Mika Takeuchi

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).

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.

Association of Pulse Pressure with Serum TNF-α and Neutrophil Count in the Elderly

Aims. Elevated pulse pressure (PP) has been reported to be a risk factor for type 2 diabetes in elderly patients with hypertension. Methods. Cross-sectional relationships of PP with known risk factors for type 2 diabetes and inflammatory markers were examined in 150 elderly community-dwelling women, 79 women (52.7%) of whom had hypertension. Results. Systolic blood pressure (standardized β, 0.775), log tumor necrosis factor-α (TNF-α, standardized β, 0.110), age (standardized β, 0.140), and neutrophil count (standardized β, 0.114) emerged as determinants of PP independent of high-sensitivity C-reactive protein, interleukin-6, monocyte count, plasminogen activator inhibitor-1, homeostasis model assessment of insulin resistance, HDL-cholesterol, and adiponectin (R 2 = 0.772). Conclusions. The present studies have demonstrated an independent association of higher PP with higher TNF-α, a marker of insulin resistance, and neutrophil count in community-living elderly women and suggest that insulin resistance and chronic low-grade inflammation may in part be responsible for the association between high PP and incident type 2 diabetes found in elderly patients with hypertension.

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.

Appendicular muscle mass and fasting triglycerides predict serum liver aminotransferases in young female collegiate athletes

Objective We test the hypothesis that aspartate aminotransferase (AST) may be associated inversely with serum triglycerides (TG) and positively with high density lipoprotein (HDL) cholesterol in young athletes because athletes have larger amounts of muscle mass. Research design and methods Pearson’s correlation coefficients were calculated between serum AST and alanine aminotransferase (ALT) and body composition identified by dual-energy X-ray absorptiometry, markers of insulin resistance, serum lipids, lipoproteins, apolipoproteins, adiponectin and leptin in 174 female collegiate athletes (18–22 years). Multivariate linear regression analyses were used to identify independent determinants of the aminotransferases. Results AST and ALT showed positive correlation with appendicular skeletal muscle mass (ASM) and height-adjusted ASM. In addition, ALT as well as AST showed inverse, not positive, association with fasting TG. Further, both AST and ALT showed positive associations with HDL cholesterol and apolipoprotein AI, a major apolipoprotein of HDL particles. Multivariate analysis revealed that height-adjusted ASM and TG (inverse) were independent determinants for AST and ALT. Further, fat mass index (inverse) and resting heart rate (inverse) predicted AST and apolipoprotein AI predicted ALT. Conclusions In young female collegiate athletes, both serum AST and ALT showed inverse association with fasting TG and positive association with apoAI, both of which may be mediated through positive association between the aminotransferases and ASM. The association between ALT and TG is opposite in direction in young athletes (inverse) and in the general population (positive).

Elevated serum adiponectin and tumor necrosis factor-α and decreased transthyretin in Japanese elderly women with low grip strength and preserved muscle mass and insulin sensitivity

Objective To determine if adiponectin levels are associated with low grip strength among the elderly independently of insulin resistance and inflammation. Research design and methods Cross-sectional associations were analyzed by logistic regression between low grip strength and body composition, elevated serum adiponectin (≥20 mg/L), and biomarkers of nutritious stasis, insulin resistance and inflammation in 179 community-living Japanese women. Sarcopenia was evaluated using the Asian criteria. Results No women had sarcopenia. In bivariate analyses, low grip strength (n=68) was positively associated with age, log tumor necrosis factor-α (TNF-α) and hyperadiponectinemia (n=37) and inversely with body weight, height, skeletal muscle mass, serum albumin, transthyretin (TTR), fat mass, serum zinc and hemoglobin (all p<0.01). In a fully adjusted model, TTR (0.90: 0.83–0.98, p=0.01) in addition to age (p=0.007), height (p=0.004) and skeletal muscle mass (p=0.008) emerged as independent determinants of low grip strength. When TTR was removed from the full model, TNF-α was associated with low grip strength (7.7; 1.3–45.8, p=0.02). Mean waist circumference and high-density lipoprotein cholesterol did not differ between women with and without low grip strength and were within the respective normal range. Women with hyperadiponectinemia had higher percentage of women with low grip strength and lower grip strength (both p<0.01). Conclusions Hyperadiponectinemia and elevated TNF-α in addition to decreased TTR, a biomarker of age-related catabolic states, were found in community-living Japanese elderly women with low grip strength and preserved muscle mass and insulin sensitivity.

Association of serum orosomucoid with 30-min plasma glucose and glucose excursion during oral glucose tolerance tests in non-obese young Japanese women

Objective Inflammatory markers are elevated in insulin resistance (IR) and diabetes. We tested whether serum orosomucoid (ORM) is associated with postload glucose, β-cell dysfunction and IR inferred from plasma insulin kinetics during a 75 g oral glucose tolerance test (OGTT). Research design and methods 75 g OGTTs were performed with multiple postload glucose and insulin measurements over a 30–120 min period in 168 non-obese Japanese women (aged 18–24 years). OGTT responses, serum adiponectin and high-sensitivity C reactive protein (hsCRP) were cross-sectionally analyzed by analysis of variance and then Bonferroni’s multiple comparison procedure. Stepwise multivariate linear regression analyses were used to identify most important determinants of ORM. Results Of 168 women, 161 had normal glucose tolerance. Postload glucose levels and the area under the glucose curve (AUCg) increased in a stepwise fashion from the first through the third ORM tertile. In contrast, there was no or modest, if any, association with fat mass index, trunk/leg fat ratio, adiponectin, hsCRP, postload insulinemia, the Matsuda index and homeostasis model assessment IR. In multivariable models, which incorporated the insulinogenic index, the Matsuda index and HOMA-IR, 30 min glucose (standardized β: 0.517) and AUCg (standardized β: 0.495) explained 92.8% of ORM variations. Conclusions Elevated circulating orosomucoid was associated with elevated 30 min glucose and glucose excursion in non-obese young Japanese women independently of adiposity, IR, insulin secretion, adiponectin and other investigated markers of inflammation. Although further research is needed, these results may suggest a clue to identify novel pathways that may have utility in monitoring dysglycemia within normal glucose tolerance.

Associations of postprandial lipemia with trunk/leg fat ratio in young normal weight women independently of fat mass and insulin resistance

BACKGROUND AND OBJECTIVES To determine whether postprandial lipemia is associated with fat distribution even in young, normal weight women independently of fat mass, adipokines, insulin resistance and systemic inflammation. METHODS AND STUDY DESIGN Female college students (ages 21-24, n=35) underwent dual-energy X-ray absorptiometry and a standardized breakfast providing 17 g triglycerides (TG). Serum lipids, lipoproteins, apolipoproteins, adipokines and markers of insulin resistance and inflammation were measured in fasting blood samples. RESULTS In crude analyses, postprandial lipemia, as assessed by 0-2 h area under the curve of serum TG (TG-AUC), was positively associated with fasting TG, trunk/leg fat ratio, apolipoprotein B, leptin/adiponectin ratio and log high-sensitivity CRP. Multiple linear regression analysis with these 5 variables as independent variables revealed that fasting TG (p<0.001) and trunk/ leg fat ratio (p=0.001), were independent positive predictors of TG-AUC (R2=0.923). Women with high compared to low TG-AUC were characterized by higher trunk/leg fat ratio, elevated apolipoprotein B and leptin/adiponectin ratio. CONCLUSION Trunk/leg fat ratio, a marker of central adiposity, is a significant predictor of postprandial lipemia even in young women who are normal weight and insulin- sensitive, suggesting a modifiable pathway to postprandial hypertriglyceridemia, a cardiometabolic risk factor. These findings should be confirmed in studies employing more participants.