Akiko Toda

Plasma Free Amino Acid Profiles Predict Four-Year Risk of Developing Diabetes, Metabolic Syndrome, Dyslipidemia, and Hypertension in Japanese Population.

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.

Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects.

What is already known about this subject •  Asians with metabolic complications associated with obesity, a low body mass index and a low waist circumference have a greater proportion of visceral adipose tissue for a given amount of total body fat compared with Europeans. •  Apparent obese humans and obese animal models show an elevation of branched‐chain amino acid levels in plasma. •  A multivariate logistic regression model of plasma free amino acids has been used to screen for several types of cancers in clinical settings.

Changes in Waist Circumference and Body Mass Index in Relation to Changes in Serum Uric Acid in Japanese Individuals

Objective. Studies have shown that obesity is associated with an increase in serum uric acid; and few data are available on the relationship between changes in measures of obesity and changes in uric acid concentrations. We investigated the relationship among percentage changes in waist circumference (%dWC), body mass index (%dBMI), and serum uric acid (%dUA). Methods. The data of 3153 individuals [1968 men, 1185 women (536 premenopausal, 649 postmenopausal)] who underwent general health screening over a 2-year period and were not taking antihyperuricemic medication were analyzed. Results. Stepwise multiple regression analysis showed that %dBMI was associated positively with %dUA in postmenopausal women and men, and the association retained statistical significance after adjustment for changes in blood pressure and in renal function. Association between %dBMI and %dUA was not significant in premenopausal women. In men, %dWC was a predicting factor for %dUA, although it did not remain significant when %dBMI was used as a covariate in the statistical model. Multivariate logistic regression analysis showed that the odds ratio of the association between the lowest %dBMI quartile (%dBMI < –1.86) and the lowest %dUA quartile (%dUA < –7.41) was 2.04 (95% CI 1.35–3.07) in postmenopausal women and 1.46 (95% CI 1.14–1.86) in men. Conclusion. Weight loss may represent an effective nonmedical strategy for reducing serum UA levels, especially in postmenopausal women and men.

Hyperuricemia is a significant risk factor for the onset of chronic kidney disease.

Background: Recent studies have shown that hyperuricemia is an independent risk factor for cardiovascular disease. However, few studies have examined whether hyperuricemia is a risk factor for chronic kidney disease (CKD), so to investigate the significance of hyperuricemia as a risk factor for CKD, we analyzed data collected in annual health check-ups. Methods: The data of 11,048 subjects who underwent an annual health check-up were analyzed in cross-sectional and longitudinal studies. Results: After adjustment for covariate factors, a multivariate logistic regression analysis showed that age, systolic blood pressure, diastolic blood pressure, LDL-cholesterol, triglyceride, HbA1c, and uric acid (hazard ratio: 1.66) were independently and significantly associated with CKD. We also analyzed the data of 1,652 subjects who underwent annual health check-ups for 5 consecutive years. Over that 5-year period, 93 subjects developed CKD. We compared the baseline data of the subjects who developed CKD with the data of those who did not, and we found significant between-group differences in gender, age, HDL-cholesterol, the estimated glomerular filtration rate, and uric acid. After adjustment for several covariate factors, a multivariate Cox regression analysis showed that only age and hyperuricemia (hazard ratio: 1.36) were independent risk factors for the development of CKD. Conclusions: We found that hyperuricemia is an independent risk factor for the development of CKD.

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.

Relationship between Serum Uric Acid and Serum Oxidative Stress Markers in the Japanese General Population

Background: Increased production of reactive oxygen species is a condition that is associated with, and plays a role in the progression of, various disorders such as hypertension, atherosclerosis, and diabetes. Purpose: To assess in vivo oxidative stress levels and antioxidant potential and to analyze the relationship with serum uric acid (UA) levels. Methods and Results: Oxidative stress levels (derivatives of reactive oxygen metabolites, d-ROMs) and antioxidant potential (biological antioxidant potential, BAP) were measured in individuals who underwent a general health screening test, and data were analyzed from 8,025 individuals (2,953 women and 5,072 men) who were free from UA-lowering medication. Higher serum UA levels were associated with increased levels of d-ROMs in both genders, and this trend was more prominent in women. In addition, higher UA levels were also associated with higher BAP in both genders, although the dose dependence was not apparent in men. These associations remained statistically significant after adjusting for age, blood pressure, renal function, albuminuria, C-reactive protein, and insulin resistance index. Conclusions: In individuals who underwent general health screening, serum UA levels were positively associated with both d-ROMs and BAP levels. Whether lowering of UA by lifestyle modification or by medication alters d-ROM/BAP levels awaits further investigations.

Relationship between coffee consumption, oxidant status, and antioxidant potential in the Japanese general population.

Abstract Background: Several previous studies have demonstrated an association between habitual coffee intake and reduced risk of diabetes, cardiovascular morbidity and total mortality. Although the cause and effect relationship could not be determined through epidemiological data, antioxidant properties of coffee ingredients are presumed. Methods: In the current study, by analyzing the data from 9877 subjects (mean age 59.2±10.4 years) who underwent general health screening, we evaluated the extent of in vivo oxidative stress by measuring derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). Results: The mean levels of d-ROM and BAP were significantly lower in women than in men. By univariate analysis (ANOVA), coffee consumption showed a graded negative association with d-ROM value in men, but not in women. Coffee consumption was unrelated to BAP levels in men and women. Smoking was significantly associated with increased d-ROM and decreased BAP values in men. Multivariate-adjusted analysis showed that coffee intake of three or more cups per day was an independent negative correlate of d-ROM value in men. Sugar use was negatively associated with d-ROM and BAP values in women. Conclusions: Among an essentially healthy population, coffee intake was negatively associated with d-ROMs in men, but not in women. Whether the favorable effect of coffee, if present, is related to lower oxidative stress levels needs further investigation.

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 (≥30 mg urinary albumin per gram creatinine) and a low estimated glomerular filtration rate (eGFR; <60 ml/min/1.73 m2). Logistic regression analysis showed that in men with micro-/macroalbuminuria at the first visit, a BMI reduction of ≥0.42 or a WC reduction of ≥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 ≥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.

Current dietary salt intake of Japanese individuals assessed during health check-up

Excess salt intake is a risk factor for increased blood pressure (BP) and hypertension. To prevent hypertension, the reduction of salt intake is promoted in many countries. For people with hypertension or cardiovascular disease (CVD), a more severe restriction of salt intake is indispensable. Japanese individuals consume high quantities of salt, and it is thus important to determine the degree to which the salt intake of these individuals has been restricted. Here, we investigated the current level of salt consumption of Japanese individuals using data obtained during annual health check-ups. A total of 10 762 individuals were assessed who underwent annual health check-ups at our institution in 2011. The estimated daily salt intake (EDSI) was calculated using spot urine samples. The average EDSI was 7.83±2.02 g per day. BP increased in proportion to the EDSI, and multivariate logistic regression analysis showed that the EDSI was a significant and independent risk factor for hypertension. The average EDSI of the subjects with hypertension or a history of CVD was higher than that of the subjects without these diseases. The subjects who drank more heavily showed higher EDSIs. This study demonstrated that the average EDSI of the subjects needing to restrict their salt intake because of past or present illnesses was high. To achieve adherence to the recommended reduction of salt intake, more efforts are required.

Relationship between estimated glomerular filtration rate, albuminuria, and oxidant status in the Japanese population

BackgroundIn the general population, reported levels of oxidative stress and antioxidant potential seem to vary. The aim of this study was to investigate the levels of oxidant status markers in relation to estimated glomerular filtration rate (eGFR) and albuminuria in Japanese population.MethodsData were analyzed from 8335 individuals who underwent a general health screening test. For the estimation of albuminuria, urinary albumin-to-creatinine ratio (UAER) was calculated. Oxidant status was determined by assessing derivatives of reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP).ResultsAfter adjusting for age, high blood pressure, depressor agent use, CRP, smoking status, multivariate logistic regression analysis showed that the lowest eGFR quartile was associated negatively with the top d-ROM quartile in men (odds ratio 0.78 [95% CI 0.62-0.98, P = 0.034]) and the highest UAER was associated with the top d-ROM in men (odds ratio 1.68) [95% CI 1.35-2.10, P < 0.001]. In addition, both the first eGFR quartile and the fourth UAER quartile showed significant positive association with low BAP levels in men, but not in women.ConclusionsAmong men who underwent general health screening, lower eGFR and increased albuminuria was negatively and positively, respectively, associated with higher oxidative stress levels, whereas both conditions were positively associated with lower antioxidant potential levels.