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BackgroundRecently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change.ObjectiveTo examine secular trends in patients' anthropometric indices.SubjectsJapanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes.MethodsWe 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 ResultsData 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.ConclusionsSince 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.

BACKGROUND: The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet. METHODS AND RESULTS: By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. A large NICCD cohort of 116 Chinese cases was also established, and the 4 high-frequency mutations contributed a much larger proportion of the mutated alleles in the patients from south China than in those from the north (χ(2) = 14.93, P

In the Japanese education system, school year for various grade levels begins on the 1st April. Depending on the starting month of the school year and the birth—month of children, height may vary among children in the same grade level with an age difference of up to 12 months. We examined the associations between birth—month and outpatient clinic visits for short—stature. A total of 2,389 children with a height standard deviation score（SDS）of ≤－2.0 were stratified according to sex and further divided into four groups according to their birth—month：January—March, April—June, July—September, and October—December. We then sought to examine hypothesis testing that population proportions are 25％ in each group. Comparisons of height SDS showed no statistical difference among the groups in each sex. Among boys, 30.1％ were born in January—March, and among girls, 32.2％ were born in January—March, with statistically significant differences in both sexes（p＜0.001）. In the group aged 6—11 years, the percentage was the highest in patients born in January— March and the lowest in patients born in April—June, with a significant difference in both sexes（p＜0.001）. Relative short—stature due to birth—month is likely to have contributed to the corresponding outpatient visits. Children born in April—June may avoid visiting the clinic due to the relative age effect. Encouraging such children to visit clinics may be more helpful in diagnosing treatable diseases. [ABSTRACT FROM AUTHOR]

SHOX resides in the short arm pseudoautosomal region (PAR1) of the sex chromosomes and escapes X inactivation. SHOX haploinsufficiency underlies idiopathic short stature (ISS) and Leri-Weill dyschondrosteosis (LWD). A substantial percentage of cases with SHOX haploinsufficiency arise from pseudoautosomal copy number variations (CNVs) involving putative enhancer regions of SHOX. Our previous study using peripheral blood samples showed that some CpG dinu- cleotides adjacent to SHOX exon 1 were hypomethylated in a healthy woman and methylated in a woman with gross X chromosomal rearrangements. However, it remains unknown whether submicroscopic pseudoautosomal CNVs cause aberrant DNA methylation of SHOX -flanking CpG islands. In this study, we examined the DNA methylation status of SHOX -flanking CpG islands in 50 healthy individuals and 10 ISS/LWD patients with pseudoautosomal CNVs. In silico analysis detected 3 CpG islands within the 20-kb region from the translation start site of SHOX. Pyrosequencing and bisulfite sequencing of genomic DNA samples revealed that these CpG islands were barely methylated in peripheral blood cells and cultured chondrocytes of healthy individuals, as well as in peripheral blood cells of ISS/LWD patients with pseudoautosomal CNVs. These results, in conjunction with our previous findings, indicate that the DNA methylation status of SHOX -flanking CpG islands can be affected by gross X-chromosomal abnormalities, but not by submicroscopic CNVs in PAR1. Such CNVs likely disturb SHOX expression through DNA methylation-independent mechanisms, which need to be determined in future studies. [ABSTRACT FROM AUTHOR]

Congenital hyperinsulinism is a rare condition and following recent advances in diagnosis and treatment, it was considered necessary to formulate evidence-based clinical practice guidelines reflecting the most recent progress, to guide the practice of neonatologists, pediatric endocrinologists, general pediatricians and pediatric surgeons. These guidelines cover a range of aspects, including general features of congenital hyperinsulinism, diagnostic criteria and tools for diagnosis, first-and second-line medical treatment, criteria for and details of surgical treatment, and future perspectives. These guidelines were generated as a collaborative effort between The Japanese Society for Pediatric Endocrinology and The Japanese Society of Pediatric Surgeons and followed the official procedures of guideline generation to identify important clinical questions, perform a systematic literature review (April 2016), assess the evidence level of each paper, formulate the guidelines and obtain public comments. [ABSTRACT FROM AUTHOR]