Background Recently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change. Objective To examine secular trends in patients’ anthropometric indices. Subjects Japanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. Methods We analysed serum haemoglobin A1c (HbA1c) levels, the incidence of severe hypoglycaemic events, the types and doses of insulin, height standard deviation scores (SDS), body mass index (BMI) percentiles compared with healthy Japanese children and obesity prevalence over time. We also stratified the patients according to glycaemic control levels of <58 mmol/mol (optimal), 58–75 mmol/mol (suboptimal) and ≥75 mmol/mol (high-risk). Results Data for 513–978 patients from each of the cohorts were analysed. The incidence of severe hypoglycaemic events decreased over time (from 21 to 4.8/100 patient-years), while the proportion of insulin analogue doses increased (14.6% to 98.6%). In addition, patient height SDS (−0.22 to +0.17), BMI percentile (52.1 to 58.7) and obesity prevalence (2.1% to 5.1%) increased. Height SDS increased in all of the glycaemic control subgroups, while BMI percentile and obesity prevalence increased in the suboptimal and high-risk groups. Conclusions Since 1995, the average height of children with T1DM has increased in parallel with increasing insulin doses. Clinicians should be aware of increased BMI in these patients and the associated risk of developing cardiovascular disease in the future.

The aim of this study was to clarify the incidences of and the risk factors for severe retinopathy requiring photocoagulation therapy and albuminuria in Japanese patients with childhood-onset type 1 diabetes mellitus. A total of 756 patients from a cohort study by the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes were included in the study. Patients were registered in 1995 or 2000, and HbA1cwas measured every 4 months and analyzed in central hospital for an average of 6 years. The presence of severe retinopathy requiring laser photocoagulation and the presence of albuminuria was checked for during the period 2010-2011. During a median of 18 (range: 15-21) years, 34 out of 756 patients underwent laser photocoagulation and 57 out of 605 patients developed albuminuria. A Cox proportional hazards model showed that the risk of severe retinopathy requiring laser photocoagulation increased by 1.15 (95% confidence interval [CI] 1.03-1.29, p = 0.012) with each increase of a year in the age at onset, by 4.03 (95% CI 1.20-13.5, p = 0.024) in females, and by 2.05 (95% CI 1.69-2.49, p < 0.0001) with each increase of 1% in HbA1c. The risk of albuminuria increased significantly, by 1.09 (95% CI 1.01-1.18 p = 0.037), with each increase of a year in the age at onset and by 2.38 (95% CI 1.93-2.97 p < 0.0001) with each increase of 1% in HbA1c. In Japanese patients with childhood-onset type 1 diabetes, older age at the onset of diabetes, female rather than male gender, and higher HbA1c were found to increase the risk of requiring photocoagulation. No patients with HbA1c < 7.5% developed severe retinopathy requiring photocoagulation therapy. The risk of developing albuminuria increased with age at onset of diabetes and HbA1c. Female gender was a strong risk factor for severe retinopathy requiring photocoagulation, but not for albuminuria.

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes mellitus characterized by a remarkably abrupt onset. In Japan, FT1DM accounts for approximately 20% of acute-onset adult type 1 diabetes mellitus cases; however, reports of pediatric-onset FT1DM are rare. We aimed to determine the frequency and clinical characteristics of FT1DM in Japanese children and adolescents by conducting a 2-phase questionnaire survey among the members of the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) regarding their clinical experience with FT1DM. Responses were obtained from 54 of the 79 participating hospitals (68.4%). Of these, 8 hospitals managed a total of 15 pediatric patients with FT1DM (4 patients in each of 2 hospitals, 2 patients in 1 hospital, and 1 patient in each of 5 hospitals). The distribution of patient age was biphasic, with peaks in children younger than 5 years and older than 8 years of age. The clinical characteristics of FT1DM in this population (such as the duration from onset of symptoms to diagnosis, severity of symptoms, preceding flu-like episodes, and abnormal laboratory data) did not differ from those of patients with adult-onset FT1DM. The frequency of pediatric-onset FT1DM is low compared with that of adult-onset FT1DM. The genetic background and susceptibility patterns of pediatric patients with FT1DM may differ from those typical of adults with FT1DM, but both age groups share similar clinical characteristics.

Objective: Although insulin analogs have dramatically changed diabetes treatment, scarce evidence is available on those effects. We aimed to explore whether glycemic control had improved, the use of insulin analogs had been increased, and hypoglycemic events had decreased over time in Japanese pediatric patients with type 1 diabetes (T1D).Methods: Glycated hemoglobin A1c (HbA1c) values, proportion of insulin regimens, incidence of severe hypoglycemic events, and pubertal increase in HbA1c were compared in three cohorts of childhood-onset Japanese T1D patients (567 subjects in the 1995 cohort, 754 subjects in the 2000 cohort, and 806 subjects in the 2008 cohort).Results: Mean HbA1c values tended to decrease [78.5 mmol/mol (9.33%) in the 1995 cohort, 68.2 mmol/mol (8.39%) in the 2000 cohort, and 61.2 mmol/mol (7.75%) in the 2008 cohort; P < .0001]. The proportion of patients who received basal-bolus treatment tended to increase with statistical significance, as did the proportion on insulin analogs. The incidence of severe hypoglycemic events (events/100 patients/y) had decreased (19.1 in the 2000 cohort and 8.7 in the 2008 cohort; P = .02). The pubertal increase in HbA1c tended to decrease [males, 12.0 mmol/mol (1.10%) in 1995, 9.4 mmol/mol (0.85%) in 2008, and 9.4 mmol/mol (0.86%) in 2008; P = .55; females, 14.0 mmol/mol (1.28%) in 1995, 10.3 mmol/mol (0.94%) in 2000, and 4.2 mmol/mol (0.38%) in 2008; P = .0003].Conclusions: Glycemic control and incidence of severe hypoglycemic events were chronologically improved, especially in female adolescents.

Background: A nationwide, multicenter and observational study was retrospectively conducted to evaluate the clinical utility of Cepharanthin (CEP) for pediatric patients with chronic immune thrombocytopenia (ITP).Methods: Clinical and laboratory data for 46 Japanese patients aged <16 years who were diagnosed as having chronic ITP in 14 hospitals during 2001-2011, and were treated with CEP for >12 months, were analyzed.Results: Median daily CEP dose was 1 mg/kg (range, 0.12-2 mg/kg). Median platelet count prior to CEP was 20.5 x 10(9)/L (IQR, 8.3-53.0 x 10(9)/L), and then significantly increased to 58.5 x 10(9)/L (IQR, 22.8-115.0 x 10(9)/L) and 69.0 x 10(9)/L (IQR, 23.0-134.0 x 10(9)/L) at 12 and 24 months of treatment, respectively. No life-threatening bleeds or moderate-severe adverse events were reported. Of 38 patients who received both corticosteroids (CS) and CEP, 17 patients (45%) were weaned from CS, and 15 patients (39%) attained the reduced dose of CS. The duration from the start of CEP to the stopping of CS was a median of 413 days ( range, 49-1734 days) in patients who were weaned from CS.Conclusions: CEP alone or combined with CS was useful for the management of pediatric chronic ITPs.

Background: A nationwide, multicenter and observational study was retrospectively conducted to evaluate the clinical utility of cepharanthin (CEP) therapy for pediatric patients with chronic immune thrombocytopenia (ITP). A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. Methods: Clinical and laboratory data of 46 Japanese patients less than 16 years of age were analyzed, who were diagnosed as having chronic ITP in 14 hospitals during the 2001-2011 decade, and were treated with CEP for more than 12 months. Results: The median daily dose of CEP was 1 mg/kg (0.12–2). The platelet counts prior to CEP therapy were 20.5 ×10 9 /L (IQR 8.3-53.0), and were then significantly increased to 58.5 ×10 9 /L (IQR 22.8-115.0) and 69.0 ×10 9 /L (IQR 23.0-134.0) after 12 and 24 months of the treatment course, respectively. No life-threatening bleedings or moderate to severe adverse events were reported. Of 38 patients who received both corticosteroids (CS) and CEP, 17 patients (45%) were weaned from CS, and 15 patients (39%) attained the reduced dose of CS. The period from the start of CEP therapy to the stop of CS was median 413 days (range 49–1734) in patients who were weaned from CS. Conclusions: CEP alone or combined therapy with CS was found to be useful for the management of pediatric patients with chronic ITP.

Results The median values of HbA1c (% of glycemic goal <7.5%) were significantly improved between the subsequent three cohorts; 9.02% (18.6%), 8.10% (30.35) and 7.60% (44.1%), in 1st, 2nd and 3rd cohorts, respectively. In addition patients with HbA1c more than 9% were significantly decreased in that order of cohorts. The frequency of moderately severe hypoglycemia was 9 times/ 4 months/ 100 patients in 3rd cohort. The frequencies of multiple daily insulin or pump therapy were 34.5%, 59.7% and 80.7%, in that order. The daily insulin dose was higher in 3rd cohort in comparison with 1st cohort. While the height SD score significantly increased in 3rd cohort, the BMI SD scores in 2nd and 3rd cohorts were significantly higher than that in 1st cohort.

Objective: The aim of this study was to evaluate clinical manifestations, laboratory findings, and effects of antithyroid drugs in younger children with Graves' disease (GD).Design: A retrospective and collaborative study.Setting: Nine facilities in Chiba prefecture, Japan.Patients: We analyzed 132 children and adolescents with GD. The subjects were divided according to the median age into a group of young children (group I, 4.1-12.4 years, n=66) and an adolescent group (group II, 12.5-15.9 years, n=66).Main outcome measures: Clinical manifestations, laboratory findings, incidence of adverse effects, and remission rates 5 years after initial therapy were assessed.Results: The mean height SD score of group I (1.0) was higher than that of group II (0.3, p<0.001). The mean BMI SD score of group I (-0.7) was lower than that of group II (-0.3, p<0.05). The most common presentations were goiter, sweating, and hyperactivity in group I, whereas the most common presentations were goiter, sweating, and easy fatigability in group II. Hyperactivity was more frequent in group I (56.7%) than in group II (37.9%, p<0.05). Liver dysfunction appeared more often in group I (14.3%) than in group II (1.9%, p<0.05). There was no difference in the appearance of adverse effects between the two groups. The remission rate was slightly lower in group I (23.1%) than in group II (31.3%), but was not significant.Conclusions: Thyrotoxicosis had more influence on the growth and liver function in younger children.

Abstract Objective: Methimazole (MMI) is used as a first-line antithyroid drug in children and adolescents with Graves’ disease (GD). The aim of this study was to evaluate the correlation between the initial dose of MMI and the clinical course of GD after treatment. Design: Retrospective and collaborative study. Setting: Nine facilities in Chiba prefecture, Japan. Patients: Sixty-four children and adolescents with GD were analyzed. The subjects were divided into three groups by the initial daily dose of MMI: group A, 0.4±0.1 mg/kg (mean±SD, n=11); group B, 0.7±0.2 (n=37); group C, 0.9±0.2 (n=16). Main outcome measures: The duration of time required for normalization of serum free T4 on initial treatment and the incidence of adverse effects for 1 year after the start of MMI were compared. Outcomes were compared among patients who were followed more than 3 years (group A, n=7; group B, n=24; group C, n=12). Results: Mean duration of times for normalization of T4 was 1.9±1.5 months in group A, 1.6±0.9 in group B and 1.9±1.5 in group C (NS). No major adverse reactions were observed. Minor adverse effects occurred in 9.1% of cases in group A, 13.5% in group B and 62.0% in group C (p<0.01). Remission rates did not differ among the three groups. Conclusions: Higher doses of MMI are harmful for initial use in children and adolescents with GD.

A large number of children with type 2 diabetes mellitus (T2DM) and a small number with a slowly progressive form of type 1 diabetes mellitus (SPT1DM) have been detected by a urine glucose screening program conducted at Japanese schools since 1974. The incidence of T2DM in children has increased over the last 3 decades and is estimated to be approximately 3.0/100,000/year, which is twice as that of T1DM. In contrast, SPT1DM in children is more prevalent in Asians, particularly Japanese, and exhibits unique clinical features that differ from those of the rapid onset form of T1DM, usually seen in Caucasians. In the first part of this review, we summarize the urine glucose screening program conducted at Japanese schools and clinical characteristics of the 2 diabetic subtypes in Japanese children. In recent years, concerns regarding childhood diabetes in Asian countries, including Japan, have risen, and medical care for the same is exceedingly developing. Intensive insulin therapy such as basal-bolus therapy by multiple daily insulin injections and pump therapy, both using insulin analogs, has been increasing in pediatric patients with T1DM. In addition, various antidiabetic medications have been introduced for children with T2DM. In the second part of this review, we describe treatment of Japanese children with T1DM and T2DM and changes in glycemic control as a result of development of the treatment.

Objective: The aim of this study was to compare the efficacy and adverse reactions during initial treatment and long-term outcome between children and adolescents with Graves' disease (GD) treated with propylthiouracil (PTU) and those treated with methimazole (MMI).Design, setting and participants: Retrospective and collaborative study. Children and adolescents with GD were divided into group M (MMI: n = 64) and group P (PTU: n = 69) and into four subgroups by initial dose: group M1 (< 0.75 mg/kg of MMI, n = 34), group M2 (>= 0.75 mg/kg, n = 30), group P1 (< 7.5 mg/kg of PTU, n = 24) and group P2 (>= 7.5 mg/kg, n = 45).Main outcome measures: The duration for normalization of serum T4 on initial treatment, the incidence of adverse effects for one year and outcomes at 10 years after were compared.Results: Mean durations for normalization of T4 (+/- SD) were 1.7 +/- 1.0 months in group M and 2.3 +/- 2.4 in group P [not significant (NS)], while the mean duration in group P1 (3.1 +/- 3.3) was significantly longer than those in the other subgroups (M1: 1.9 +/- 1.2; M2: 1.4 +/- 0.7; P2; 1.7 +/- 1.3). No major adverse reaction was observed. Minor adverse effects occurred in 25.0% of cases in group M and 31.9% in group P (NS). The incidence in group P2 (44.4%) was significantly higher than those in group M1 (20.6%) and group P1 (8.3%). Remission rates did not differ between the MMI-treated group (35.0%, n = 20) and PTU-treated group (50.0%, n = 40).Conclusions: PTU may not be suitable for initial use in children and adolescents with GD, even with the risk of major adverse reactions such as liver failure excluded.

BACKGROUND:The aim of this study was to assess (i) the health-related quality of life (HR-QOL) of primary, junior and high school children with type 1 and type 2 diabetes and to compare it with that of healthy school children; and (ii) to compare the diabetes-related QOL (DR-QOL) and the QOL of parents of children with diabetes, between type 1 and type 2 diabetes in Japan. METHODS:Overall, 471 patients aged 9-18 years (368 with type 1 and 103 with type 2 diabetes) and their parents were involved. QOL was assessed using a self-administered questionnaire. RESULTS:The total score for HR-QOL of primary and junior school children with type 1 diabetes was significantly higher than that of those with type 2 diabetes and healthy controls. However, there were no significant differences in high school children. Some subscales regarding HR-QOL were significantly lower for children with type 2 diabetes than for children with type 1 diabetes or healthy controls. The DR-QOL of children with type 1 and type 2 diabetes did not significantly differ. The Family Burden and Family Involvement were significantly greater in parents of children with type 1 diabetes. There were significantly positive correlations between HR-QOL and DR-QOL in both groups. In type 1 diabetes only, there were significant negative correlations between glycated hemoglobin and some subscales of the HR-QOL and QOL of parents of children with diabetes, and weak positive correlation between glycated hemoglobin and Family Burden. CONCLUSIONS:The HR-QOL of school children with type 1 diabetes was higher than that of those with type 2 diabetes and healthy school children. The QOL of school children with type 1 diabetes was not impaired.

Background:Measles infection can be fatal in pediatric patients with chronic renal failure or in patients who have undergone renal transplantation, both of whom are in the immunosuppressed state. The efficacy of single, live measles vaccination in preventing infection was examined.Methods:Of 156 children with renal failure who underwent renal transplantation, the changes in antibody titer were investigated before and after renal transplantation in 125 children whose measles antibody titer could be examined, together with disease and vaccination histories. Live measles vaccine was administered to 42 children with negative antibody titer. The antibody seroconversion rate was then investigated in these children, along with rate of antibody maintenance and degree of antibody titer elevation.Results:Seroconversion rate was 97.6%. Antibody titers measured on HI and EIA were 72 +/- 118 fold (HI) and 36.9 +/- 31.3 (EIA), respectively. The geometric mean of the increase in antibody titer 6 months after vaccination was 15. No side-effects of vaccination were observed in any of the children.Conclusions:Live measles vaccination of children with chronic renal failure is effective and safe, because the seroconversion rate, rate of antibody titer maintenance and degree of antibody titer elevation in children with chronic renal failure were all equivalent to those of healthy children.

Pediatrics InternationalVolume 51, Issue 2 p. 300-302 Role of varicella virus and anticardiolipin antibodies in the development of stroke in a patient with Down syndrome associated with Moyamoya syndrome Masaaki Morino, Masaaki Morino Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this authorHideo Yamano, Hideo Yamano Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this authorNozomu Sasaki, Nozomu Sasaki Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this author Masaaki Morino, Masaaki Morino Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this authorHideo Yamano, Hideo Yamano Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this authorNozomu Sasaki, Nozomu Sasaki Department of Pediatrics, Saitama Medical School, Iruma-gun, Saitama, JapanSearch for more papers by this author First published: 30 March 2009 https://doi.org/10.1111/j.1442-200X.2009.02805.xCitations: 5 Masaaki Morino MD, Department of Pediatrics, Saitama Medical School, 38 Moroyama-mati, Iruma-gun, Saitama, 350-0495, Japan. Email: morino@saitama-med.ac.jp Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume51, Issue2April 2009Pages 300-302 RelatedInformation

The aim of the present study was to investigate health-related quality of life (HRQOL) and the living conditions of young adults with congenital hypothyroidism (CH) detected on newborn screening.Among medical institutions that care for CH patients in Japan and were approached to in the present study, 78 institutions agreed to participate. The World Health Organization Quality of Life-26 (WHO/QOL-26) was used for measurement of HRQOL. CH patients who gave consent after receiving an explanation from their physicians filled in questionnaires at home and sent them by mail. This survey involved 51 CH patients (15 male; 36 female) whose mean age was 21.1 +/- 2.7 years (+/- SD; range, 18-27 years). The data from WHO/QOL-26 forms completed by 43 patients (12 male; 31 female) were compared with those for healthy individuals.Mean WHO/QOL-26 scores were 3.51 +/- 0.43 for male patients and 3.59 +/- 0.42 for female patients, and there were no significant differences between them and healthy individuals (men, 3.32 +/- 0.42; women, 3.35 +/- 0.49). No significant difference was observed between patients and healthy individuals on any domain of the WHO/QOL-26. Their degree of educational attainment was not poor.The HRQOL of young adults with CH detected on newborn screening was not poor.

CONTEXTOrthodenticle homeobox 2 (OTX2) is a transcription factor necessary for ocular and forebrain development. In humans, heterozygous mutations of OTX2 cause severe ocular malformations. However, whether mutations of OTX2 cause pituitary structural abnormalities or combined pituitary hormone deficiency (CPHD) has not been clarified.OBJECTIVESWe surveyed the functional consequences of a novel OTX2 mutation that was detected in a patient with anophthalmia and CPHD.PATIENTWe examined a Japanese patient with growth disturbance, anophthalamia, and severe developmental delay. He showed deficiencies in GH, TSH, LH, FSH, and ACTH. Brain magnetic resonance imaging revealed a small anterior pituitary gland, invisible stalk, ectopic posterior lobe, and Chiari malformation.RESULTSSequence analysis of OTX2 demonstrated a heterozygous two bases insertion [S136fsX178 (c.576-577insCT)] in exon 3. The mutant Otx2 protein localized to the nucleus, but did not activate the promoter of the HESX1 and POU1F1 gene, indicating a loss of function mutation. No dominant negative effect in the presence of wild-type Otx2 was observed.CONCLUSIONThis case indicates that the OTX2 mutation is a cause of CPHD. Further study of more patients with OTX2 defects is necessary to clarify the clinical phenotypes and endocrine defects caused by OTX2 mutations.