Healthy Japanese Research Articles

Associations Between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Metabolic Syndrome, Insulin Resistance, and Lifestyle Habits in Healthy Japanese.

Background: The triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio is related to insulin resistance (IR). However, little information is available on whether TG/HDL-C is associated with IR and components of metabolic syndrome (MetS) and how lifestyle habits affect TG/HDL-C in the healthy Japanese population. Methods: In total, 1068 Japanese subjects who had undergone an annual health examination and who were not receiving medication were recruited. Determinants for TG/HDL-C ratio were investigated using multiple regression analyses. The subjects were divided into three groups by lifestyle habits (i.e., smoking, exercise, and physical activity), homeostasis model assessment of IR (HOMA-IR), and fasting plasma glucose, four groups by alcohol intake, and five groups by numbers of MetS components to compare TG/HDL-C values. All analyses were done separately by sex. Results: Multiple regression analyses revealed that waist circumference and smoking were positively associated with TG/HDL-C in both men and women, whereas physical activity was negatively associated with TG/HDL-C ratio in women. TG/HDL-C increased with increasing number of MetS in both men and women. TG/HDL-C increased as HOMA-IR increased in both men and women, when subjects were stratified according to HOMA-IR. TG/HDL-C values were lower in both men and women who exercised regularly, had high physical activity, or were nonsmokers. Independent of exercise and physical activity, TG/HDL-C was higher in smokers than in nonsmokers for both men and women. The relationship between TG/HDL-C and alcohol intake was not statistically significant in both men and women. Conclusions: The TG/HDL-C ratio is associated with IR, components of MetS, exercise, physical activity, and smoking, but not alcohol intake, in healthy Japanese subjects.

Comparative pharmacokinetics of maxacalcitol in healthy Taiwanese and Japanese subjects

Pharmacokinetic studies of maxacalcitol in healthy Taiwanese subjects have been conducted. This study to compare the pharmacokinetic properties of maxacalcitol in healthy Taiwanese and Japanese subjects. Healthy male Taiwanese subjects (n = 24) and healthy male Japanese subjects (n = 24) were enrolled in separate single-center and received a single intravenous dose of 1.25, 2.5 and 5 μg maxacalcitol. Male subjects were exclusively employed in the study due to the first administration of maxacalcitol to Taiwanese.Serum samples were collected for up to 72 h for pharmacokinetic analysis, and safety was assessed. Exposures to maxacalcitol as mean C5 and AUCinf appeared to increase with increase of doses in Taiwanese subjects (C5: 74.0, 159, and 321 pg/mL; AUCinf: 473, 763, and 1460 h･pg/mL) and Japanese subjects (C5: 92.9, 174, and 346 pg/mL; AUCinf: 312, 588, and 1040 h･pg/mL). After single bolus IV administration, linearity in maxacalcitol exposure was shown over the dose range of 1.25–5 μg in both Taiwanese and Japanese male healthy subjects. C5 of maxacalcitol was slightly lower (85%) in Taiwanese compared with that in Japanese and AUCinf of maxacalcitol in Taiwanese subjects was contrarily 15.0 (41.6%) higher than that in Japanese subjects, resulted in not much difference in pharmacokinetics of maxacalcitol between Taiwanese and Japanese. Moreover, maxacalcitol was well tolerated in both healthy Taiwanese and Japanese subjects.

Relationship among independence of daily living, human relationships, and preparation for bereavement among healthy elderly Japanese people.

Given Japan's rapidly ageing society, an increasing number of elderly people live in their communities with mutual support after the death of their spouse. The purpose of this study is to clarify the relationship among independence of daily living, human relationships, and preparation for bereavement. An anonymous, self-administered questionnaire was given to 864 community-dwelling elderly people aged 65 and older who attended an Elderly Citizens' Welfare Study Group. A total of 404 responses (effective response ratio: 46.8%) were analyzed. Their mean ± SD age was 75.6 ± 5.1 years. The purpose of the questionnaire was to obtain demographic information as well as information about three scales: independence of daily living, human relationships, and preparation for bereavement. The factor structure of the scales was studied by using exploratory and confirmatory factor analysis. Structural equation modelling was used to investigate the relationship among independence of daily living, human relationships, and preparation for bereavement. This study's protocol was approved by the Ethics Committee of Okayama Prefectural University. Factor analysis indicated a three-factor second-order factor model for independence of daily living and human relationships and a one-factor model for preparation for bereavement. Structural equation modelling showed that independence of daily living was significantly correlated with human relationships (r = 0.261, P < 0.001), and human relationships was significantly correlated with preparation for bereavement (r = 0.295, P < 0.001). There was no significant direct correlation between the independence of daily living and preparation for bereavement. Encouraging elderly people to form good human relationships may help their preparation for bereavement. Further studies are required to determine whether this actually attenuates difficulties after bereavement.

Complete Genome Sequence of Akkermansia muciniphila JCM 30893, Isolated from Feces of a Healthy Japanese Male.

Akkermansia muciniphila is an anaerobic and mucin-degrading bacterium in the human gut. Here, we report the complete genome sequence of Akkermansia muciniphila JCM 30893 harboring the plasmid pJ30893.

Draft Genome Sequences of Bifidobacterium animalis Consecutively Isolated from Healthy Japanese Individuals.

Bifidobacterium species are well recognized as probiotics and colonized in various parts of the human body. Here, we report the draft genome sequences of Bifidobacterium animalis isolated from two healthy Japanese volunteers, one of which was sampled twice before and after a 10-year interval. A core genome phylogeny analysis indicated that the strains isolated from the same volunteer were closely related. This paper is the first report of multiple draft genome sequences of B. animalis independently isolated from the same individual and provides insight into the probiotic potential of a member of this species.

Copy Number Variation of the Salivary Amylase Gene and Glucose Metabolism in Healthy Young Japanese Women.

BackgroundMany studies have shown that low copy number variation (CNV) of the salivary amylase gene (AMY1) and low serum amylase concentration are associated with impaired glucose metabolism and obesity. We aimed to clarify the conflicting results of previous studies by examining AMY1 expression and metabolic indices in a homogenous group of healthy participants.MethodsSixty healthy non-obese young Japanese women aged 20 - 39 years were examined for AMY1 CNV, salivary amylase, body mass index (BMI) and serum parameters including glycated hemoglobin (HbA1c), ketones, and total, salivary and pancreatic amylase. Respiratory quotient at rest and changes in blood glucose after starch loading were also examined.ResultsAMY1 CNV (range, 4 - 14) and the level of serum salivary amylase were correlated inversely with HbA1c (r = -0.36, P = 0.003 and r = -0.30, P = 0.02, respectively), whereas the percentage of serum salivary amylase in total serum amylase was positively correlated with blood glucose at 30 and 45 min after starch loading (r = 0.38, P = 0.004 and r = 0.27, P = 0.04, respectively). The level of serum total amylase, but not AMY1 CNV, was correlated inversely with BMI (r = -0.29, P = 0.02). Logistic regression analysis showed that low AMY1 CNV (4 - 7) was significantly associated with an HbA1c of ≥ 5.4% (34 mmol/mol) even after adjustment for age, BMI and energy consumption, compared with high AMY1 CNV (8 - 14).ConclusionsAlthough a higher percentage of serum salivary amylase was associated with higher levels of blood glucose at the early stage after starch loading, low AMY1 CNV was associated with chronic unfavorable glucose metabolism in healthy non-obese young women in Japan.

Micronutrient Intake Adequacy in Men and Women with a Healthy Japanese Dietary Pattern.

This study examined the relationship between a healthy Japanese dietary pattern and micronutrient intake adequacy based on the Dietary Reference Intakes for Japanese 2015 (DRIs-J 2015) in men and women. A cross-sectional study was conducted in 1418 men and 795 women aged 40–87 years, who participated in the Waseda Alumni’s Sports, Exercise, Daily Activity, Sedentariness, and Health Study. Dietary patterns were derived from principal component analysis of the consumption of 52 food and beverage items, which were assessed by a validated brief-type self-administered diet history questionnaire. Micronutrient intakes were quantified using the dietary reference intakes score (DRIs-score) for 21 micronutrients (based on DRIs-J 2015). The healthy dietary pattern score was significantly and positively correlated with the intakes of all 21 micronutrients used for constructing the DRIs-score in men and in women (each, p < 0.001). In both sexes, the healthy dietary pattern scores were strongly and positively associated with DRIs-scores (in men: ρ = 0.806, p < 0.001; in women: ρ = 0.868, p < 0.001), and the DRIs-scores reached a plateau around the highest tertile of the healthy dietary pattern score. These results indicate that a healthy Japanese dietary pattern is associated with adequate micronutrient intakes based on the DRIs-J 2015 in both men and women.

Determination of the Kinetic Parameters for 123I Uptake by the Thyroid, Thyroid Weights, and Thyroid Volumes in Present-day Healthy Japanese Volunteers.

The purpose of this study was to evaluate the kinetic parameters that determine the uptake rate of radioiodide in the thyroid over 24 h after administration and to estimate thyroid volumes/masses of present-day Japanese. Methods: We determined the thyroid uptake rate of I in healthy male Japanese after oral administration (4.5-8.0 MBq) without iodine restriction. Masses of thyroid glands were collected in 2012-2016 during autopsies of 7,651 male and 3,331 female subjects. Volumes of thyroid glands were estimated by ultrasonography and magnetic resonance imaging in 52 male subjects. Results: The thyroid uptake rate of I for 24 h was 16.1 ± 5.4%. Kinetic model analysis was conducted to obtain the clearances (L h) for thyroid uptake and urinary excretion of I (0.499 ± 0.258 and 2.10 ± 0.39 L h, respectively). The masses of thyroid glands were on average 19.8 g (95% confidence interval of 18.3-19.5 g) and 15.5 g (95% confidence interval of 14.7-16.2 g) in male and female subjects aged 19-52 y, respectively. Volumes of thyroid glands estimated by ultrasonography and magnetic resonance imaging were 17.5 ± 5.2 and 14.2 ± 5.3 mL, respectively. In healthy Japanese, there has been no significant change for at least 50 y in the thyroid uptake of radioiodide over 24 h or in its kinetic parameters. These Japanese-specific kinetic parameters will allow quantitative estimation of the radiation exposure from the Fukushima accident and its variance during the individual's evacuation from or stay in Fukushima.

Prevalence Rate and Predictive Factors of Pancreatic Diseases in Cases with Pancreatic Duct Dilatation: A Cross-sectional Study of a Large, Healthy Japanese Population.

Objectives To clarify the significance of ultrasonographically recorded pancreatic duct dilatation. Methods Various parameters predicting pancreatic disease were evaluated in relation to pancreatic duct dilatation using data from medical checkups of healthy examinees. Results Records of 281,384 subjects were analyzed. Pancreatic duct dilatation (≥3 mm) was determined ultrasonographically in 524 patients (0.19%). Subsequent detailed examinations revealed the presence of pancreatic disease in 24.8% of these patients, including pancreatic cysts (15.6%) and chronic pancreatitis (4.9%). Pancreatic cancer was found in 6 cases (1.3%). Predictive factors of pancreatic diseases in examinees with pancreatic duct dilatation were investigated, and the diameter of the pancreatic duct (p<0.001) and HbA1c (p=0.003) were identified by a multivariate analysis. The diameter of the pancreatic duct (p<0.013), HbA1c (p=0.009), and body mass index (p=0.032) were identified as predictive factors in pancreatic cancer. The diameter of the pancreatic duct (p<0.001), age (p=0.006), and bilirubin (p=0.020) in pancreatic cyst as well as the diameter of the pancreatic duct (p<0.001), white blood cells (p=0.022), HbA1c (p=0.033), and alkaline phosphatase (p=0.043) in chronic pancreatitis were also identified. In patients with pancreatic duct dilatation, the optimal cut-off values were 3.5 mm and 6.1% for the pancreatic duct diameter and age, respectively, based on a receiver operating characteristic analysis. Conclusion In cases with ultrasonography-determined pancreatic duct dilatation, subsequent detailed examinations of the pancreas were necessary because of the high-prevalence rate of 24.8%. In particular, marked pancreatic duct dilatation (≥3.5 mm) and elevated HbA1c (≥6.1%) strongly suggest the presence of pancreatic diseases.

A Phase I, Open-Label Trial to Assess the Absorption, Metabolism, and Excretion of (14C)-OPC-61815 in Healthy Male Japanese Subjects

A Phase I, Open-Label Trial to Assess the Absorption, Metabolism, and Excretion of (14C)-OPC-61815 in Healthy Male Japanese Subjects

Consumption of a meal containing refined barley flour bread is associated with a lower postprandial blood glucose concentration after a second meal compared with one containing refined wheat flour bread in healthy Japanese: A randomized control trial.

Foods reducing postprandial hyperglycemia could suppress the postprandial blood glucose response after the next meal (a "second-meal" effect). However, the second-meal effect of refined barley flour bread has not been evaluated. The aim of this study is to determine whether consumption of refined barley flour bread reduces postprandial glucose concentrations after this and the subsequent meal. We enrolled 23 healthy young Japanese adults and conducted a randomized, double-blind, placebo-controlled, crossover study. The participants consumed refined barley flour bread containing 2.5 g β-glucan or refined wheat flour bread in a first meal, then consumed three rice balls as a second meal. Their postprandial blood glucose concentrations were measured 0, 15, 30, 45, 60, 90, and 120 min after both meals. Participants with fasting glucose concentrations above the diagnostic threshold for diabetes were excluded. The blood glucose concentration 30 min after the first meal was significantly lower (P < 0.05) if refined barley flour bread (7.1 ± 1.0 mmol/L) rather than refined wheat flour bread (7.7 ± 1.2 mmol/L) was consumed. Significantly lower glucose concentrations after the second meal measured at 60 (P < 0.05, barley flour bread: 8.7 ± 1.8 mmol/L, wheat flour bread: 9.3 ± 1.7 mmol/L) and 90 min (P < 0.01, barley flour bread: 7.8 ± 1.4 mmol/L, wheat flour bread: 8.8 ± 2.1 mmol/L) were lower in participants who had previously consumed the refined barley flour bread. Consumption of bread made with refined barley flour lowers postprandial blood glucose concentration after this and a subsequent meal compared with the consumption of refined wheat flour bread in healthy young Japanese adults.

A Study to Evaluate AG-881 in Healthy Japanese and Non-Asian Participants

A Study to Evaluate AG-881 in Healthy Japanese and Non-Asian Participants

Being Conscious of Water Intake Positively Associated with Sufficient Non-Alcohol Drink Intake Regardless of Seasons and Reasons in Healthy Japanese; the KOBE Study: A Cross Sectional Study.

The present study sought to clarify if being conscious of water intake (CWI) is associated with sufficient non-alcohol drink (NAD) intake. We used data of healthy participants without diabetes, aged 40–74 years, in the Kobe Orthopedic and Biomedical Epidemiologic (KOBE) study. The association between being CWI and NAD intake was evaluated by multivariate linear regression analyses after adjusting for age, sex, surveyed months (seasons), alcohol drinking, health-awareness life habits, socioeconomic factors, serum osmolarity, estimated daily salt intake, and reasons for NAD intake. Among 988 (698 women and 290 men) participants eligible for the present analyses, 644 participants (65.2%) were CWI and 344 participants (34.8%) were not CWI (non-CWI). The most popular reason for being CWI was to avoid heat stroke in summer and to prevent ischemic cerebral stroke in winter. The CWI group took more NAD, especially decaffeinated beverages, than the non-CWI group (1846.7 ± 675.1 mL/day vs. 1478.0 ± 636.3 ml/day, p < 0.001). There was a significant association between being CWI and NAD intake in multivariate linear regression analyses ever after adjusting for the relevant variables (β = 318.1, p < 0.001). These findings demonstrated CWI, regardless of the reasons and the seasons, was associated with high NAD intake in Japanese healthy population.

Draft Genome Sequences of Enterococcus faecalis Strains Isolated from Healthy Japanese Individuals.

Enterococcus faecalis is a common commensal of the intestines of humans and other mammals but is also a frequent cause of serious ailments. Here, we report 14 draft genome sequences of strains of Enterococcus faecalis, a normal inhabitant and Gram-positive bacterium that was isolated from 7 healthy Japanese volunteers.

Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB104 in Healthy Japanese and Non-Japanese Participants

Study to Assess the Safety, Tolerability, and Pharmacokinetics of BIIB104 in Healthy Japanese and Non-Japanese Participants

A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants

A Study to Test the Safety, and Tolerability of Padsevonil in Healthy Male Japanese Study Participants

Single Oral Dose of 4 mg Cenerimod in Healthy Japanese and Caucasian Subjects

Single Oral Dose of 4 mg Cenerimod in Healthy Japanese and Caucasian Subjects

Pharmacokinetics and Bioequivalence of Memantine Tablet and a New Dry Syrup Formulation in Healthy Japanese Males: Two Single-Dose Crossover Studies.

IntroductionMemantine hydrochloride, an N-methyl-D-aspartate receptor antagonist, is used to treat Alzheimer’s disease (AD). A new dry syrup formulation containing memantine hydrochloride has been developed to improve medication adherence in AD patients and to reduce family and caregiver burden. This study was conducted to assess the bioequivalence of this new formulation to the tablet.MethodsTwo single-dose, randomized, open-label, two-period, two-group, crossover studies were conducted to assess the bioequivalence of a test product [dry syrup, 2%, 1 g (containing 20 mg of memantine hydrochloride)] to a reference product (film-coated tablet) under two dosing conditions: administration of the test product as a suspension in water (Study I) and as granules taken with water (Study II). Blood samples were collected at specified time intervals, and memantine plasma concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The pharmacokinetic parameters of memantine were calculated using non-compartmental analysis. The maximum concentration (Cmax) and area under the concentration–time curve up to the last sampling time (AUCall) were used to assess the bioequivalence of the two formulations.ResultsThe geometric least square mean (GLSM) ratios [90% confidence interval (CI)] of the Cmax and AUCall of memantine for the test product to the reference product were 0.981 (0.943–1.020) and 0.978 (0.955–1.001) in Study I, and 0.973 (0.944–1.003) and 1.004 (0.983–1.025) in Study II, respectively. In both studies, the 90% CI values of the GLSM ratios of Cmax and AUCall were within the prespecified bioequivalence range (0.80–1.25). The safety of the test product under both dosing conditions and that of the reference product were not different.ConclusionsThe new dry syrup formulation containing memantine hydrochloride showed bioequivalence to the film-coated tablet under the two dosing conditions. Thus, the new dry syrup is suitable under either dosing condition for patients with AD.FundingDaiichi Sankyo Co., Ltd.

Thermolabile polymorphism of carnitine palmitoyltransferase 2: A genetic risk factor of overall acute encephalopathy

ObjectivesAcute encephalopathy is an acute brain dysfunction after preceding infection, consisting of multiple syndromes. Some syndromes, such as acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), are severe with poor outcome, whereas others, such as clinically mild encephalitis/encephalopathy with reversible splenial lesion (MERS), are mild with favorable outcome. Previous study reported the association of the thermolabile polymorphism in Carnitine Palmitoyltransferase 2 (CPT2) gene and severe syndromes of acute encephalopathy. To further explore the pathogenetic role of CPT2 in acute encephalopathy, we conducted a case-control association study of a typical thermolabile CPT2 polymorphism, rs2229291, in 416 patients of acute encephalopathy, including both severe and mild syndromes. MethodsThe case cohort consisted of 416 patients, including AESD, MERS, and other syndromes. The control subjects were 100 healthy Japanese. rs2229291 was genotyped by Sanger sequencing. Genetic distribution was compared between the patients and controls using Cochran-Armitage trend test. ResultsMinor allele frequency of rs2229291 was significantly higher in AESD (p = 0.044), MERS (p = 0.015) and entire acute encephalopathy (p = 0.044) compared to the controls. The polymorphism showed no significant association with influenza virus, or with outcome. ConclusionsThis study provided evidence that CPT2 is a susceptibility gene for overall acute encephalopathy, including both severe and mild syndromes, and suggested that impairment of mitochondrial metabolism is common to various syndromes of acute encephalopathy.

The Association Between the Serum Uric Acid to Creatinine Ratio and Metabolic Syndrome, Liver Function, and Alcohol Intake in Healthy Japanese Subjects.

Background: In patients with diabetes mellitus, the serum uric acid (UA) to creatinine (Cr) ratio (UA/Cr) has been reported to be associated with a higher risk of metabolic syndrome (MetS). In healthy subjects, however, this relationship and a possible association with pathological conditions remain undetermined. Methods: In total, 9104 Japanese subjects who had undergone an annual health examination and who were not receiving medication were divided into four groups based on UA/Cr values, and various markers were compared. Results: Anthropometric measures, blood pressure, glycemic state, lipids [except high-density lipoprotein cholesterol (HDL-C)], renal function, transaminases, and numbers of MetS components increased, according to UA/Cr quartiles, as the UA/Cr increased. In contrast, HDL-C and Cr decreased as the UA/Cr increased. UA/Cr values increased as the number of MetS increased. When UA/Cr values within each alcohol consumption group were investigated, the overall metabolic profile was the worst in subjects who consumed ≥75 grams ethanol a day with a UA/Cr of ≥6.8, except for fasting immunoreactive insulin (FIRI), homeostasis model assessment of insulin resistance (HOMA-IR), low-density lipoprotein cholesterol (LDL-C), and HDL-C values. Subjects who did not consume alcohol with a UA/Cr of ≥6.8 showed the highest FIRI, HOMA-IR, and LDL-C values. Conclusions: The UA/Cr was associated with components of MetS, liver function, and alcohol intake in healthy Japanese subjects. The UA/Cr might be a useful marker to distinguish subjects with high IR and dyslipidemia who do not consume alcohol.