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1.  Effect of Hemodialysis on Plasma Glucose Profile and Plasma Level of Liraglutide in Patients with Type 2 Diabetes Mellitus and End-Stage Renal Disease: A Pilot Study 
PLoS ONE  2014;9(12):e113468.
The effect of hemodialysis on the plasma glucose profile and liraglutide level after liraglutide injection was investigated in patients with diabetes and end-stage renal disease (ESRD). Either 0.6 mg or 0.9 mg liraglutide was subcutaneously administered daily to 10 Japanese type 2 diabetic patients with ESRD. Hemodialysis was conducted on days 1 and 3. Plasma liraglutide and glucose concentrations were measured by enzyme-linked immunosorbent assay and a continuous glucose monitoring system, respectively. The safety profile of liraglutide was also assessed. Hemodialysis had no effect on the pharmacokinetic parameters of liraglutide in patients with diabetes and ESRD; the maximum plasma concentration (Cmax), tmax, area under the concentration-time curve (AUC), and CL/f were unaltered. Similarly, hemodialysis did not affect the mean or minimum glucose levels, AUC, or duration of hyperglycemia (>180 mg/dL) and hypoglycemia (<70 mg/dL) following liraglutide administration. However, significant increases in mean amplitude of glycemic excursions (MAGE) and standard deviation (SD) as markers of glucose fluctuation, and the maximum glucose level were observed during hemodialysis. No adverse events, including hypoglycemia, were observed after liraglutide injection, either off-hemodialysis (day 2) or on-hemodialysis (day 3). Liraglutide was well tolerated in patients with type 2 diabetes and ESRD undergoing hemodialysis. The present results suggested that hemodialysis did not affect the pharmacokinetic profile of liraglutide or most glycemic indices, with the exception of MAGE, SD, and the maximum glucose level. These results suggested that it may be possible to use liraglutide during hemodialysis for diabetes with ESRD, without dose adjustment.
Trial Registration UMIN Clinical Trials Registry (UMIN-CTR) UMIN000010159
PMCID: PMC4272272  PMID: 25526642
2.  Protocol for a large-scale prospective observational study with alogliptin in patients with type 2 diabetes: J-BRAND Registry 
BMJ Open  2014;4(9):e004760.
Dipeptidyl peptidase-4 (DPP-4) inhibitors including alogliptin are categorised as a newer class of oral hypoglycaemic, antidiabetic drugs to suppress the degradation of incretin hormones ((glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) by DPP-4. We have scheduled a large-scale, multicentre, prospective, observational study (Japan-Based clinical ReseArch Network for Diabetes Registry: J-BRAND Registry) to construct an extensive database over a long-term clinical course in patients with type 2 diabetes receiving oral hypoglycaemic agents (OHAs) and to evaluate the safety and efficacy of alogliptin in Japanese population.
Methods and analysis
20 000 patients with type 2 diabetes will be registered into two groups of 10 000 each: group A patients will be treated with alogliptin, while group B patients will be treated with non-DPP-4 inhibitor OHA(s). Approximately 300 institutions nationwide will enrol and assign eligible patients equally to either group. Each patient's data will be collected every 6 months for a 3-year period, during which time treatment with OHA(s) may be changed or discontinued, as per package insert for each OHA. Primary end points are safety variables to be compared between the two groups and their subgroups, with respect to hypoglycaemia, pancreatitis, skin disorders, infections and cancer. Secondary end points are efficacy variables including from-baseline changes of A1c, fasting glucose, fasting insulin and urinary albumin, which will be compared between groups/subgroups. New onset and progression of microangiopathy will also be evaluated against OHA(s). Overall, the J-BRAND Registry will evaluate the safety and efficacy of antidiabetic OHA(s) including alogliptin, based on a large-scale database.
Ethics and dissemination
This study will be conducted with the highest respect for individual participants according to this protocol, the Declaration of Helsinki, the Ethical Guidelines for Clinical Research (Japan Ministry of Health, Labour and Welfare, 2008) and relevant laws/regulations. The present study will construct a valuable database of patients with type 2 diabetes treated with OHA(s) including alogliptin.
Trial registration number
PMCID: PMC4166248  PMID: 25227623
type 2 diabetes; DPP-4 inhibitor; alogliptin; observational study
3.  Abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan: a cross-sectional study 
BMC Pediatrics  2014;14:81.
There are a limited number of studies regarding the association between abdominal obesity and serum adiponectin complexes (high, medium, and low molecular weight adiponectins) among population-based elementary school children, especially in Japan, where blood collection is not usually performed during annual health examinations of school children. The aim of the present study was to investigate the relationship between abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan.
Subjects were all the fourth-grade school children (9 or 10 years of age) in the town of Ina during 2005–2008 (N = 1675). The height, weight, percent body fat, and waist circumference (WC) of each subject were measured. Blood samples were drawn from subjects to measure adiponectin isoform values. Childhood abdominal obesity was defined as “a waist-to-height ratio greater than or equal to 0.5” or “a WC greater than or equal to 75 cm”. The Wilcoxon rank-sum test and the logistic regression model were used to analyze the association between abdominal obesity and each adiponectin isoform value.
Data from 1654 subjects (846 boys and 808 girls) were analyzed. Adiponectin complexes were lower in the abdominal obesity group than in the non-abdominal obesity group regardless of sex. Abdominal obesity significantly increased the odds ratio (OR) for each adiponectin isoform level less than or equal to the median value in boys; the OR (95% confidence interval [CI]) was 2.50 (1.59-3.92) for high molecular weight adiponectin (HMW-adn), 2.47 (1.57-3.88) for medium molecular weight adiponectin (MMW-adn), and 1.75 (1.13-2.70) for low molecular weight adiponectin (LMW-adn). In girls, the OR (95% CI) was 1.95 (1.18-3.21) for HMW-adn, 1.40 (0.86-2.28) for MMW-adn, and 1.06 (0.65-1.70) for LMW-adn.
Abdominal obesity was associated with lower adiponectin complexes and the influence of abdominal obesity varied by adiponectin isoform. Furthermore, the impact of abdominal obesity was larger in boys than in girls. The present study results suggest that prevention of abdominal obesity could contribute to the prevention of lower adiponectin levels, especially in boys.
PMCID: PMC3986877  PMID: 24670108
Abdominal obesity; Serum adiponectin complexes; School children; Population-based epidemiological study
4.  Long-Term Mortality in Nationwide Cohorts of Childhood-Onset Type 1 Diabetes in Japan and Finland 
Diabetes care  2003;26(7):2037-2042.
This study compares mortality from type 1 diabetes in Japan and Finland and examines the effects of sex, age at diagnosis, and calendar time period of diagnosis on mortality.
Research Design and Methods
Patients with type 1 diabetes from Japan (n = 1,408) and Finland (n = 5,126), diagnosed from 1965 through 1979, at age <18 years, were followed until 1994. Mortality was estimated with and without adjustment for that of the general population to assess absolute and relative mortality using Cox proportional hazard models.
Overall mortality rates in Japan and Finland were 607 (95% CI 510–718) and 352 (315–393), respectively, per 100,000 person-years; standardized mortality ratios were 12.9 (10.8–15.3) and 3.7 (3.3–4.1), respectively. Absolute mortality was higher for men than for women in Finland, but relative mortality was higher for women than for men in both cohorts. Absolute mortality was higher in both cohorts among those whose diabetes was diagnosed during puberty, but relative mortality did not show any significant difference by age at diagnosis in either cohort. In Japan, both absolute and relative mortality were higher among those whose diagnosis was in the 1960s rather than the 1970s.
Mortality from type 1 diabetes was higher in Japan compared with Finland. The increased risk of death from type 1 diabetes seems to vary by sex, age at diagnosis, and calendar time period of diagnosis. Further investigation, especially on cause-specific mortality, is warranted in the two countries.
PMCID: PMC3752687  PMID: 12832309
5.  24-Hour Glycemic Variations in Drug-Naïve Patients with Type 2 Diabetes: A Continuous Glucose Monitoring (CGM)-Based Study 
PLoS ONE  2013;8(7):e71102.
To investigate a 24-hour glycemic variation in drug-naïve, type 2 diabetic patients by using CGM.
A total of 30 inpatients with type 2 diabetes were included in the study to analyze the 24-hour CGM data.
The patients’ median age was 58 years old (interquartile range: 42–66 years), and their median HbA1c value was 7.6 (6.7–8.8)%. The median time to postprandial peak glucose levels(Peak Time) for each meal was 70–85 minutes, with the range of postprandial glucose increases(Increase Range) for each meal being 83–109 mg/dL. There was a significant positive correlation between the HbA1c values and Increases Range, Peak Time observed after breakfast and dinner, respectively. When the patients were stratified by a median HbA1c value of 7.6% into 2 groups, Increases Range and Peak Time, after breakfast, were shown to be significantly higher in the high-HbA1c group (H) than in the low-HbA1c (L) group. When the subjects were divided into four groups according to HbA1c levels:1 (<7.0%, n = 8), 2 (7.0–7.9%, n = 8), 3 (8.0–8.9%, n = 8), and 4 (≥9%, n = 6), the average glucose level, pre-meal glucose level and postprandial peak glucose level increased steadily from group 1 to 4 in a stepwise manner.
In drug-naïve, Japanese type 2 diabetic patients, the Peak Time and the Increase Range were maximal after dinner. It was shown that the greater the HbA1c values, the longer Peak time and the higher Increase Range after breakfast and dinner. The average glucose level, pre meal glucose level and postprandial peak glucose level increased steadily as HbA1c level increased.
PMCID: PMC3728307  PMID: 23936258
6.  Eating Behaviors and Overweight among Adolescents: A Population-Based Survey in Japan 
Journal of Obesity  2013;2013:717942.
Objectives. The aim of the present study was to investigate the relationship between eating behaviors and overweight among population-based adolescents in Japan. Methods. Study subjects comprised adolescents in the seventh grade (age range, 12–13 years) from Ina, a town in Saitama Prefecture, Japan, between 1999 and 2008. The height and weight of the subjects were measured, and information concerning eating behaviors (eating speed and eating until full) was obtained using a self-administered questionnaire. Results. Among boys (n = 1586), fast eating speed significantly increased the odds ratio (OR) for overweight when compared with medium eating speed, regardless of eating until full or not; moreover, a more marked increase in the OR was observed among boys eating until full (OR: 2.78, 95% confidence interval: 1.76–4.38) than among those not eating until full (2.43, 1.41–4.20). Among girls (n = 1542), fast eating speed led to a significant increase in the OR in those eating until full; however, no significant increases were observed in the OR in those eating quickly and not until full. Conclusions. Among adolescents, fast eating speed was associated with overweight; furthermore, the combination of both fast eating speed and eating until full may have a significant effect on overweight.
PMCID: PMC3730185  PMID: 23956845
7.  LDL-cholesterol and body mass index among Japanese schoolchildren: a population-based cross-sectional study 
Serum low-density lipoprotein cholesterol (LDL-C) is one of the most important risk factors for coronary heart disease. The aim of the present study was to investigate the relationship between LDL-C and body mass index (BMI) in population-based Japanese schoolchildren.
The subjects comprised all fourth graders and seventh graders in Ina Town, Saitama Prefecture, Japan, during 2002-2009. Information about each subject’s age, sex, and family history of hypercholesterolemia was collected using a self-administered questionnaire. The body height, weight, and LDL-C were measured for each child. LDL-C was measured using the direct method. According to the LDL-C criteria of the Japan Atherosclerosis Society, LDL-C level was categorized into three subgroups: acceptable, < 110 mg/dL; borderline, 110-139 mg/dL; and high, ≥ 140 mg/dL. Children with either borderline or high LDL-C level were considered to have high-normal LDL-C (HLDL-C).
Data from a total of 5869 subjects were analyzed. A higher BMI category was associated with a higher prevalence of HLDL-C regardless of sex or grade level (P < 0.05). When compared with the <50th percentile BMI category, the odds ratio (OR) for HLDL-C was statistically significant in the 75th to 84th percentile category of fourth-grade boys (OR: 1.95, 95% confidence interval (95% CI): 1.28-2.97), the 85th to 94th percentile of fourth-grade girls (2.52, 1.74-3.64), and the 85th to 94th percentile of seventh-grade boys (2.04, 1.31-3.20) and girls (1.90, 1.24-2.91).
A statistically significant association between LDL-C levels and BMI was observed in Japanese school children.
PMCID: PMC3680021  PMID: 23705977
Serum low-density lipoprotein; Body mass index; Schoolchildren
8.  Interactions between Serum Vitamin D Levels and Vitamin D Receptor Gene FokI Polymorphisms for Renal Function in Patients with Type 2 Diabetes 
PLoS ONE  2012;7(12):e51171.
We aimed to examine associations among serum 25-hydroxyvitamin D (25OHD) levels, 1,25-dihyroxyvitamin D (1,25OHD) levels, vitamin D receptor (VDR) polymorphisms, and renal function based on estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes.
In a cross-sectional study of 410 patients, chronic kidney disease (CKD) stage assessed by eGFR was compared with 25OHD, 1,25OHD, and VDR FokI (rs10735810) polymorphisms by an ordered logistic regression model adjusted for the following confounders: disease duration, calendar month, use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers or statins, and serum calcium, phosphate, and intact parathyroid hormone levels.
1,25OHD levels, rather than 25OHD levels, showed seasonal oscillations; peak levels were seen from May to October and the lowest levels were seen from December to February. These findings were evident in patients with CKD stage 3∼5 but not stage 1∼2. eGFR was in direct proportion to both 25OHD and 1,25OHD levels (P<0.0001), but it had stronger linearity with 1,25OHD (r = 0.73) than 25OHD (r = 0.22) levels. Using multivariate analysis, 1,25OHD levels (P<0.001), but not 25OHD levels, were negatively associated with CKD stage. Although FokI polymorphisms by themselves showed no significant associations with CKD stage, a significant interaction between 1,25OHD and FokITT was observed (P = 0.008). The positive association between 1,25OHD and eGFR was steeper in FokICT and CC polymorphisms (r = 0.74) than FokITT polymorphisms (r = 0.65).
These results suggest that higher 1,25OHD levels may be associated with better CKD stages in patients with type 2 diabetes and that this association was modified by FokI polymorphisms.
PMCID: PMC3514263  PMID: 23226566
9.  Number of siblings, birth order, and childhood overweight: a population-based cross-sectional study in Japan 
BMC Public Health  2012;12:766.
Although several studies have investigated the relationship between the number of siblings or birth order and childhood overweight, the results are inconsistent. In addition, little is known about the impact of having older or younger siblings on overweight among elementary schoolchildren. The present population-based study investigated the relationship of the number of siblings and birth order with childhood overweight and evaluated the impact of having younger or older siblings on childhood overweight among elementary schoolchildren in Japan.
Subjects comprised fourth-grade schoolchildren (age, 9–10 years) in Ina Town during 1999–2009. Information about subjects’ sex, age, birth weight, birth order, number of siblings, lifestyle, and parents’ age, height, and weight was collected by a self-administered questionnaire, while measurements of subjects’ height and weight were done at school. Childhood overweight was defined according to age- and sex-specific cut-off points proposed by the International Obesity Task Force. A logistic regression model was used to calculate the odds ratio (OR) and 95% confidence intervals (95% CI) of "number of siblings" or "birth order" for overweight.
Data from 4026 children were analyzed. Only children (OR: 2.13, 95% CI: 1.45-3.14) and youngest children (1.56, 1.13-2.16) significantly increased ORs for overweight compared with middle children. A larger number of siblings decreased the OR for overweight (P for trend < 0.001). Although there was no statistically significant relationship between a larger number of older siblings and overweight, a larger number of younger siblings resulted in a lower OR for overweight (P for trend < 0.001).
Being an only or youngest child was associated with childhood overweight, and having a larger number of younger siblings was negatively associated with overweight. The present study suggests that public health interventions to prevent childhood overweight need to focus on children from these family backgrounds.
PMCID: PMC3509397  PMID: 22966779
Sibling; Birth-order; Childhood overweight; Public health
10.  High-molecular-weight adiponectin and anthropometric variables among elementary schoolchildren: a population-based cross-sectional study in Japan 
BMC Pediatrics  2012;12:139.
Studies about the relationship between high-molecular-weight adiponectin (HMW-adn) and anthropometric variables among population-based elementary schoolchildren have been too limited, especially in Japan, where blood collection is not usually performed in the annual health examination at elementary schools. The objective of the present study was to investigate the relationship between HMW-adn and anthropometric variables (body mass index [BMI], percent body fat [%BF], waist circumference [WC], and waist-to-height ratio [WHtR]) among population-based elementary schoolchildren in Japan.
Subjects comprised all fourth-grade schoolchildren (9 or 10 years of age) in the town of Ina, Saitama Prefecture, Japan during 2005–2008 (N = 1675). After excluding 21 subjects because of refusal to participate or incomplete data, data from a total of 1654 subjects (846 boys and 808 girls) were analyzed. The height, weight, %BF, and WC of each subject were measured, while blood samples were drawn from the subjects to measure adiponectin levels (HMW-adn and total adiponectin). Childhood obesity was determined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman’s correlation coefficients between adiponectin levels and anthropometric variables were calculated for each sex.
The anthropometric variables were negatively correlated with HMW-adn in both boys and girls. Correlation coefficients of HMW-adn with anthropometric variables in the obesity group were consistently higher than those in the non-obesity group among both boys and girls. In addition, only WHtR was significantly correlated with HMW-adn regardless of sex and physique (obesity or non-obesity); the correlation coefficient was -0.386 among boys and -0.543 among girls in the obesity group, while it was -0.124 among boys and -0.081 among girls in the non-obesity group.
HMW-adn was negatively correlated with anthropometric variables, while the correlation coefficients of HMW-adn with anthropometric variables in the obesity group were consistently higher than those in the non-obesity group. Moreover, only WHtR was significantly associated with HMW-adn regardless of sex and physique. The results of this study suggested that it is useful to monitor WHtR as a surrogate for HMW-adn among elementary school students, especially obese children.
PMCID: PMC3478987  PMID: 22937905
High-molecular-weight adiponectin; Anthropometric variable; Obesity; Waist-to-height ratio; Children
11.  Comparison of vildagliptin twice daily vs. sitagliptin once daily using continuous glucose monitoring (CGM): Crossover pilot study (J-VICTORIA study) 
No previous studies have compared the DPP-4 inhibitors vildagliptin and sitagliptin in terms of blood glucose levels using continuous glucose monitoring (CGM) and cardiovascular parameters.
Twenty patients with type 2 diabetes mellitus were randomly allocated to groups who received vildagliptin then sitagliptin, or vice versa. Patients were hospitalized at 1 month after starting each drug, and CGM was used to determine: 1) mean (± standard deviation) 24-hour blood glucose level, 2) mean amplitude of glycemic excursions (MAGE), 3) fasting blood glucose level, 4) highest postprandial blood glucose level and time, 5) increase in blood glucose level after each meal, 6) area under the curve (AUC) for blood glucose level ≥180 mg/dL within 3 hours after each meal, and 7) area over the curve (AOC) for daily blood glucose level <70 mg/dL. Plasma glycosylated hemoglobin (HbA1c), glycoalbumin (GA), 1,5-anhydroglucitol (1,5AG), immunoreactive insulin (IRI), C-peptide immunoreactivity (CPR), brain natriuretic peptide (BNP), and plasminogen activator inhibitor-1 (PAI-1) levels, and urinary CPR levels, were measured.
The mean 24-hour blood glucose level was significantly lower in patients taking vildagliptin than sitagliptin (142.1 ± 35.5 vs. 153.2 ± 37.0 mg/dL; p = 0.012). In patients taking vildagliptin, MAGE was significantly lower (110.5 ± 33.5 vs. 129.4 ± 45.1 mg/dL; p = 0.040), the highest blood glucose level after supper was significantly lower (206.1 ± 40.2 vs. 223.2 ± 43.5 mg/dL; p = 0.015), the AUC (≥180 mg/dL) within 3 h was significantly lower after breakfast (484.3 vs. 897.9 mg/min/dL; p = 0.025), and urinary CPR level was significantly higher (97.0 ± 41.6 vs. 85.2 ± 39.9 μg/day; p = 0.008) than in patients taking sitagliptin. There were no significant differences in plasma HbA1c, GA, 1,5AG, IRI, CPR, BNP, or PAI-1 levels between patients taking vildagliptin and sitagliptin.
CGM showed that mean 24-h blood glucose, MAGE, highest blood glucose level after supper, and hyperglycemia after breakfast were significantly lower in patients with type 2 diabetes mellitus taking vildagliptin than those taking sitagliptin. There were no significant differences in BNP and PAI-1 levels between patients taking vildagliptin and sitagliptin.
Trial registration
PMCID: PMC3471040  PMID: 22867630
Vildagliptin; Sitagliptin; Continuous glucose monitoring (CGM); Brain natriuretic peptide (BNP); Plasminogen activator inhibitor-1 (PAI-1)
12.  Eating Behavior and Childhood Overweight Among Population-Based Elementary Schoolchildren in Japan  
This study investigated the relationship between eating behavior and childhood overweight among population-based elementary schoolchildren in Japan. Data was collected from fourth graders (9 or 10 years of age) from Ina Town, Saitama Prefecture, Japan from 1999 to 2009. Information about subjects’ sex, age, and lifestyle, including eating behaviors (eating until full and chewing thoroughly), was obtained using a self-administered questionnaire, and height and weight were measured directly. Overweight was determined according to the definition established by the International Obesity Task Force. Data from 4027 subjects (2079 boys and 1948 girls) were analyzed. Chewing thoroughly was associated with a significantly decreased odds ratio (OR) for being overweight, whereas eating until full significantly increased the OR for being overweight (OR: 1.50, 95% confidence interval: 1.16–1.94) among boys. However, eating until full was not associated with a significantly increased OR for being overweight among the group that reported chewing thoroughly, whereas it was associated with a significantly increased OR for being overweight (2.02, 1.38–2.94) among boys who did not chew thoroughly. In conclusion, eating until full or not chewing thoroughly was associated with being overweight among elementary schoolchildren. Results of this study suggest that chewing thoroughly may be an avenue to explore childhood overweight prevention efforts.
PMCID: PMC3366619  PMID: 22690201
eating behavior; overweight; children; eating until full; chewing
13.  Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial 
Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.
In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for >5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up <6.0%, 6.0%-<6.5%, or ≥6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.
Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c ≥6.5% versus <6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p <0.01 and HR, 3.0; p <0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p <0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.
In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.
PMCID: PMC3150244  PMID: 21714932
Hemoglobin A1c (HbA1c); cardiovascular disease (CVD); hypercholesterolemia; HMG CoA reductase inhibitor; pravastatin, MEGA Study
14.  High Blood Pressure in Obese and Nonobese Japanese Children: Blood Pressure Measurement is Necessary Even in Nonobese Japanese Children 
Journal of Epidemiology  2010;20(5):408-412.
Although the prevalences of obesity and hypertension (HT) are increasing in children, there have been few epidemiological studies of HT in Japanese children. We evaluated the prevalences of HT and high-normal blood pressure (HNBP), and examined the relationship between blood pressure (BP) and body mass index (BMI), in Japanese children.
The subjects of this study were 2420 children living in the town of Ina, Saitama Prefecture, Japan during the period from 2006 through 2008. Body height, weight, and BP were measured. HT and HNBP were defined according to the HT criteria for Japanese children. Children with HNBP or HT were defined as having high blood pressure (HBP).
The prevalences of HBP were 15.9% and 15.8% in fourth-grade boys and girls, respectively, and 11.1% and 10.8% in seventh-grade boys and girls, respectively. Irrespective of sex or grade level, a higher BMI was associated with a higher prevalence of HBP (P < 0.001). When compared with the <50th percentile BMI category, the crude odds ratios (ORs) were statistically significant for the 75th to 84th percentile category in fourth-grade boys (OR: 4.54, 95% CI: 2.36–8.76), the ≥95th percentile in fourth-grade girls (13.29, 5.93–29.77), the 85th to 94th percentile (3.16, 1.46–6.84) in seventh-grade boys, and the ≥95th percentile (7.96, 3.18–19.93) in seventh-grade girls.
BMI was associated with HBP in Japanese school children. In addition, some children in the lower BMI categories also had HBP.
PMCID: PMC3900836  PMID: 20699600
high blood pressure; children; BMI; hypertensive family history
15.  Relationship of body mass index to percent body fat and waist circumference among schoolchildren in Japan - the influence of gender and obesity: a population-based cross-sectional study 
BMC Public Health  2010;10:493.
Although the correlation coefficient between body mass index (BMI) and percent body fat (%BF) or waist circumference (WC) has been reported, studies conducted among population-based schoolchildren to date have been limited in Japan, where %BF and WC are not usually measured in annual health examinations at elementary schools or junior high schools. The aim of the present study was to investigate the relationship of BMI to %BF and WC and to examine the influence of gender and obesity on these relationships among Japanese schoolchildren.
Subjects included 3,750 schoolchildren from the fourth and seventh grade in Ina-town, Saitama Prefecture, Japan between 2004 and 2008. Information about subject's age, sex, height, weight, %BF, and WC was collected from annual physical examinations. %BF was measured with a bipedal biometrical impedance analysis device. Obesity was defined by the following two criteria: the obese definition of the Centers for Disease Control and Prevention, and the definition of obesity for Japanese children. Pearson's correlation coefficients between BMI and %BF or WC were calculated separately for sex.
Among fourth graders, the correlation coefficients between BMI and %BF were 0.74 for boys and 0.97 for girls, whereas those between BMI and WC were 0.94 for boys and 0.90 for girls. Similar results were observed in the analysis of seventh graders. The correlation coefficient between BMI and %BF varied by physique (obese or non-obese), with weaker correlations among the obese regardless of the definition of obesity; most correlation coefficients among obese boys were less than 0.5, whereas most correlations among obese girls were more than 0.7. On the other hand, the correlation coefficients between BMI and WC were more than 0.8 among boys and almost all coefficients were more than 0.7 among girls, regardless of physique.
BMI was positively correlated with %BF and WC among Japanese schoolchildren. The correlations could be influenced by obesity as well as by gender. Accordingly, it is essential to consider gender and obesity when using BMI as a surrogate for %BF and WC for epidemiological use.
PMCID: PMC2933721  PMID: 20716379
16.  Continuous glucose monitoring with Humalog Mix 25 versus Humalog Mix 50, twice daily: A comparative pilot study -Results from the Jikei-EValuation of insulin Lispro mixture on pharmacodynamics and glycemic VariancE (J-EVOLVE) study 
To evaluate glycemic variability associated with two different premixed insulin analogue formulations when used in a twice-daily regimen.
Patients and Methods
Subjects comprised type 2 diabetic patients aged 20-79 years, treated with twice daily premixed insulin or insulin analogue formulations. All subjects were hospitalized for 6 days and randomized to receive either Humalog Mix 25 (Mix 25) or Humalog Mix 50 (Mix 50). They were then crossed over to the other arm between day 3 and day 4 of the study. Continuous glucose monitoring (CGM) was performed on all subjects to examine the differences in glycemic variability.
Eleven type 2 diabetic patients were enrolled. No significant difference was found in 24-hour mean glucose values and their SDs, pre-meal glucose values, increases from pre-meal to peak glucose values, or time to peak glucose levels between either group. However, the mean glucose values observed during 0-8 hrs were significantly lower with Mix 25 compared to Mix 50 (128 vs. 147 mg/dL; p = 0.024).
The twice-daily Mix 25 regimen provided superior overnight glycemic control compared to the Mix 50 regimen in Japanese patients with type 2 diabetes. However, both twice-daily regimens with either Mix 25 or Mix 50 provided inadequate post-lunch glycemic control.
Trial Registration
Current Controlled Trials UMIN000001327
PMCID: PMC2885326  PMID: 20438630
17.  Changes in body mass index, leptin and adiponectin in Japanese children during a three-year follow-up period: a population-based cohort study 
The study examined changes in and relationship between body mass index (BMI), leptin and adiponectin levels over a 3-year period in a pediatric population-based cohort.
Study design
A 3-year prospective cohort study of 268 boys and 251 girls aged 9–10 in Ina, Saitama, Japan.
Median body mass index (BMI) significantly increased from baseline (age 9–10) to follow up (age 12–13) in boys from 17.1 to 18.3 kg/m2 (P < 0.001) and in girls from 16.5 to 18.5 kg/m2 (P < 0.001), respectively. Adiponectin values significantly decreased from baseline to follow up in boys (13.5 to 8.9 μg/ml, respectively) (P < 0.001) and in girls (12.4 to 9.5 μg/ml, respectively) (P < 0.001). Leptin values at follow up significantly decreased from baseline in boys (4.9 to 2.3 ng/dl, respectively) (P < 0.001) and also in girls (5.3 to 5.1 ng/dl, respectively) (P = 0.049).
A relatively strong correlation was seen in BMI (Spearman's correlation coefficient, r = 0.864, P < 0.001 in boys; r = 0.873, P < 0.001 in girls), adiponectin (r = 0.705, P < 0.001 in boys; r = 0.695, P < 0.001 in girls), and leptin (r = 0.449, P < 0.001 in boys; r = 0.610, P < 0.001 in girls) before and after the three-year period.
The ratio of follow up to baseline BMI was negatively correlated with that for adiponectin (r = -0.224, P < 0.001 in boys; r = -0.165, P = 0.001 in girls) and positively correlated with that for leptin (r = 0.518, P < 0.001 in boys; r = 0.609, P < 0.001 in girls).
This study demonstrated that baseline adiponectin, leptin and BMI values measured at ages 9–10 correlated with those measured three years later. However, adiponectin values decreased and leptin values increased in those subjects whose BMI increased during over this period.
PMCID: PMC2701411  PMID: 19490650
18.  Prospective randomized study for optimal insulin therapy in type 2 diabetic patients with secondary failure 
The large clinical trials proved that Basal-Bolus (BB) insulin therapy was effective in the prevention of diabetic complications and their progression. However, BB therapy needs multiple insulin injections per a day. In this regard, a biphasic insulin analogue needs only twice-daily injections, and is able to correct postprandial hyperglycemia. Therefore it may achieve the blood glucose control as same as that of BB therapy and prevent the diabetic complications including macroangiopathy.
In PROBE (Prospective, Randomized, Open, Blinded-Endpoint) design, forty-two type 2 diabetic patients (male: 73.8%, median(inter quartile range) age: 64.5(56.8~71.0)years) with secondary failure of sulfonylurea (SU) were randomly assigned to BB therapy with a thrice-daily insulin aspart and once-daily basal insulin (BB group) or to conventional therapy with a twice-daily biphasic insulin analogue (30 Mix group), and were followed up for 6 months to compare changes in HbA1c, daily glycemic profile, intima-media thickness (IMT) of carotid artery, adiponectin levels, amounts of insulin used, and QOL between the two groups.
After 6 months, HbA1c was significantly reduced in both groups compared to baseline (30 Mix; 9.3(8.1~11.3) → 7.4(6.9~8.7)%, p < 0.01, vs BB;8.9(7.7~10.0) → 6.9(6.2~7.3)%, p < 0.01), with no significant difference between the groups in percentage change in HbA1c (30 Mix; -14.7(-32.5~-7.5)% vs BB -17.8(-30.1~-11.1)%, p = 0.32). There was a significant decrease in daily glycemic profile at all points except dinner time in both groups compared to baseline. There was a significant increase in the amount of insulin used in the 30 Mix group after treatment compared to baseline (30 Mix;0.30(0.17~0.44) → 0.39(0.31~0.42) IU/kg, p = 0.01). There was no significant difference in IMT, BMI, QOL or adiponectin levels in either group compared to baseline.
Both BB and 30 mix group produced comparable reductions in HbA1c in type 2 diabetic patients with secondary failure. There was no significant change in IMT as an indicator of early atherosclerotic changes between the two groups. The basal-bolus insulin therapy may not be necessarily needed if the type 2 diabetic patients have become secondary failure.
Trial registration
Current Controlled Trials number, NCT00348231
PMCID: PMC2442047  PMID: 18507868
19.  Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography 
Although oxidative stress by accumulation of reactive oxygen species (ROS) in diabetes has become evident, it remains unclear what genes, involved in redox balance, would determine susceptibility for development of atherosclerosis in diabetes. This study evaluated the effect of genetic polymorphism of enzymes producing or responsible for reducing ROS on coronary artery calcification in type 2 diabetes (T2D).
An index for coronary-arteriosclerosis, coronary artery calcium score (CACS) was evaluated in 91 T2D patients using a multi-slice computed tomography. Patients were genotyped for ROS-scavenging enzymes, Glutathione peroxidase-1 (GPx-1), Catalase, Mn-SOD, Cu/Zn-SOD, as well as SNPs of NADPH oxidase as ROS-promoting elements, genes related to onset of T2D (CAPN10, ADRB3, PPAR gamma, FATP4). Age, blood pressure, BMI, HbA1c, lipid and duration of diabetes were evaluated for a multivariate regression analysis.
CACS with Pro/Leu genotype of the GPx-1 gene was significantly higher than in those with Pro/Pro (744 ± 1,291 vs. 245 ± 399, respectively, p = 0.006). In addition, genotype frequency of Pro/Leu in those with CACS ≥ 1000 was significantly higher than in those with CACS < 1000 (45.5% vs. 18.8%; OR = 3.61, CI = 0.97–13.42; p = 0.045) when tested for deviation from Hardy-Weinberg's equilibrium. Multivariate regression analyses revealed that CACS significantly correlated with GPx-1 genotypes and age.
The presence of Pro197Leu substitution of the GPx-1 gene may play a crucial role in determining genetic susceptibility to coronary-arteriosclerosis in T2D. The mechanism may be associated with a decreased ability to scavenge ROS with the variant GPx-1.
PMCID: PMC2041944  PMID: 17825092
20.  New trends for practice in telecommunication applied to preventive and environmental medicine 
This paper presents survey results of connectivity to the Internet from preventive and environmental medicine-related departments in medical schools and other institutions in Japan and propose means to establish connectivity among them. Of 191 facilities surveyed, 134 (70%) responded by March 31, 1996. The data presented here are from 132 facilities. One hundred seventeen facilities (89%) answered that they were connected to the Internet. More than 80% of them got access to the Internet in the past two years. One hundred three facilities (78%) answered that e-mail was available. Despite the large percentage being connected, only 11 facilities (8%) had their own homepages. However, just 6 months later more than 25 facilities could be found by their own homepages. The Global Health Network (GHNet) has been developed in the USA based upon the concept that the best means to produce improved health is a better surveillance and information system applying the latest telecommunication technology to public health. The GHNet will offer an initial homepage for Preventive and Environmental Medicine related facilities in Japan to promote and establish sustainable connectivity among them.
PMCID: PMC2723330  PMID: 21432450
Telecommunication; Internet; Connectivity; Homepage; Network

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