Third Report of the Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer: Summary of the results of a questionnaire survey of oncologists and diabetologists-Secondary publication.

The Japan Diabetes Society and the Japan Cancer Association launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and health-care providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology and the Japanese Society of Medical Oncology, reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey indicated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients.

Efficacy and safety of once-weekly insulin icodec versus once-daily basal insulin in Japanese individuals with type 2 diabetes: A subgroup analysis of the ONWARDS 1, 2 and 4 trials.

AIM: To explore the efficacy and safety of once-weekly insulin icodec (icodec) in Japanese adults (≥20 years old) with type 2 diabetes from the global ONWARDS 1, 2 and 4 trials. MATERIALS AND METHODS: Insulin-naive (ONWARDS 1) and insulin-experienced (ONWARDS 2 and 4) individuals were randomized to icodec or a once-daily insulin comparator: insulin glargine U100 [ONWARDS 1 (basal insulin only) and 4 (basal-bolus regimen)] or insulin degludec [ONWARDS 2 (basal insulin only)]. The primary outcome was change in glycated haemoglobin from baseline to end of treatment (EOT) (ONWARDS 1: Week 52; ONWARDS 2 and 4: Week 26). Here, we present the Japanese subgroup results. RESULTS: Similar reductions in glycated haemoglobin from baseline to EOT were observed in each trial for icodec and comparators. The proportion of time in range (blood glucose 3.9-10.0 mmol/L) at EOT was also comparable across treatment groups (time in range: 58%-68%), as was time spent with blood glucose below 3.0 mmol/L (<1.0%). Combined clinically significant (blood glucose <3.0 mmol/L) or severe (requiring external assistance for recovery) hypoglycaemia rates were low, with no severe events (ONWARDS 1 and 2) or a single severe event (ONWARDS 4; icodec group) reported. These results generally aligned with findings from the respective global populations. No new safety issues were identified. CONCLUSIONS: Icodec improved glycaemic control to a similar degree as once-daily basal insulin comparators while maintaining low levels of clinically significant or severe hypoglycaemia. The findings support icodec use in Japanese individuals with different levels of type 2 diabetes progression.

Guidelines for clinical evaluation of chronic kidney disease in early stages : AMED research on regulatory science of pharmaceuticals and medical devices.

BACKGROUND: For the development of pharmaceutical products in kidney field, appropriate surrogate endpoints which can predict long-term prognosis are needed as an alternative to hard endpoints, such as end-stage kidney disease. Though international workshop has proposed estimated glomerular filtration rate (GFR) slope reduction of 0.5-1.0 mL/min/1.73 m /year and 30% decrease in albuminuria/proteinuria as surrogate endpoints in early and advanced chronic kidney disease (CKD), it was not clear whether these are applicable to Japanese patients. METHODS: We analyzed J-CKD-DB and CKD-JAC, Japanese databases/cohorts of CKD patients, and J-DREAMS, a Japanese database of patients with diabetes mellitus to investigate the applicability of eGFR slope and albuminuria/proteinuria to the Japanese population. Systematic review on those endpoints was also conducted including the results of clinical trials published after the above proposal. RESULTS: Our analysis showed an association between eGFR slope and the risk of end-stage kidney disease. A 30% decrease in albuminuria/proteinuria over 2 years corresponded to a 20% decrease in the risk of end-stage kidney disease patients with baseline UACR ≥ 30 mg/gCre or UPCR ≥ 0.15 g/gCre in the analysis of CKD-JAC, though this analysis was not performed on the other database/cohort. Those results suggested similar trends to those of the systematic review. CONCLUSION: The results suggested that eGFR slope and decreased albuminuria/proteinuria may be used as a surrogate endpoint in clinical trials for early CKD (including diabetic kidney disease) in Japanese population, though its validity and cutoff values must be carefully considered based on the latest evidence and other factors.

Rho-kinase inhibitor restores glomerular fatty acid metabolism in diabetic kidney disease.

The small GTPase Rho and its effector Rho-kinase (ROCK) are activated in the diabetic kidney, and recent studies decade have demonstrated that ROCK signaling is an integral pathway in the progression of diabetic kidney disease. We previously identified the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism in diabetic glomeruli. However, the effect of pharmacological intervention for ROCK1 is not clear. In the present study, we show that the inhibition of ROCK1 by Y-27632 and fasudil restores fatty acid oxidation in the glomeruli. Mechanistically, these compounds optimize fatty acid utilization and redox balance in mesangial cells via AMPK phosphorylation and the subsequent induction of PGC-1α. A further in vivo study showed that the inhibition of ROCK1 suppressed the downregulation of the fatty acid oxidation-related gene expression in glomeruli and mitochondrial fragmentation in the mesangial cells of db/db mice. These observations indicate that ROCK1 could be a promising therapeutic target for diabetic kidney disease through a mechanism that improves glomerular fatty acid metabolism.

Rho-associated, coiled-coil-containing protein kinase 1 regulates development of diabetic kidney disease via modulation of fatty acid metabolism.

Dysregulation of fatty acid utilization is increasingly recognized as a significant component of diabetic kidney disease. Rho-associated, coiled-coil-containing protein kinase (ROCK) is activated in the diabetic kidney, and studies over the past decade have illuminated ROCK signaling as an essential pathway in diabetic kidney disease. Here, we confirmed the distinct role of ROCK1, an isoform of ROCK, in fatty acid metabolism using glomerular mesangial cells and ROCK1 knockout mice. Mesangial cells with ROCK1 deletion were protected from mitochondrial dysfunction and redox imbalance driven by transforming growth factor ß, a cytokine upregulated in diabetic glomeruli. We found that high-fat diet-induced obese ROCK1 knockout mice exhibited reduced albuminuria and histological abnormalities along with the recovery of impaired fatty acid utilization and mitochondrial fragmentation. Mechanistically, we found that ROCK1 regulates the induction of critical mediators in fatty acid metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1α, carnitine palmitoyltransferase 1, and widespread program-associated cellular metabolism. Thus, our findings highlight ROCK1 as an important regulator of energy homeostasis in mesangial cells in the overall pathogenesis of diabetic kidney disease.

Effects of individualized dietary advice compared with conventional dietary advice for adults with type 2 diabetes: A randomized controlled trial.

BACKGROUND AND AIMS: To investigate the superiority of individualized dietary advice based on dietary assessment for patients with type 2 diabetes. METHODS AND RESULTS: A total of 136 Japanese adults with type 2 diabetes were randomized into either individualized or conventional dietary advice groups after dietary assessment using a self-administered brief-type diet history questionnaire. Both participants received three 30-min face-to-face dietary advice sessions by dietitians at 1, 3, and 5 months from study entry. The individualized group received dietary advice based on individual dietary intakes. The conventional group received dietary advice using generalized pamphlets. The primary outcome was the change in HbA1c over 6 months, and secondary outcomes were changes in weight, serum triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and dietary intakes. In total, 126 participants were included in the analysis. After adjustment for age, sex, and baseline measurements, HbA1c significantly decreased larger in the individualized group [-1.1%, (95% CI: -1.3 to -0.8)] than the conventional group [-0.7% (95% CI: -1.0 to -0.4)] (P = 0.0495). The individualized group significantly decreased weight, serum triglyceride, and LDL-C, and significantly increased HDL-C, without a significant difference to the conventional group. In dietary changes, the individualized group decreased intakes of energy, confectioneries, meats, oil and fats, and sugar-sweetened beverages. The conventional group decreased alcohol intake and increased total fat and saturated fatty acid intakes. CONCLUSIONS: Individualized dietary advice among patients with type 2 diabetes was superior to conventional dietary advice in lowering HbA1c. TRIAL REGISTRATION: UMIN000037268 (https://www.umin.ac.jp/ctr/index.htm) in July 4, 2019.

Eicosapentaenoic acid/arachidonic acid ratio in Japanese junior high school students.

BACKGROUND: This epidemiological study investigated the eicosapentaenoic acid/arachidonic acid ratio (EAR) and docosahexaenoic acid/ arachidonic acid ratio (DAR) in ninth-graders in Japan. METHODS: A total of 175 ninth-grade children from Tsunan Town (115 boys and 60 girls) were enrolled in the study between 2015 and 2017. All participants were assessed during annual health checkups to determine their EAR and DAR. All data were compared between boys and girls using the Mann-Whitney test. Spearman's rank correlation coefficient was used to describe the strengths of correlations between the EAR, DAR, and relevant parameters. RESULTS: The median (minimum, maximum) EAR and DAR of all participants were 0.13 (0.05, 0.46) and 0.47 (0.25, 0.84), respectively. There was no significant difference in the EAR between boys and girls at 0.12 (0.05, 0.46) and 0.13 (0.06, 0.27) (P = 0.375), respectively. The DAR was not significantly different (P = 0.125). There was a significant positive correlation between EAR and triglyceride, body mass index, and homeostasis model assessment but a significantly negative correlation with HbA1c (r = -0.209, P = 0.006). In contrast, there was no significant correlation between DAR and any parameters. CONCLUSIONS: This is the first epidemiological study investigating the EAR using a population-based cohort of Japanese adolescents. The EAR in boys/girls in Japan is 0.12 (0.05, 0.46)/0.13 (0.06, 0.27). The study results suggest that children with a healthy diet may generally have a lower average blood glucose level.

Protein Kinase C (Pkc)-δ Mediates Arginine-Induced Glucagon Secretion in Pancreatic α-Cells.

The pathophysiology of type 2 diabetes involves insulin and glucagon. Protein kinase C (Pkc)-δ, a serine-threonine kinase, is ubiquitously expressed and involved in regulating cell death and proliferation. However, the role of Pkcδ in regulating glucagon secretion in pancreatic α-cells remains unclear. Therefore, this study aimed to elucidate the physiological role of Pkcδ in glucagon secretion from pancreatic α-cells. Glucagon secretions were investigated in Pkcδ-knockdown InR1G9 cells and pancreatic α-cell-specific Pkcδ-knockout (αPkcδKO) mice. Knockdown of Pkcδ in the glucagon-secreting cell line InR1G9 cells reduced glucagon secretion. The basic amino acid arginine enhances glucagon secretion via voltage-dependent calcium channels (VDCC). Furthermore, we showed that arginine increased Pkcδ phosphorylation at Thr505, which is critical for Pkcδ activation. Interestingly, the knockdown of Pkcδ in InR1G9 cells reduced arginine-induced glucagon secretion. Moreover, arginine-induced glucagon secretions were decreased in αPkcδKO mice and islets from αPkcδKO mice. Pkcδ is essential for arginine-induced glucagon secretion in pancreatic α-cells. Therefore, this study may contribute to the elucidation of the molecular mechanism of amino acid-induced glucagon secretion and the development of novel antidiabetic drugs targeting Pkcδ and glucagon.

Eating Fast and Until Full Is Associated with Elevated Alanine Aminotransferase Activity in Japanese Schoolchildren: A Cross-Sectional Study.

Alanine aminotransferase (ALT) activity has been recognized as a marker for monitoring the risk of metabolic syndrome, diabetes and non-alcoholic fatty liver disease in children. Higher ALT activity was reported to be associated with eating fast in Japanese adults, but the association in children is unclear. Moreover, eating fast and eating until full are reported to be associated with being overweight. This study examined the association between elevated ALT and eating behaviors (eating fast and eating until full) among population-based schoolchildren (aged 9-10 years) in Ina Town, Saitama, Japan. Data for eating behaviors were obtained from a self-written questionnaire. Blood samples were drawn to measure ALT. Elevated ALT was defined as > 30 U/L in boys and > 19 U/L in girls. Logistic regression models and structural equation models were used to calculate the effect of eating behaviors on elevated ALT. Final data analysis was carried out for 1,870 boys and 1,739 girls. "Eating fast and eating until full" was significantly associated with elevated ALT in each sex. "Eating fast and not eating until full" was significantly associated with elevated ALT in boys, but after adjusting for exercise and body mass index, this association was not significant. In conclusion, "eating fast and eating until full" was associated with elevated ALT in schoolchildren. A sex difference in the association of "eating fast and not eating until full" with elevated ALT was observed. Modifying the behaviors of eating fast and eating until full is important for schoolchildren to prevent ALT elevation.

Glycolaldehyde induces sensory neuron death through activation of the c-Jun N-terminal kinase and p-38 MAP kinase pathways.

Glycolaldehyde (GA) is a highly reactive hydroxyaldehyde and one of the glycolytic metabolites producing advanced glycation endproducts (AGEs), but its toxicity toward neurons and Schwann cells remains unclear. In the present study, we found that GA exhibited more potent toxicity than other AGE precursors (glyceraldehyde, glyoxal, methylglyoxal and 3-deoxyglucosone) against immortalized IFRS1 adult rat Schwann cells and ND7/23 neuroblastoma × neonatal rat dorsal root ganglion (DRG) neuron hybrid cells. GA affected adult rat DRG neurons and ND7/23 cells more severely than GA-derived AGEs, and exhibited concentration- and time-dependent toxicity toward ND7/23 cells (10 < 100 < 250 < 500 µM; 6 h < 24 h). Treatment with 500 µM GA significantly up-regulated the phosphorylation of c-jun N-terminal kinase (JNK) and p-38 mitogen-activated kinase (p-38 MAPK) in ND7/23 cells. Furthermore, GA-induced ND7/23 cell death was significantly inhibited due to co-treatment with 10 µM of the JNK inhibitor SP600125 or the p-38 MAPK inhibitor SB239063. These findings suggest the involvement of JNK and p-38 MAPK-signaling pathways in GA-induced neuronal cell death and that enhanced GA production under diabetic conditions might be involved in the pathogenesis of diabetic neuropathy.

Changes in overweight/obesity and central obesity status from preadolescence to adolescence: a longitudinal study among schoolchildren in Japan.

BACKGROUND: Little is known about changes in overweight/obesity and central obesity status among schoolchildren from preadolescence to adolescence in Japan, where waist circumference (WC) is generally not measured in annual health examinations at elementary and junior high schools. This study examined changes of overweight/obesity and central obesity status among schoolboys and schoolgirls from preadolescence to adolescence in Japan. METHODS: Study subjects were fourth-grade school children (9 or 10 years of age) from all four of Ina town's elementary schools in Japan. Measurement of each participant's height, weight, and WC were made at baseline and 3 years later. Childhood overweight/obesity was determined according to the age- and sex-specific body mass index cut-off points proposed by the International Obesity Task Force. Central obesity was defined as waist-to-height ratio ≥ 0.5. Kappa (κ) statistic was calculated to examine the tracking of overweight/obesity and central obesity. RESULTS: Data from 1436 participants (boys: n = 720, girls: n = 716) were analyzed. Overweight/obesity status tracked substantially from fourth grade to seventh grade in both boys (κ = 0.614, P value < 0.001) and girls (κ = 0.619, P value < 0.001). Among participants who were overweight/obese in fourth grade, 55.2% of boys and 63.2% of girls were still overweight/obese in seventh grade. Tracking of central obesity from fourth graders to seventh graders was substantial in boys (κ = 0.651, P value < 0.001) and moderate in girls (κ = 0.544, P value < 0.001). Among participants who had central obesity in fourth grade, 54.1% of boys and 52.6% of girls still had central obesity in seventh grade. CONCLUSIONS: The present study showed that the tracking of overweight/obesity from preadolescence to adolescence was substantial in boys and girls. Moreover, more than half of those who had central obesity in preadolescence had central obesity in adolescence. This study suggests that it is important to implement a primary prevention program for overweight/obesity and central obesity in elementary schools before fourth grade.

ROCK2 regulates TGF-ß-induced expression of CTGF and profibrotic genes via NF-κB and cytoskeleton dynamics in mesangial cells.

The small GTPase Rho and its effector Rho kinase (ROCK) are involved in the pathogenesis of diabetic kidney disease. Rho kinase has two isoforms: ROCK1 and ROCK2. However, it remains unclear which is mainly involved in the progression of diabetic glomerulosclerosis and the regulation of profibrotic mediators. Glomeruli isolated from type 2 diabetic db/db mice demonstrated increased gene expression of transforming growth factor (TGF)-ß and its downstream profibrotic mediators. Chemical inhibition of ROCK suppressed the expression of profibrotic mediators in both isolated glomeruli and cultured mesangial cells. An investigation of mechanisms underlying this observation revealed activated ROCK functions through the phosphorylation of JNK and Erk and the nuclear translocation of NF-κB via actin dynamics. Knockdown by siRNA against ROCK1 and ROCK2 showed that ROCK2 but not ROCK1 controls this fibrotic machinery. Further in vivo experiments showed that ROCK2 activity in the renal cortex of db/db mice was elevated compared with control db/m mice. Importantly, oral administration of ROCK2 inhibitor attenuated renal ROCK2 activity, albuminuria, and glomerular fibrosis in db/db mice. These observations indicate that ROCK2 is a key player in the development of diabetic renal injury. Glomerular ROCK2 may be a potential therapeutic target for the treatment of diabetic kidney disease.

Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease.

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) and is therefore a major burden on the healthcare system. Patients with DKD are highly susceptible to developing cardiovascular disease, which contributes to increased morbidity and mortality rates. While progress has been made to inhibit the acceleration of DKD, current standards of care reduce but do not eliminate the risk of DKD. There is growing appreciation for the role of inflammation in modulating the process of DKD. The focus of this review is on providing an overview of the current status of knowledge regarding the pathologic roles of inflammation in the development of DKD. Finally, we summarize recent therapeutic advances to prevent DKD, with a focus on the anti-inflammatory effects of newly developed agents.

Relationship between Eating Quickly and Overweight : A Cohort Study of Schoolchildren in Japan.

Several cross-sectional studies have shown that eating quickly is associated with overweight in children and adolescents. However, few cohort studies have examined this relationship. Here we investigated the relationship between eating quickly and overweight in a cohort study of fourth-grade schoolchildren (aged 9 or 10 years) who attended elementary schools in Ina-town, Japan. The children were followed for 3 years from 2001-2004 (at baseline) to 2004-2007. A questionnaire survey including information about eating speed (fast, medium, or slow) was administered, and height and weight measurements were obtained at baseline and follow-up. Overweight was defined according to the body mass index cutoff points proposed by the International Obesity Task Force. We used a Poisson regression model to examine the association between eating quickly at baseline and being overweight 3 years later. Data from 934 non-overweight children (465 boys, 469 girls) were analyzed. Eating quickly was not significantly associated with being overweight in the boys, whereas it was significantly associated with being overweight in the girls. Our analysis indicates that among girls, eating quickly leads to overweight, and that the modification of eating quickly could help prevent overweight in adolescents.

Efficacy and safety of empagliflozin in patients with type 2 diabetes from Asian countries: pooled data from four phase III trials.

We investigated the efficacy and safety of empagliflozin over 24 weeks in Asian patients with type 2 diabetes (T2DM) using pooled data from four phase III trials. In these trials, patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo as monotherapy or add-on to metformin, metformin plus sulphonylurea or pioglitazone ± metformin. In total, 1326 patients from Asia received ≥1 dose of study drug. At week 24, adjusted mean differences versus placebo in change from baseline in glycated haemoglobin (HbA1c) were -0.66% [95% confidence interval (CI) -0.76, -0.56] and -0.73% (95% CI -0.83, -0.64) and in weight were -1.6 kg (95% CI -1.9, -1.3) and -1.8 kg (95% CI -2.1, -1.5) with empagliflozin 10 and 25 mg, respectively (all p < 0.001). Empagliflozin significantly reduced systolic and diastolic blood pressure. The proportion of patients reporting ≥1 adverse event was similar across treatment groups, but events consistent with genital infection were more common in patients treated with empagliflozin 10 mg (3.4%) or 25 mg (2.3%) than placebo (0.9%). Thus in Asian patients with T2DM, empagliflozin reduced HbA1c, weight and blood pressure, and was well tolerated.

Effect of empagliflozin monotherapy on postprandial glucose and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled, 4-week study.

BACKGROUND: This study evaluated the effect of empagliflozin on postprandial glucose (PPG) and 24-hour glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM). METHODS: Patients (N = 60; baseline mean [SD] HbA1c 7.91 [0.80]%; body mass index 24.3 [3.2] kg/m(2)) were randomized to receive empagliflozin 10 mg (n = 20), empagliflozin 25 mg (n = 19) or placebo (n = 21) once daily as monotherapy for 28 days. A meal tolerance test and continuous glucose monitoring (CGM) for 24 hours were performed at baseline and on days 1 and 28. The primary endpoint was change from baseline in area under the glucose concentration-time curve 3 hours after breakfast (AUC1-4h for PPG) at day 28. RESULTS: Adjusted mean (95%) differences versus placebo in changes from baseline in AUC1-4h for PPG at day 1 were -97.1 (-126.5, -67.8) mg · h/dl with empagliflozin 10 mg and -91.6 (-120.4, -62.8) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -85.5 (-126.0, -45.0) mg · h/dl with empagliflozin 10 mg and -104.9 (-144.8, -65.0) mg · h/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Adjusted mean (95% CI) differences versus placebo in change from baseline in 24-hour mean glucose (CGM) at day 1 were -20.8 (-27.0, -14.7) mg/dl with empagliflozin 10 mg and -23.9 (-30.0, -17.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo) and at day 28 were -24.5 (-35.4, -13.6) mg/dl with empagliflozin 10 mg and -31.7 (-42.5,-20.9) mg/dl with empagliflozin 25 mg (both p < 0.001 versus placebo). Changes from baseline in mean amplitude of glucose excursions (MAGE; CGM) were not significantly different with either empagliflozin dose versus placebo at either timepoint. Curves of mean glucose (CGM) did not change between baseline and day 1 or 28 with placebo, but shifted downward with empagliflozin. Percentage of time with glucose ≥70 to <180 mg/dl increased from 52.0% at baseline to 77.0% at day 28 with empagliflozin 10 mg and from 55.0% to 81.1% with empagliflozin 25 mg, without increasing time spent with hypoglycemia. CONCLUSION: Empagliflozin for 28 days reduced PPG from the first day and improved daily blood glucose control in Japanese patients with T2DM. TRIAL REGISTRATION: Clinicaltrials.gov NCT01947855.

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.

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.