method of measuring arterial stiffness for the assessment of cardiovascular disease in high-risk populations. This association may be further confounded by hemoglobin status, which is involved in the development of atherosclerosis. We randomly recruited 120 men and 223 women aged 69 ± 9 and 68 ± 7 years, respectively, during their annual health examination in a single community. Arterial stiffness was evaluated by brachial–ankle PWV (baPWV). The value of baPWV was different from men and women. In men, baPWV was not related to hemoglobin levels (r = 0.013, P = .886), but in women baPWV increased significantly and progressively with increased hemoglobin levels (r = 0.276, P < .001). Stepwise multiple regression analysis using the baPWV as objective variables, adjusted for confounding factors as explanatory variables, showed that only in women, hemoglobin levels (β = 0.165, P = .001) as well as age (β = 0.268, P < .001), body mass index (BMI; β = −0.165, P < .001), systolic blood pressure (SBP; β = 0.429, P < .001), prevalence of antihypertensive (β = 0.154, P = .002), heart rate (HR; β = 0.108, P = .017), and antilipidemic medication (β = 0.094, P = .036), and estimated glomerular filtration rate (eGFR; β = −0.147, P = .003) were significantly and independently associated with baPWV. Multivariate-adjusted baPWV was significantly higher in hemoglobin groups of ≥12.7 g/dL (Group-2, Group-4) than in the lowest hemoglobin group (10.0–12.6 g/dL; P = .032). A slightly low hemoglobin level was beneficially associated with arterial stiffness in community-dwelling women but not men.

Effect of weight loss on central systolic blood pressure in elderly community-dwelling persons.

Central blood pressure (BP) has been shown to strongly associate with cardiovascular disease and outcome. Recent studies have demonstrated a relationship between changes in body size by exercise training and peripheral BP; however, the effect on changes in central BP is unknown. The aim of this study was to assess whether changes in body size are independently related to changes in central BP in the elderly. The subjects were 11 men (mean age, 68±6 years) and 84 women (68±7 years) from a rural village. Before and at the end of the 12-week training program, metabolic variables, and first peak radial systolic BP (SBP1) and second peak radial SBP (SBP2) as estimates of central SBP, were obtained. Radial augmentation index (AI) was calculated as follows: ((SBP2−diastolic BP (DBP))/(SBP1−DBP)) × 100 (%) and we used AI corrected at heart rate 75 per min (AI@75). After the 12-week training program, weight loss correlated strongly with reduction in brachial mean arterial pressure (MAP), radial SBP1, SBP2 and AI@75. After adjusting for confounding factors, weight loss was significantly and independently associated with each reduction in brachial MAP (β=0.34, P=0.001), radial SBP1 (β=0.31, P=0.002), SBP2 (β=0.37, P<0.001) and AI@75 (β=0.36, P=0.001). These findings suggest that weight loss by a 12-week training program may be an effective strategy to improve central BP parameters among Japanese elderly persons.

Association between fasting plasma glucose and high-sensitivity C-reactive protein: gender differences in a Japanese community-dwelling population.

BackgroundHigh sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Hyperglycemia can potentially promote the production of CRP. The aim of this study was to determine whether increased fasting plasma glucose (FPG) levels are associated with elevated hsCRP concentrations by gender.MethodsWe recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether FPG levels are associated with hsCRP concentrations, and whether this association is independent of gender, body mass index (BMI) and other components of the metabolic syndrome.ResultsIn women only, hsCRP increased significantly and progressively with increasing FPG (r = 0.169, P < 0.001). The stepwise multiple linear regression analysis using hsCRP as an objective variable, adjusted for confounding factors as explanatory variables, showed that FPG as well as age, BMI, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), uric acid, and high molecular weight adiponectin were significantly associated with hsCRP in women, but not in men. There was significant gender interaction, and an increase in hsCRP levels that was greater in women with BMI ≥ 25 kg/m2 and higher FPG than in men.ConclusionsThese results suggested that hsCRP levels increase continuously across the FPG spectrum starting from the lowest FPG in both men and women. However, increase in hsCRP levels was greater in women than men.

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults.

BackgroundThe aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults.MethodsThis cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years. The study sample were 1,042 (74.8%) non-obese (BMI < 25.0 kg/m2) and 351 (25.2%) overweight (BMI ≥ 25 kg/m2) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. The areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers.ResultsIn non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio of 0.74 (95% confidence interval (CI), 0.66-0.80). The HDL-C, triglyceride (TG)/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38), 0.69 (95% CI, 0.62-0.75) and 0.69 (95% CI, 0.62-0.75), respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71) and 0.64 (0.57-0.70), respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio.ConclusionIn non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.

Serum High Molecular Weight Adiponectin Correlates with Arterial Stiffness in Community-Dwelling Persons

Introduction. Serum high molecular weight (HMW) adiponectin, an adipocytokine, which is a protein secreted specifically by adipose tissue, improves insulin sensitivity and plays an important role in the development of metabolic syndrome and cardiovascular disease (CVD). Pulse wave velocity (PWV) is a noninvasive method of measuring arterial stiffness for the assessment of CVD in high-risk populations. We investigated whether serum HMW adiponectin is independently associated with arterial stiffness when evaluated using PWV. Methods. We randomly recruited 99 men aged 69 ± 9 (mean ± standard deviation) years and 170 women aged 68 ± 7 years during their annual health examination in a single community. Peripheral arterial stiffness was evaluated by mean PWV determined at three points: from the heart to the carotid artery, to the brachial artery, and to the ankle. Results and conclusions. Age-adjusted PWV in all sites other than the heart to the carotid artery decreased progressively with increased serum HMW adiponectin. Age-adjusted mean PWV significantly decreased from the lowest to the highest serum HMW adiponectin group. Multiple linear regression analyses for mean PWV revealed that decreased serum HMW adiponectin levels were significantly associated with increased mean PWV as well as age, BMI, SBP, DBP, prevalence of antihypertensive medication, and eGFR. Inclusion of serum HMW adiponectin into the model further increased the coefficient of determination (R2). Multivariate-adjusted mean PWV was significantly lowest in the highest serum HMW adiponectin group.

Preperitoneal fat thickness by ultrasonography and obesity-related disorders

PurposeTo determine optimal cutoff values for preperitoneal fat thickness measured by ultrasonography as indicators for obesity-related disorders.MethodsWe studied 276 men aged 60 ± 13 years and 307 women aged 64 ± 11 years. Participants were consecutively enrolled from inpatients aged ≤75 years. Demographic data were collected and maximal preperitoneal fat thickness (PFTmax) and carotid intima-media thickness were evaluated on B-mode ultrasonography. Receiver operating characteristic (ROC) curve analysis was performed to determine optimal cutoff values for PFTmax.ResultsMultiple regression analysis using one or more obesity-related disorders as an objective variable showed that the tertile on the basis of PFTmax was a significant independent contributing factor in both men and women. Receiver operating characteristic curve analysis identified the cutoff points of 6.1 mm for PFTmax in men (sensitivity, 66.7%; specificity, 62.5%) and 8.7 mm for PFTmax in women (sensitivity, 56.6%; specificity, 63.6%) as discriminator values corresponding to the presence of one or more obesity-related disorders. Using the new criteria to diagnose visceral obesity, we found that adjusted carotid intima-media thickness was significantly higher in men and women with visceral obesity and two or more obesity-related disorders than in those without them.ConclusionsThese findings suggested that PFTmax measured on ultrasonography was useful in screening for indicators of cardiovascular risk factors.

Handgrip strength is associated with metabolic syndrome among middle-aged and elderly community-dwelling persons

Abstract The association of low muscle strength with cardio-metabolic risks remains controversial. The present study included 742 men aged 70 ± 9 years and 937 women aged 70 ± 8 years from a rural village. We examined the cross-sectional relationship between relative muscle strength defined by handgrip strength (HGS)/body weight (BW) ratio, and metabolic syndrome (MetS) based on the modified criteria of the National Cholesterol Education Program’s Adult Treatment Panel (NCEP-ATP) III report and its components. Of these, 203 men (27.4%) and 448 women (47.8%) had MetS. In men, increasing quartile of HGS/BW ratio was significantly and independently associated with high waist circumference {odds ratio, 0.31; 95% confidence interval (CI), 0.24–0.41} and elevated triglyceridemia (0.71, 0.59–0.86). In women, it was also significantly and independently associated with high waist circumference (0.41; 0.36–0.48), high blood pressure (0.78; 0.66–0.92), Low HDL-cholesterolemia (0.84; 0.73–0.98) and elevated triglyceridemia (0.65; 0.53–0.79). In both genders, the prevalence of MetS significantly decreased in relation to increasing HGS/BW ratio. After adjustment for age, smoking status, drinking status, LDL-C, estimated glomerular filtration ratio (eGFR), and medication, the respective odds ratio (95% CI) for the quartile of HGS/BW ratio for MetS was 1.00, 0.54 (0.34–0.85), 0.32 (0.19–0.53), and 0.16 (0.09–0.29) in men, and 1.00, 0.76 (0.50–1.16), 0.33 (0.22–0.51), and 0.16 (0.10–0.25) in women. These results suggest that HGS/BW ratio was significantly and negatively associated with an increased risk of cardio-metabolic disorders in Japanese-community dwelling persons.