Performance evaluation of case definitions of type 1 diabetes for health insurance claims data in Japan.

BACKGROUND: No case definition of Type 1 diabetes (T1D) for the claims data has been proposed in Japan yet. This study aimed to evaluate the performance of candidate case definitions for T1D using Electronic health care records (EHR) and claims data in a University Hospital in Japan. METHODS: The EHR and claims data for all the visiting patients in a University Hospital were used. As the candidate case definitions for claims data, we constructed 11 definitions by combinations of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision. (ICD 10) code of T1D, the claims code of insulin needles for T1D patients, basal insulin, and syringe pump for continuous subcutaneous insulin infusion (CSII). We constructed a predictive model for T1D patients using disease names, medical practices, and medications as explanatory variables. The predictive model was applied to patients of test group (validation data), and performances of candidate case definitions were evaluated. RESULTS: As a result of performance evaluation, the sensitivity of the confirmed disease name of T1D was 32.9 (95% CI: 28.4, 37.2), and positive predictive value (PPV) was 33.3 (95% CI: 38.0, 38.4). By using the case definition of both the confirmed diagnosis of T1D and either of the claims code of the two insulin treatment methods (i.e., syringe pump for CSII and insulin needles), PPV improved to 90.2 (95% CI: 85.2, 94.4). CONCLUSIONS: We have established a case definition with high PPV, and the case definition can be used for precisely detecting T1D patients from claims data in Japan.

Efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

AIM: To assess the efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, double-blind, parallel-group study randomized Japanese patients with T2D insufficiently controlled with insulin (1:1:1) to empagliflozin 10 mg (n=89), empagliflozin 25 mg (n=90) or placebo (n=90) for 52 weeks. The primary endpoint was change from baseline in glycated haemoglobin (HbA1c) at 16 weeks. RESULTS: At 16 weeks, empagliflozin 10 mg and 25 mg significantly decreased HbA1c: adjusted mean difference -0.92% (95% confidence interval [CI] -1.11, -0.73) and -1.00% (95% CI -1.18, -0.82; both P<0.0001) compared with placebo. This difference was maintained up to 52 weeks: adjusted mean difference at 52 weeks -0.90% (95% CI -1.09, -0.70) and -0.96% (95% CI -1.15, -0.77; both P<0.0001). At 52 weeks, significant improvements in fasting plasma glucose (adjusted mean difference -27.62 mg/dL [95% CI -36.15, -19.08] and -31.99 mg/dL [95% CI -40.35, -23.62]) and in body weight (-1.78 kg [95% CI -2.46, -1.10] and -1.92 kg [95% CI -2.58, -1.25]) were also seen with empagliflozin 10 mg and 25 mg compared with placebo (all P<0.0001). At 52 weeks, the frequency of adverse events (AEs) and serious AEs was similar in the three treatment groups; confirmed hypoglycaemia was reported slightly more in participants in the empagliflozin 10 mg and 25 mg groups (23.3% and 22.2% vs 14.4%). All hypoglycaemic events were mild in severity; no episodes required assistance. CONCLUSIONS: In Japanese patients with insufficiently controlled T2D, adding empagliflozin 10 mg or 25 mg to insulin treatment was associated with clinically meaningful reductions in HbA1c at 16 weeks and was generally well tolerated.

High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C ß Signaling.

Activation of mineralocorticoid receptor (MR) is shown in resistant hypertension including diabetes mellitus. Although protein kinase C (PKC) signaling is involved in the pathogenesis of diabetic complications, an association between PKC and MR is not known. Activation of PKCα and PKCß by TPA (12-O-Tetradecanoylphorbol 13-acetate) increased MR proteins and its transcriptional activities in HEK293-MR cells. In contrast, a high glucose condition resulted in PKCß but not PKCα activation, which is associated with elevation of MR protein levels and MR transcriptional activities. Reduction of endogenous PKCß by siRNA decreased those levels. Interestingly, high glucose did not affect MR mRNA levels, but rather decreased ubiquitination of MR proteins. In db/db mice kidneys, levels of phosphorylated PKCß2, MR and Sgk-1 proteins were elevated, and the administration of PKC inhibitor reversed these changes compared to db/+ mice. These data suggest that high glucose stimulates PKCß signaling, which leads to MR stabilization and its transcriptional activities.

Report of the Japan diabetes society/Japanese cancer association joint committee on diabetes and cancer, Second report.

The Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer published its first report in July 2013 on the epidemiological assessment of the associations of diabetes with cancer risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk associated with diabetes treatment. The Joint Committee continued its work to assess the role of glycemic control in the development of cancer in patients with diabetes. This review shows that high-quality evidence examining the association between glycemic control and cancer risk is lacking.

The estrogen receptor ß-PI3K/Akt pathway mediates the cytoprotective effects of tocotrienol in a cellular Parkinson's disease model.

Tocotrienols (T3s) are members of the vitamin E family, have antioxidant properties, and are promising candidates for neuroprotection in the pathogenesis of neurodegenerative disorders such as Parkinson's disease (PD). However, whether their antioxidant capacities are required for their cytoprotective activity remains unclear. In this regard, the antioxidant-independent cytoprotective activity of T3s has received considerable attention. Here, we investigated the signaling pathways that are induced during T3-dependent cytoprotection of human neuroblastoma SH-SY5Y cells, as these cells are used to model certain elements of PD. T3s were cytoprotective against 1-methyl-4-phenylpyridinium ion (MPP(+)) and other PD-related toxicities. γT3 and δT3 treatments led to marked activation of the PI3K/Akt signaling pathway. Furthermore, we identified estrogen receptor (ER) ß as an upstream mediator of PI3K/Akt signaling following γT3/δT3 stimulation. Highly purified γT3/δT3 bound to ERß directly in vitro, and knockdown of ERß in SH-SY5Y cells abrogated both γT3/δT3-dependent cytoprotection and Akt phosphorylation. Since membrane-bound ERß was important for the signal-related cytoprotective effects of γT3/δT3, we investigated receptor-mediated caveola formation as a candidate for the early events of signal transduction. Knockdown of caveolin-1 and/or caveolin-2 prevented the cytoprotective effects of γT3/δT3, but did not affect Akt phosphorylation. This finding suggests that T3s and, in particular, γT3/δT3, exhibit not only antioxidant effects but also a receptor signal-mediated protective action following ERß/PI3K/Akt signaling. Furthermore, receptor-mediated caveola formation is an important event during the early steps following T3 treatment.

Trends of Underweight and Overweight/Obesity Among Japanese Schoolchildren From 2003 to 2012, Defined by Body Mass Index and Percentage Overweight Cutoffs.

BACKGROUND: We investigated the prevalence and trends of underweight and overweight/obesity in a population-based sample of Japanese schoolchildren from 2003 to 2012, defined by body mass index (BMI) and percentage overweight (POW). METHODS: Subjects comprised fourth and seventh graders from the town of Ina, Japan, from 2003 to 2012. The height and weight of each subject were measured. Children were classified as underweight, normal weight, or overweight/obese using two criteria: BMI cutoff points proposed by the International Obesity Task Force and cutoffs based on POW in Japan. RESULTS: Data from 4367 fourth graders and 3724 seventh graders were analyzed. The prevalence of underweight and overweight as defined by POW criteria were lower than those based on BMI criteria. There was a decrease in the prevalence of overweight among fourth-grade boys and girls and seventh-grade girls according to BMI; this decrease was also observed when POW criteria were used for the definition of overweight. CONCLUSIONS: The prevalence and trends of both underweight and overweight as defined by POW were underestimated among Japanese schoolchildren compared to those determined using BMI. The results of this study also suggest that trends in underweight and overweight/obesity using POW criteria are similar to those based on BMI criteria among schoolchildren in Japan.

Waist-to-height ratio is more closely associated with alanine aminotransferase levels than body mass index and waist circumference among population-based children: a cross-sectional study in Japan.

BACKGROUND: An association between anthropometric measurements, including waist circumference (WC), and alanine aminotransferase (ALT) levels has been reported among adults. However, studies conducted among population-based elementary schoolchildren to date have been limited, especially in Japan, where the measurement of WC and blood collection are not usually performed in the annual health examination at elementary schools. The present study investigated the association between anthropometric measurements and ALT levels among population-based elementary schoolchildren in Japan. METHODS: Subjects were fourth-grade schoolchildren (aged 9 or 10) from the town of Ina in Saitama Prefecture, Japan during 2004-2009. The height, weight, and WC of each subject were measured, and blood samples were drawn to measure ALT levels. Childhood overweight or obesity was defined according to the age- and sex-specific cut-off points proposed by the International Obesity Task Force. Spearman's correlation coefficients between anthropometric measurements (body mass index (BMI), WC, and waist-to-height ratio (WHtR)) and ALT levels were calculated. RESULTS: Data from 2499 subjects (1293 boys and 1206 girls) were analyzed. BMI, WC, and WHtR were significantly positively correlated with ALT levels; the correlation coefficient of ALT levels with WHtR was higher than that with BMI and WC in boys and girls. In the analysis stratified by physique (non-overweight/obesity, overweight, or obesity), all anthropometric measurements were significantly positively correlated with ALT levels among boys, while only WHtR was significantly positively correlated with ALT levels among girls. Moreover, the correlation coefficient of ALT levels with WHtR was more pronounced than that with BMI and WC in the non-overweight/obesity group, in the overweight group, and in the obesity group for each sex. CONCLUSIONS: The present study showed that WHtR was more closely associated with ALT levels than BMI and WC. Furthermore, only WHtR was significantly positively associated with ALT levels regardless of sex and physique. This study suggests that it is more useful to monitor WHtR than BMI and WC as a surrogate for ALT levels among population-based elementary schoolchildren.

Sphingosine-1-phosphate induces differentiation of cultured renal tubular epithelial cells under Rho kinase activation via the S1P2 receptor.

BACKGROUND: Sphingosine-1-phosphate (S1P) is reportedly involved in the pathogenesis of kidney disease; however, the precise role played by S1P in renal disorders still remains controversial. Rho kinase plays an important role in the development of diabetic nephropathy by inducing glomerular and tubulointerstitial fibrosis. Rho kinase is known to be stimulated by S1P through its specific receptor, S1P2 receptor (S1P2). Hence, we investigated whether S1P-S1P2 signaling plays a role in the epithelial-mesenchymal transition (EMT) through Rho kinase activation in renal tubules. METHOD: To characterize the distribution of the S1P2, an immunohistochemical examination of the receptor was performed in the kidney of the non-diabetic and diabetic mice. Next, we examined Rho kinase activity as well as E-cadherin and alpha-smooth muscle actin (α-SMA) expression by real-time RT-PCR and western blotting in cultured rat tubular epithelial cells under S1P stimulation with and without a Rho kinase inhibitor and an S1P2 blocker. In addition, the distribution of E-cadherin and α-SMA was examined by immunocytochemistry. RESULT: S1P2 was expressed mainly in the renal tubules; expression was intense in collecting ducts and distal tubules compared to other segments. S1P induced activation of Rho kinase through the S1P2, which changed the distribution of E-cadherin and increased the expression of α-SMA. CONCLUSION: Rho kinase activation by S1P via S1P2 initiated EMT changes in cultured renal tubular cells. Our results suggest that excessive stimulation of S1P might facilitate renal fibrosis via activation of Rho kinase through S1P2.

The impact of eating quickly on anthropometric variables among schoolgirls: a prospective cohort study in Japan.

BACKGROUND: Because most studies about the relationship between eating quickly and overweight/obesity have been cross-sectional, it is necessary to investigate prospectively the influence of eating quickly on anthropometric variables in order to examine the causal relationship. The aim of the present study was to investigate the impact of eating quickly on anthropometric variables among schoolgirls in a prospective cohort study. METHODS: We investigated 427 non-overweight/obese schoolgirls from fourth grade (aged 9 or 10 years) in Ina-town, Japan from 2004 to 2006. Physical examinations and a questionnaire survey were conducted in fourth grade and 3 years later (in seventh grade). Height, weight, percent body fat (%BF) and waist circumference (WC) were measured in physical examinations, and information on eating speed was collected in a questionnaire survey. RESULTS: The differences in anthropometric variables (body mass index, %BF, WC and waist-to-height ratio) between fourth and seventh grade were significantly greater in girls who continued to eat quickly from fourth to seventh grade than in those who did not continue to eat quickly during this 3-year period. In contrast, these differences were not statistically significant in girls who ate quickly in fourth grade but not in seventh grade compared with those who did not continue to eat quickly during the 3-year period. CONCLUSION: Eating quickly was associated with excess gains in anthropometric variables. The present study also suggested that stopping a habit of eating quickly prevents these excess gains in non-overweight/obese girls, which could contribute to the prevention of childhood overweight and obesity.

Abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan: a cross-sectional study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention Prospective study (JDCP study 10).

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN.

Prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy in Japanese patients with type 2 diabetes: the Japan Diabetes Complication and its Prevention Prospective study (JDCP study 10).

Aim/introduction: This study aims to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective (JDCP) study. Materials and methods: In the study, 6338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using t test, chi-square test, and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Results: Of the total participants, 5451 patients (mean age 61.4 years old and duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased risk for DSPN: age [odds ratio (OR) 1.57, 95% confidence intervals (CI) 1.42-1.73], duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39), and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). Conclusions: The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also revealed the risk factors of DSPN.

Cause-specific mortality trends in a nationwide population-based cohort of childhood-onset type 1 diabetes in Japan during 35 years of follow-up: the DERI Mortality Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate long-term, cause-specific mortality trends among patients with childhood-onset type 1 diabetes in Japan. METHODS: Individuals included in the study had received a diagnosis of type 1 diabetes at age <18 years between 1965 and 1979. All individuals were followed up for their survival status until 1 January 2005. The causes of death were divided into end-stage renal disease (ESRD), acute diabetic complications (ADC), accident/suicide, cardiovascular disease (CVD), infections, cancers, others (non-diabetic/diabetic) and unknown. The cause-specific mortality trends were expressed according to the follow-up period and year of diagnosis. RESULTS: A total of 1,385 patients were enrolled in the study, and the survival status of 1,324 was confirmed. Mortality rate at the 35 year follow-up (per 100,000 person-years) was 659.3, and the standardised mortality ratio (SMR) was 10.7. The SMR at the 25 year follow-up markedly declined from 19.3 in the 1965-1969 diagnosis group to 6.6 in the 1975-1979 diagnosis group. Approximately 40% died of ADC among those with <10 years of follow-up. A similar proportion of individuals died of ESRD among those with 10-19 years of follow-up. The longer the duration of follow-up, the lower the mortality from ADC and the greater the mortality from CVD. CONCLUSIONS/INTERPRETATION: In Japanese people with childhood-onset type 1 diabetes of more than 20 years of duration, CVD was the leading cause of death, as is the case among similar white people. The longer the duration of diabetes, the more attention should be paid to preventing CVD.

Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer.

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk.

LDL-cholesterol and body mass index among Japanese schoolchildren: a population-based cross-sectional study.

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSION: A statistically significant association between LDL-C levels and BMI was observed in Japanese school children.

Causes of death in Japanese people with type 2 diabetes and factors associated with all-cause mortality from a large registry in Japan: the Japan Diabetes Complication and its prevention prospective (JDCP) study-9.

Aims: We aimed to estimate the causes of death and their incidence rates and risk factors for all-cause mortality in Japanese people with type 2 diabetes using baseline data from the Japan Diabetes Complication and its Prevention (JDCP) prospective study. Methods: We analyzed a multicenter prospective cohort of 5944 Japanese people with diabetes aged 40-74 years. Causes of death were categorized as cardiac or cerebrovascular disease, malignancy, infectious disease, accident or suicide, sudden death of unknown cause, and other unknown causes. The Cox proportional hazards model was used to estimate the hazard ratio of all-cause mortality risk factors. Results: The mean age was 61.4 years, and 39.9% of the population was female. Overall, the mortality ratio per 100,000 person-years (95% confidence interval [CI]) was 515.3 (95% CI 445.1-596.9). Malignancies are the most common cause of death among people with type 2 diabetes, accounting for 46.9% of all deaths, followed by cardiac and cerebrovascular diseases at 11.7% and infectious diseases at 3.9%. Higher mortality risk was significantly associated with older age, lower body-mass index, alcohol intake, history of hypertension, and acute myocardial infarction (AMI). Conclusions: The frequency of causes of death in people with type 2 diabetes identified in this study was similar to that from a recent survey on causes of death conducted by the Japan Diabetes Society. A lower body-mass index, alcohol intake, history of hypertension, and AMI were found to be associated with an increased total risk of type 2 diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00628-y.

Association of adipocytokines and adipocytokine ratios with cardiovascular risk factors in Japanese preadolescents.

OBJECTIVES: Asians are particularly susceptible to obesity-associated disorders and rapid progression of obesity from childhood to adulthood. Data on the association between adipocytokine parameters, particularly adipocytokine ratios, and cardiovascular risk factors in childhood remain limited. Herein, we assessed the association of resistin, adiponectin, and leptin levels and leptin/adiponectin and resistin/adiponectin ratios with selected cardiovascular risk factors and the influence of unhealthy weight on such associations in children aged 9-10 years. METHODS: We included 380 children aged 9-10 years from three public elementary schools in Japan. RESULTS: The body mass index (BMI) was significantly higher in male preadolescents than in female adolescents (median 16.5 kg/m2 vs. 16.2 kg/m2, p=0.032). No differences in height, weight, waist circumference (WC), waist/height ratio (W/Hr), total cholesterol and high-density lipoprotein cholesterol levels, or atherosclerosis index (AI) were observed between the sexes. Of the adipocytokine levels and ratios analyzed, only the leptin level and leptin/adiponectin ratio (L/Ar) were strongly and significantly positively correlated with the cardiovascular risk factors WC, W/Hr, and BMI (all p<0.05). The AI was not strongly correlated with any adipocytokine levels or ratios. Apart from the strong positive correlation between the L/Ar and W/Hr, no other significant associations were observed between any of the adipocytokine levels or ratios and the selected cardiovascular risk factors. CONCLUSIONS: Our findings confirmed the value of adipocytokine ratios in risk assessment in pediatric populations, with leptin levels and leptin/adiponectin ratios strongly correlating with risk factors in children aged 9-10 years.

Secular trends in blood pressure among Japanese schoolchildren: a population-based annual survey from 1994 to 2010.

BACKGROUND: Monitoring secular trends in blood pressure (BP) among children is important in predicting subsequent hypertension and cardiovascular disease. We investigated secular trends in BP using data from population-based annual screenings of Japanese schoolchildren. METHODS: The participants were 10 894 children (all fourth graders between 1994 and 2010 and all seventh graders between 1997 and 2010) living in the town of Ina in Saitama Prefecture, Japan. Body height, weight, and BP were measured, after which children were classified as non-overweight, overweight, or obese. Trends in variables relative to calendar year were analyzed using regression models. RESULTS: Systolic BP was significantly associated with calendar year among fourth- and seventh-grade boys (-0.350 and -0.434 mm Hg/year, respectively) and fourth- and seventh-grade girls (-0.513 and -0.473 mm Hg/year, respectively) (all P < 0.001), respectively, over time. Systolic BP and calendar year were significantly negatively correlated regardless of physique or sex among all fourth graders, but not among obese seventh-grade girls. In addition, diastolic BP and calendar year did not significantly correlate among seventh-grade overweight or obese boys or obese seventh-grade girls. CONCLUSIONS: BP decreased among fourth-grade schoolchildren in Ina during the past 17 years, regardless of sex or physique. However, BP and calendar year did not significantly correlate among obese seventh graders.

Number of siblings, birth order, and childhood overweight: a population-based cross-sectional study in Japan.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

High-molecular-weight adiponectin and anthropometric variables among elementary schoolchildren: a population-based cross-sectional study in Japan.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.