Effect of the COVID-19 pandemic lockdown on the physique of school-age children in Japan.

PURPOSE: Schools in Japan were closed nationwide from March to May 2020 because of the coronavirus disease 2019 (COVID-19) pandemic. Many suspect that this school closure affected children's mental and physical health. We investigated changes in school-age children's physiques to determine the effects of the COVID-19 lockdown and restrictions on their health. METHODS: Data were extracted from a database of school physical examinations in Osaka elementary and junior high schools for 4 consecutive years from 2018 to 2021. The following characteristics were analyzed: short stature, tall stature, underweight, mild obesity, middle grade obesity, and severe obesity. The paired Student t-test was used to compare school examination data in the prepandemic period (2018-2019), pandemic lockdown (2019-2020), and post-lockdown period (2020-2021). RESULTS: Obesity rates in elementary school students aged 6-12 years, particularly in boys, were significantly higher during the lockdown than they were in 2019. After the pandemic, the tall stature rate continued to rise, while rates of short stature and underweight decreased in both sexes in 2020. In junior high school students aged 12-15 years, rates of obesity and underweight tended to decrease in 2020. However, these rates rebounded and rose in 2021 when the lockdown was lifted. CONCLUSION: During the COVID-19 pandemic lockdown, elementary school students gained weight, while junior high school students lost weight. The lockdown that was implemented during the COVID-19 pandemic had an unfavorable effect on weight gain, particularly in young school-age children.

Impact of childhood growth and obesity curves in school health examinations.

BACKGROUND: With the revision of the Japanese School Health and Safety Law in 2016, the use of growth and obesity curves has been recommended. This study aimed to determine the prevalence of growth and obesity curve creation in elementary and junior high schools using government-issued software in Japan between 2016 and 2019. METHODS: A questionnaire survey was conducted with school nursing teachers in elementary and junior high schools in Osaka, Japan. The questionnaire was distributed and collected by e-mail between 1 and 31 March 2020. RESULTS: The survey response rate was 87.1%. In total, 78.5% of the elementary schools, and 75.0% of the junior high schools had the software for creating the growth curves. The rate of adoption of growth curve creation using the software increased in elementary schools (from 16.2% in 2016 to 40.5% in 2019 and in junior high schools from 6.0% in 2016 to 33.6% in 2019. The detection rates of growth abnormalities also increased over the 4 years in elementary and junior high schools, as follows: short stature (2.48- and 3.81-fold, respectively), tall stature (2.77- and 4.77-fold, respectively), emaciation (2.62 and 4.85-fold, respectively), mild obesity (2.66 and 5.15-fold, respectively), moderate obesity (2.71- and 4.14-fold, respectively), and severe obesity (2.45- and 3.32-fold, respectively). The rates of receiving a recommendation slip and going on to consult a specialist for each growth abnormality were low. CONCLUSIONS: By utilizing these curves, the detection rate of physical development abnormalities increased, but the rate of recommending a specialist consultation and the rate of actual consultation with a specialist were still low.

Regional disparities in obesity/emaciation and income in schoolchildren in Osaka City.

BACKGROUND: We assessed the association between socioeconomic status at residential area-level in the 24 wards of Osaka City, differentiated by indices of mean income-related deprivation, and inequalities in childhood obesity and emaciation. METHODS: Data from representative samples of 26 474 schoolchildren (first and fifth grades of elementary school, and third grade of junior high school [i.e. ninth grade of elementary school]) in Osaka City taken from a somatometric check in spring 2016 were analyzed. The cross-sectional association between socioeconomic factors, that is, the census-based annual income of each ward, and the prevalence of childhood overweight/obesity and emaciation, was examined. RESULTS: The prevalence of overweight/obesity in boys and girls in the first and fifth grades of elementary school and the third grade of junior high school was 3.98% and 4.53%, 10.18% and 8.69%, and 7.02% and 5.55%, respectively. The prevalence of emaciation in boys and girls in the first and fifth grades of elementary school, and the third grade of junior high school was 0.14% and 0.10%, 0.46% and 1.06% and 3.95% and 3.05%, respectively. Mean physical value, expressed as % degree of overweight, had a negative correlation with mean annual income of each ward in girls in the first and fifth grades of elementary school, girls in the third grade of junior high school and boys in the first grade of elementary school. CONCLUSIONS: Overweight/obesity at school age is greatly affected by poverty. Efforts should be made to prevent emaciation not only in girls, but also in boys, in junior high school.

Microvascular endothelial function in Japanese early adolescents.

Endothelial dysfunction is the early predictive factor for the development of atherosclerosis and future cardiovascular diseases in adulthood. The prevalence of endothelial dysfunction in children and early adolescents is increasing worldwide. Peripheral arterial tonometry is a noninvasive technique for assessing peripheral microvascular function and is used as a validated marker of endothelial function. We assessed anthropometric parameters, blood pressure, arterial stiffness, and peripheral endothelial function in 157 Japanese early adolescents (75 boys and 82 girls). We measured peripheral endothelial function by using peripheral arterial tonometry to determine the reactive hyperemia index, and assessed the association of reactive hyperemia index with parameters of anthropometry and arterial stiffness. The mean reactive hyperemia index of all subjects was 1.85 ± 0.6, and there was no difference of reactive hyperemia index according to sex. Reactive hyperemia index was significantly associated with systolic and diastolic blood pressures, and had no correlation with anthropometric parameters and arterial stiffness markers. The reactive hyperemia index values among Japanese early adolescents were similar to those reported in previous studies on children and early adolescents. This noninvasive technique may be useful for the assessment of microvascular endothelial function among children and early adolescents.

Evaluation of uric acid levels, thyroid function, and anthropometric parameters in Japanese children with Down syndrome.

Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.

Development of waist circumference percentiles for Japanese children and an examination of their screening utility for childhood metabolic syndrome: a population-based cross-sectional study.

BACKGROUND: In Japan, waist circumference (WC) percentiles to screen for childhood metabolic syndrome (MetS) are unavailable. The objectives of this study were to develop WC and WC-to-height ratio (WC/Ht) percentile curves by age and sex for Japanese children, and to test their utility in screening for MetS in children with obesity who are otherwise healthy. METHODS: The WC and WC/Ht percentiles were developed using the LMS method of summarizing growth standards, which monitors changing skewness (L), medians (M), and coefficients of variation (S) in childhood distributions. A representative dataset was used, which consisted of 3,634 boys and 3,536 girls aged 4.5-12.75 years in Shizuoka prefecture, Japan, between 2010 and 2012. Children who were obese (355 boys and 230 girls) aged 6-12 years from Osaka prefecture, Japan, were screened for childhood MetS using the new percentiles and the International Diabetes Federation's (IDF's) definition of MetS. RESULTS: The number of participants with certain metabolic abnormalities (high systolic and diastolic blood pressure, and a high level of triglycerides) was significantly higher in boys aged 10-12 years, with a WC ≥ 90th percentile, than among those with a WC < 90th percentile. None of the participants with a WC < 90th percentile exhibited two or more metabolic abnormalities, regardless of their age or sex. Among the participants aged 10-12 years, 11.4 % of boys and 4.4 % of girls with a WC ≥ 90th percentile were diagnosed with MetS. CONCLUSIONS: The new percentiles may have a certain level of potential to screen Japanese children for childhood MetS in accordance with the IDF definition.

Association of thyroid hormones with obesity and metabolic syndrome in Japanese children.

Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters.

Association of uric acid with obesity and endothelial dysfunction in children and early adolescents.

BACKGROUND: Hyperuricemia in adults is known to be associated with hypertension, the metabolic syndrome and cardiovascular disease. The purpose of this study was to elucidate the factors associated with hyperuricemia in obese children and early adolescents and to investigate the threshold serum level of uric acid (UA) for the metabolic syndrome in children. METHODS: We assessed anthropometric measurements, blood pressure, body composition and biochemical data in 1,559 obese children. To assess endothelial dysfunction, flow-mediated dilatation (FMD) was measured in 92 children. The correlations between serum UA levels and various parameters were examined. The threshold serum UA level for the metabolic syndrome was calculated by receiver-operating characteristic (ROC) curve analysis. RESULTS: Serum UA levels were positively correlated with lipids in both boys and girls, and they were inversely correlated with FMD in the boys but not the girls. The threshold serum UA level for the metabolic syndrome was 5.25 mg/dl in boys and 5.05 mg/dl in girls. However, the specificity and sensitivity of ROC curve analysis are not so striking. CONCLUSION: The correlation between UA and FMD showed gender differences and might be affected by the hormonal status. The cutoff level of serum UA as a marker of the metabolic syndrome in obese children was affected by both age and gender.

α-Tocopherol status and expression of α-tocopherol transfer protein in type 2 diabetic Goto-Kakizaki rats.

Vitamin E, a critical fat-soluble vitamin antioxidant, is expressed on cell membranes and prevents propagation of lipid peroxidation. α-Tocopherol transfer protein (α-TTP) is a cytosolic protein located in the hepatocytes that acts as the principal regulator of the circulating α-tocopherol levels. Type 2 diabetes is a metabolic disorder characterized by hyperglycemia, caused by insulin resistance. Lipid peroxidation promotes the clinical progression and development of complications in type 2 diabetes. Results of animal and human experiments on the vitamin E status in diabetes are conflicting. The present study was conducted with the objective of investigating the vitamin E status and α-TTP expression in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. In diabetic GK rats, increases of the α-tocopherol levels in the plasma and liver were observed as compared with the levels in the controls. No alternation in the CuZn-superoxide dismutase (SOD) or Mn-SOD gene expression was found in the liver of GK rats as compared with that in the controls. The GK rats showed an increase of the hepatic expression of the α-TTP gene as compared with the level in the controls. It can be suggested that the increased hepatic α-TTP gene expression levels may influence plasma α-tocopherol levels in the diabetic animals. Hence, investigation of the regulatory factors of α-TTP expression may provide important clues to highlighting the antioxidant mechanisms of vitamin E.

Identification of INS and KCNJ11 gene mutations in type 1B diabetes in Japanese children with onset of diabetes before 5 years of age.

BACKGROUND: The etiology of type 1 diabetes (T1D) is heterogeneous and is according to presence or absence of pancreatic autoantibodies divided into two subtypes: type 1A (autoimmune-mediated) and type 1B (non-autoimmune-mediated). Although several genes have been linked to type 1A diabetes, the genetic cause of type 1B diabetes in Japanese individuals is far from understood. OBJECTIVE: The aim of this study was to test for monogenic forms of diabetes in auto antibody-negative Japanese children with T1D. METHODS: Thirty four (19 males and 15 female) unrelated Japanese children with glutamate decarboxylase (GAD) 65 antibodies and/or IA-2A-negative T1D and diabetes diagnosed at < 5 yr of age were recruited from 17 unrelated hospitals participating in the Japanese Study Group of Insulin Therapy for children and adolescent diabetes (JSGIT). We screened the INS gene and the KCNJ11 gene which encode the ATP-sensitive potassium cannel by direct sequencing in 34 Japanese children with T1D. RESULTS: We identified three novel (C31Y, C96R, and C109F) mutations and one previously reported mutation (R89C) in the INS gene in five children, in addition to one mutation in the KCNJ11 gene (H46R) in one child. These mutations are most likely pathogenic and therefore the cause of diabetes in carriers. CONCLUSION: Our results suggest that monogenic forms of diabetes, particularly INS gene mutations, can be detected in Japanese patients classified with type 1B. Mutation screening, at least of the INS gene, is recommended for Japanese patients diagnosed as autoantibody negative at <5 yr of age.

Delayed onset congenital hypothyroidism in a patient with DUOX2 mutations and maternal iodine excess.

Congenital hypothyroidism (CH), one of the most common congenital endocrine disorders, causes irreversible intellectual disability in untreated patients. Today, the vast majority of patients receive early diagnosis and treatment in the context of newborn screening for CH, and achieve satisfactory cognitive development. However, a subset of patients with delayed onset are undetectable by newborn screening, and miss benefit from early intervention. Here, we report on a delayed-onset CH patient that had two contributing factors in the pathogenesis of CH simultaneously, i.e., a genetic defect and iodine excess. The patient was exposed to excessive iodine in utero because her mother consumed massive amounts of seaweed during pregnancy. Surprisingly, the patient had a negative result in newborn screening, but developed overt CH at age 3 months. She received thyroxine supplementation until when normalization of the thyroid function was confirmed at age 3 years (i.e., transient CH). Mutation screening for DUOX2, a causative gene for transient CH, showed biallelic mutations (p.[E327X] + [H678R]). This report provides a new example of environmental modification of phenotypes of CH due to a genetic defect, which can potentially distort screening results.

HLA-class II and class I genotypes among Japanese children with Type 1A diabetes and their families.

OBJECTIVE: To determine the HLA-DRB1, DQB1, DPB1, A, C, and B genotypes among Japanese children with autoimmune type 1 diabetes. METHODS: Four hundred and thirty patients who were GADAb and/or IA-2Ab-positive (Type 1A) were recruited from 37 medical centers as part of a nationwide multicenter collaborative study. DNA samples from 83 siblings of the children with Type 1A diabetes and 149 parent-child trios were also analyzed. A case-control study and a transmission disequilibrium test (TDT) were then performed. RESULTS: The susceptible and protective DRB1 and DQB1 alleles and haplotypes were confirmed. DPB1 alleles unique to the Japanese population and those common to multiple ethnic groups were also present. A linkage disequilibrium (LD) analysis showed both susceptible and protective haplotypes. The TDT did not reveal any alleles that were transmitted preferentially from the mother or father to children with Type 1A. Homozygosity for DRB1-09:01-DQB1-03:03 and heterozygosity for DRB1-04:05-DQB1-04:01 and DRB1-08:02-DQB1-03:02 were associated with an extremely high risk of Type 1A. A comparison of children with Type 1A and their parents and siblings suggested a dose effect of susceptible DRB1-DQB1 haplotypes and an effect of protective alleles on immunological pathogenesis. DRB1-09:01 appeared to be strongly associated with an early onset in preschool children with Type 1A diabetes. CONCLUSIONS: This study demonstrated the characteristic association of HLA-class II and class I genes with Type 1A diabetes among Japanese children. A TDT did not reveal the genomic imprinting of HLA-class II and class I genes in Type 1A diabetes.

Altered expression of both ß-carotene 15,15' monooxygenase and lecithin:retinol acyltransferase in obese Zucker rats.

Retinol and its active derivative retinoic acid have an important role in development, reproduction, immunity, and cell proliferation/differentiation. Obesity and dyslipidemia are risk factors for cardiovascular disease that may affect hepatic homeostasis. It is unclear whether the expression of retinol-related proteins is affected and influences the retinol status in obesity and dyslipidemia. The aim of this study was to evaluate the retinol status and expression of retinol-metabolizing enzymes and binding protein in obese and dyslipidemic fa/fa (Zucker) rats. We examined the expression of genes for ß-carotene 15,15' monooxygenase (BCM), lecithin:retinol acyltransferase (LRAT), cellular retinol binding protein-I (CRBP-I), and cytochrome P450 26A1 (CYP26A1) in fa/fa rats and lean control rats. We also measured the retinol level in plasma and liver samples from both groups. Plasma retinol levels in fa/fa rats were increased compared with lean rats, while hepatic retinol levels were similar in both groups. In obese and dyslipidemic fa/fa rats, intestinal BCM gene expression was increased, whereas hepatic LRAT gene expression was deceased. There was no difference in hepatic CRBP-I and CYP26A1 gene expression between fa/fa rats and lean rats. Altered expression of BCM and LRAT genes may affect plasma retinol status in obesity and dyslipidemia.

Quantitative study on cerebral blood volume determined by a near-infrared spectroscopy during postural change in children.

AIM: To investigate changes in cerebral blood volume during standing in healthy children with or without abnormal cardiovascular responses. METHODS: We studied 53 children (age, 10-15 years). Cerebral oxygenated haemoglobin (oxy-Hb) and deoxygenated Hb (deoxy-Hb) were non-invasively and continuously measured using near-infrared spectroscopy (NIRS) (NIRO 300, Hamamatsu Photomedics, Shizuoka, Japan) during active standing. Beat-to-beat arterial pressure was monitored by Portapres. RESULTS: Of 49 children with complete data acquisition, 33 had a normal cardiovascular response to the test (Group I) and 16 showed an abnormal response (Group II); nine with instantaneous orthostatic hypotension, three with postural tachycardia syndrome, three with neutrally mediated syncope and one with delayed orthostatic hypotension. At the onset of standing, Group II showed a significantly larger fall of oxy-Hb than Group I did (-2.9 +/- 2.8 micromol/L vs. -6.4 +/- 7.2 micromol/L, respectively, p < 0.05). During min 1 to 7 of standing, with one exception, changes in oxy-Hb were normally distributed over the level of -4 micromol/L in Group I. Group II also showed a significantly marked decrease in oxy-Hb compared to Group I. Decreases in oxy-Hb were not correlated with blood pressure changes. CONCLUSION: This study shows that precise change in cerebral blood volume caused by orthostatic stress can be determined by NIRS in children in a quantitative manner of NIRS. Children with abnormal circulatory responses to standing showed a significant reduction of oxy-Hb compared with normal counterparts, suggesting impairment of cerebral autoregulation in these children.

Expression of beta-carotene 15,15'-monooxygenase gene and retinol status in type 2 diabetic Goto-Kakizaki rats.

The vitamin A status has been studied in type 2 diabetes and it is known that plasma retinol levels of patients with type 2 diabetes are elevated. However, the details of vitamin A metabolism in type 2 diabetes are unclear. beta-Carotene exhibits biological activity as provitamin A and beta-carotene 15,15'-monooxygenase (BCM) cleaves beta-carotene to form retinal. We studied BCM gene expression in type 2 diabetic Goto-Kakizaki (GK) rats. BCM gene expression was analyzed in the liver, intestine, and testis of 8- and 13-week-old GK rats and Wistar rats (control). The plasma and liver retinol levels were measured, and plasma retinol-binding protein (RBP) was detected. BCM gene expression in the liver, intestine and testis of GK rats was increased compared with that in controls. Plasma retinol levels and RBP levels were increased in GK rats, but hepatic retinol levels did not differ between GK rats and controls. BCM gene expression in the liver and intestine might affect retinol levels in type 2 diabetes. Conversion of beta-carotene to retinal might be accelerated in the presence of insulin resistance status, so that plasma retinol levels are increased in type 2 diabetes.

Criteria for medical intervention in obese children: a new definition of 'obesity disease' in Japanese children.

The Committee of the Japan Society for the Study of Obesity reported the new criteria for 'obesity disease' for Japanese adults in 2000. We defined the criteria for the diagnosis of obesity in children with medical problems, corresponding to the 'obesity disease' criteria in adults. Obesity in childhood was defined as follows: percentage of overweight (POW) and body fat exceeded the criteria. 'Obesity disease in childhood' was defined as obesity associated with health or medical problems, and with indications for medical intervention. Medical problems with indications for immediate intervention were grouped as A problems, which consisted of (i). hypertension; (ii). sleep apnea or hypoventilation; (iii). Type 2 diabetes mellitus or impaired glucose tolerance; and (iv). increased waist circumference or accumulation of visceral adipose tissue. Metabolic derangements or equivalent associated with obesity were grouped as B problems: (i). liver dysfunction; (ii). hyperinsulinemia; (iii). hypercholesterolemia; (iv). hypertriglyceridemia; (v). low serum high-density lipoprotein cholesterol; (vi). acanthosis nigricans, and (vii). hyperuricemia. Obese children over 5 years of age with following conditions were diagnosed as 'obesity disease in childhood': (i). any 'A problem', (ii) POW >or= 50% and any 'B problem', or (3) POW < 50% and more than one 'B problem' or equivalent. We decided to take physicosocial problems related to obesity into consideration as the criteria. The resultant criteria are proposed by the Committee for Research of Appropriate Body Build in Children*.

Efficacy of high sodium intake in a boy with instantaneous orthostatic hypotension.

We report the case of a 14-year-old boy with instantaneous orthostatic hypotension (INOH) with symptoms of orthostatic intolerance. We investigated the effect of high sodium intake on hemodynamics and circulatory responses to orthostatic stress using Portapres. Moreover, a multifrequency bioelectrical impedance method was used to confirm increased plasma volume. Although we began treatment with an alpha-adrenoceptor agonist after his admission into our hospital, the effect was not sufficient. We, therefore, began a regimen of high sodium intake (NaCl 3 g two times a day per os in addition to regular diet, NaCl 5-6 g /day) to increase plasma volume. As a result, 48 hours after sodium intake, orthostatic tolerance was markedly improved with a concomitant increase in blood pressure in the orthostatic test. By measuring the patient's body water before and after the high sodium intake, we were able to document the increase in plasma volume. We conclude that high sodium intake is an effective treatment for orthostatic hypotension in combination with vasoactive drugs.

Nutritional status of beta-carotene, alpha-tocopherol and retinol in obese children.

We investigated the concentrations of beta-carotene, alpha-tocopherol, and retinol in obese children, together with assessment of the influence of relative body weight and plasma lipids. A lower plasma beta-carotene level was observed in the obese children, and plasma beta-carotene was inversely correlated with the relative body weight, but not with plasma total lipids. In contrast, the plasma alpha-tocopherol concentration was correlated with plasma total lipids, but not with the severity of obesity. Both the beta-carotene/plasma total lipids ratio and the alpha-tocopherol/plasma total lipids ratio were decreased in hyperlipidemic children, while there was a slight increase of the plasma retinol concentration. There was a marked elevation of the plasma beta-carotene concentration and a reduction of the alpha-tocopherol concentration corresponding to the changes of plasma lipids with diet and exercise. We conclude that different kinetics of the fat-soluble vitamins such as beta-carotene and alpha-tocopherol exists during dieting and exercise in obese children.