Ayaka Tsuboi

Serum copper, zinc and risk factors for cardiovascular disease in community-living Japanese elderly women

BACKGROUND Associations of copper (Cu) and zinc (Zn) serum levels with risk factors for cardiovascular disease (CVD) have not been extensively studied in elderly Asian people. METHODS Relationships to CVD risk factors were examined in 202 freely-living elderly Japanese women. RESULTS By univariate analysis, log high-sensitivity C-reactive protein (hsCRP) and non-HDL cholesterol were associated with serum Cu concentrations. An independent predictor of Cu was log hsCRP. Serum Zn concentrations decreased with age. After adjustment for age, serum albumin, HDL cholesterol and red blood cell (RBC) were positively and serum insulin and log hsCRP were inversely associated with serum Zn. In stepwise multiple regression analysis (model 1), serum albumin and HDL cholesterol were associated with serum Zn. In analysis excluding albumin from model 1 (model 2), independent determinants were log hsCRP (inverse) and the total number of RBC. In analysis including serum creatinine in model 2, creatinine has emerged as a determinant in addition to log hsCRP and RBC number. In analysis including estimated glomerular filtration rate (eGFR) instead of creatinine and excluding age in model 2, eGFR has emerged as a determinant of serum Zn in addition to log hsCRP and RBC number. CONCLUSIONS Systemic low-grade inflammation may contribute to elevated serum Cu and decreased serum Zn concentrations in the elderly, and may represent an important confounder of the relationship between the serum trace elements and mortality in this population.

Association of Metabolic Syndrome with Chronic Kidney Disease in Elderly Japanese Women: Comparison by Estimation of Glomerular Filtration Rate from Creatinine, Cystatin C, and Both.

BACKGROUND Associations between metabolic syndrome (MetS) and chronic kidney disease (CKD) has not been extensively studied in elderly Asians, who in general have lower body mass index (BMI) than European populations. METHODS A cross-sectional analysis was conducted including 159 community-living elderly Japanese women. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, but using a BMI ≥25 kg/m(2) instead of waist circumference and renal function was assessed according to the Kidney Disease Outcomes Quality Initiative CKD classification. Creatinine-based and cystatin C-based estimated glomerular filtration rate (eGFR) and the average of the two eGFRS were used. RESULTS Prevalence of CKD was much higher when creatinine-based eGFR was used than the prevalence obtained when cystatin-C based equations were used (46.5% vs. 12.6%, P < 0.001). Eighteen (11.3%) women met MetS criteria. Both the presence of MetS and the number of MetS components were associated with higher prevalence of CKD using the average eGFR (all P < 0.05) but not using creatinine-based (P = 0.86) and cystatin C-based (P = 0.12) eGFR alone. Lower average eGFR and higher prevalence of CKD using average eGFR were evident in even women with only one MetS component, 89% of whom had elevated blood pressure. CONCLUSIONS Prevalence of CKD varied substantially depending on the used equation. In nonobese, elderly Japanese women, both the presence of MetS and the number of MetS components were associated with higher prevalence of CKD and elevated blood pressure may play an important role in these associations. These findings should be confirmed in studies employing more participants with MetS diagnosed using standard criteria (waist circumference instead of BMI).

Direct association of visit-to-visit HbA1c variation with annual decline in estimated glomerular filtration rate in patients with type 2 diabetes.

Background/AimsThis study examined associations of visit-to-visit variability of glycemic control with annual decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes attending an outpatient clinic.MethodsIntrapersonal mean and coefficient of variation (CV) of 8-12 measurements of HbA1c and those of 4-6 measurements of fasting and post-breakfast plasma glucose (FPG and PPG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 patients with type 2 diabetes. Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR.ResultsCV-HbA1c (standardized β、-0.257、p = 0.004) were significantly and log urine albumin/creatinine ratio (standardized β、-0.155、p = 0.085) and smoking (standardized β、-0.186、p = 0.062) tended to be associated with annual eGFR decline independently of mean HbA1c, age, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG, PPG and systolic blood pressure, baseline eGFR, and uses of anti-hypertensive and lipid-lowering medications. Association between HbA1c variability and renal function decline was stronger in patients with albumin/creatinine ratio ≧ 30 mg/g than in those with normoalbuminuria (r = -0.400, p = 0.003 and r = -0.169, p = 0.07, respectively).ConclusionsConsistency of glycemic control is important to preserve kidney function in type 2 diabetic patients, in particular, in those with nephropathy.

Low haemoglobin levels contribute to low grip strength independent of low-grade inflammation in Japanese elderly women

Muscle strength declines with age. However, factors that contribute to such declines are not well documented and have not been extensively studied in elderly populations of Asian origin. Correlations of grip strength with a broad range of factors associated with declines in muscle strength were examined in 202 community-living elderly Japanese women. After adjustment for age, grip strength was positively correlated with body weight, height, serum albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C) and serum iron and inversely with serum copper, and log high-sensitivity C-reactive protein (hsCRP). Multiple linear regression analysis with grip strength as a dependent variable showed that 47.0% of variability of grip strength could be accounted for by height, age and haemoglobin in order of increasing R2. In conclusion, low haemoglobin may contribute to low muscle strength independently of age, anthropometric, nutritional, and inflammatory markers in the elderly, and may represent an important confounder of the association between grip strength and functional decline in community- living Japanese elderly women.

Association of Metabolic Syndrome with Serum Adipokines in Community-Living Elderly Japanese Women: Independent Association with Plasminogen Activator-Inhibitor-1

BACKGROUND Associations between metabolic syndrome (MetS) with serum adipokines and basal lipoprotein lipase mass (serum LPL) have not been extensively studied in elderly Asians, who in general have lower body mass index than European populations. METHODS A cross-sectional analysis was conducted including 159 community-living elderly Japanese women whose age averaged 77 years. MetS was defined by the modified National Cholesterol Education Program Adult Treatment Panel III criteria, but using a body mass index ≥25 kg/m(2) instead of waist circumference. Serum LPL, leptin, adiponectin, plasminogen activator inhibitor 1 (PAI-1), interleukin-6, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were measured. RESULTS Both the presence of MetS and the number of MetS components were associated with higher homeostasis assessment of insulin resistance, serum levels of leptin, PAI-1, and tumor necrosis factor-alpha and with lower serum levels of LPL and adiponectin (all P < 0.05), but not with high-sensitivity C-reactive protein and interleukin-6. Among six biomarkers of MetS, PAI-1 remained associated with MetS independent of fat mass index and insulin resistance. CONCLUSIONS Although proinflammatory, prothrombotic, and anti-inflammatory states were associated with MetS, higher PAI-1 was associated with MetS independent of fat mass index and insulin resistance in elderly Japanese women, in whom obesity is rare.

Association of Cystatin C with Leptin and TNF-α in Elderly Japanese Women

BACKGROUND AND OBJECTIVES Determinants of cystatin C, a novel marker of mortality in the elderly, have not been extensively studied in Asian elderly population. METHODS AND STUDY DESIGN Associations of cystatin C with anthropometric, cardiometabolic, hematological, nutritional variables and inflammatory markers were examined in 159 community-living elderly Japanese women whose BMI averaged 22.6±2.9 (SD) kg/m2. RESULTS Serum creatinine and cystatin C averaged 0.73±0.16 mg/dL and 0.85±0.20 mg/L, respectively. Creatinine-based estimated glomerular filtration rate (standardized β, -0.538, p<0.001), age (standardized β, 0.274, p<0.001), serum leptin (standardized β, 0.218, p<0.001) and tumour necrosis factor-α (TNF-α, standardized β, 0.165, p=0.002) emerged as significant predictors of serum cystatin C independent of percentage body fat, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, systolic blood pressure and HDL cholesterol (cumulative R2=0.674). CONCLUSIONS Elevated serum levels of leptin and TNF-α contributed to elevated cystatin C independent of kidney function, fat mass, insulin resistance and inflammation in community-living elderly women and may represent confounders of associations between cystatin C and mortality in this population.

Associations of Decreased Serum Transthyretin with Elevated High-sensitivity CRP, Serum Copper and Decreased Hemoglobin in Ambulatory Elderly Women

BACKGROUND Transthyretin (TTR), a sensitive indicator of malnutrition and inflammation, has been shown to be associated with mortality in elderly population. METHODS We examined relationships between serum TTR and a range of risk factors for mortality in 185 free-living elderly women. Blood was drawn between breakfast and lunch. RESULTS TTR was correlated negatively with age (r=-0.30, p<0.001). After controlling for age, TTR was negatively associated with log high-sensitivity CRP (hsCRP) and serum copper. It was positively associated with albumin, serum iron and hemoglobin. In addition, TTR was positively correlated with systolic and diastolic blood pressure and postprandial triglyceride (TG). In multiple regression analysis for TTR as a dependent variable, hemoglobin (standardized β, 0.244), serum copper (standardized β, -0.134), postprandial TG (standardized β, 0.223) and log hsCRP (standardized β, -0.190) emerged as determinants of TTR independently of age, albumin, serum iron, systolic and diastolic blood pressure, and explained 22.8% of TTR variability. CONCLUSIONS Subclinical low-grade inflammation, elevated serum copper and decreased hemoglobin were associated with decreased serum TTR in community-living elderly Japanese women and may represent important confounders of the relationship between low TTR and mortality in the elderly. The positive association of TTR with postprandial TG warrants further investigation.

Association of Postbreakfast Triglyceride and Visit-to-Visit Annual Variation of Fasting Plasma Glucose with Progression of Diabetic Nephropathy in Patients with Type 2 Diabetes

Urinary albumin/creatinine ratio (ACR) was measured at baseline and after a median follow-up of 6.0 years in 161 patients with type 2 diabetes. Intrapersonal means and SD of HbA1c, systolic BP, fasting, and postmeal plasma glucose (FPG and PMPG, resp.) and serum triglycerides (FTG and PMTG, resp.) were calculated in each patient during the first 12 months after enrollment. Associations of these variables with nephropathy progression (15 patients with progression of albuminuric stages and 5 with ACR doubling within the microalbuminuric range) were determined by multivariate logistic regression analysis providing odds ratio with 95% confidential interval. Patients with nephropathy progression, compared with those without nephropathy progression, had higher HbA1c (p < 0.01). They also had higher means and SD of FPG (both p < 0.05), FTG (both p < 0.05), and PMTG (p = 0.001). Multivariate logistic regression analysis demonstrated that SD-FPG (1.036, 1.001–1.073, p = 0.04) and PMTG (1.013, 1.008–1.040, p = 0.001) were significant predictors of progression of nephropathy even after adjustment for mean FPG and SD-FTG, age, sex, BMI, waist circumference, diabetes duration and therapy, means and SDs of HbA1c, PPG, FTG and systolic BP, baseline ACR, smoking status, and uses of antihypertensive and lipid-lowering medications. Consistency of glycemic control and management of postmeal TG may be important to prevent nephropathy progression in type 2 diabetic patients.

Inverse Association of Serum Leptin with Flow-Mediated Dilatation Independent of Body Fat Distribution, Insulin Resistance, Oxidative Stress and Inflammation in Young Women

Chronic hyperleptinemia found in obesity has been shown to be associated with endothelial dysfunction, an early and fundamental event in the development of atherosclerosis. We examined whether elevated leptin levels are associated with decreased endothelial function in young women. Flow-mediated dilatation (FMD) in the brachial artery, fat mass by dual-energy absorptiometry, Matsuda index, an insulin sensitivity index derived from an oral glucose tolerance test, serum leptin, adiponectin, hepatic enzymes, lipid profile, high-sensitivity C-reactive protein (hsCRP) and urinary 8-epi-prostaglandin F- 2α (8-epi-PGF 2α ), a marker of oxidative stress, were measured in 44 young women. After adjustment for age, FMD was associated inversely with percentage of body fat, trunk fat and leg fat. In addition, FMD showed inverse associations with serum leptin, log hsCRP and log alanine aminotransferase (all p<0.05 or less). In multiple regression analysis only leptin emerged as an independent determinant of FMD (standardized beta、-0.325) and explained 11% of FMD variability. In conclusion, leptin serum levels had an impact on arterial distensibility in young women, a finding that raises the possibility that leptin levels in the general population during early adulthood may already be relevant to the development of vascular dysfunction.

Higher Fasting and Postprandial Free Fatty Acid Levels Are Associated With Higher Muscle Insulin Resistance and Lower Insulin Secretion in Young Non-Obese Women

Background To assess the relationship of the shape of glucose concentration curve during a standardized meal test to serum free fatty acid (FFA) concentrations, insulin resistance and insulin secretion in young non-obese women. Methods Thirty-five young women had a standardized meal for breakfast with measurement of glucose, insulin and FFA concentrations at 0 (fasting), 30, 60 and 120 min; the areas under the concentration curves were calculated (AUCg, AUCi and AUCffa, respectively). Meal-induced insulin response (MIR) was calculated as the ratio between the incremental insulin and glucose concentrations during the first 30 min of meal tests. In two women (group A), post-breakfast glucose (PBG) returned to levels below fasting plasma glucose (FPG) at 30 min; in 15 and 11 women, PBG returned to levels below FPG at 60 and 120 min (groups B and C, respectively). In the remaining seven women (group D), PBG never fell below FPG. Results Despite no difference in fasting insulin and AUCi, fasting FFA, AUCg and AUCffa were the lowest in group A, increased linearly from group B to C and plateaued in group D, whereas MIR might be the highest in group A, decreased from group B to C and plateaued in group D. Conclusion Young women whose PBG returned to FPG more slowly had higher muscle insulin resistance and lower MIR associated with higher fasting and postprandial FFA levels compared with young women whose PBG returned to baseline more quickly.