Increasing secular trends in height and obesity in children with type 1 diabetes: JSGIT cohort.

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

Comparative alignment of the homologous proteins.

<p>The homologous proteins include human citrin (Homo sapiens) and aralar, and the others from 9 different eukaryotic species, i.e. Chimpanzee, Dog, Mouse, Rat, Chicken, Xenopus Tropicalis (X.Tropicalis), Caenorhabditis elegans (C. elegans), Opossum and Cow, respectively. The closed brown boxes in this figure represented the EF-hand or TM helices in citrin protein, as clarified in the reference by Kobayashi et al, 1999.</p

Identification of the large transposal insertion IVS4ins6kb (GenBank accession number: KF425758).

<p>Seven SNPs within the introns 4 and 5 were analyzed, and all of them were heterozygous but rs67843496 (The schematic overhead), an SNP detected heterozygously when amplified by the primers set A () while homozygously with set B (). LA-PCR with the primers set C yielded an unexpected band of 7.5 kb inherited from the mother C0054M besides the expected 1439 bp product from the father C0054F (). Segmental sequencing of the 7.5 bp product revealed a 6057 bp insertion from 16p11.2 (The sequence in green) along with two repetitive sequences of 15 bp at both sides (Shaded boxes), as illustrated in . Underlined were the positions of the primers IVS5F and IVS5A4 (Set C) for LA-PCR.</p

Frequency and proportion of the mutated <i>SLC25A13</i> alleles in the large Chinese Pediatric cohort.

*<p>Among the 116 patients, there were 3 siblings from 3 families. Therefore, the cohort comprised 226 mutated <i>SLC25A13</i> alleles in total, including 6 unknown ones.</p

Fifteen novel mutations in the <i>SLC25A13</i> gene of citrin-deficient patients from different countries.

<p>The bold black letters denote the novel mutations, “N” indicates the normal SLC25A13 allele, while “–” means not analyzed. The effects and frequency refer to the corresponding novel mutations. The frequency was calculated based on the screening result by PCR-RFLP (<b>^△</b>) or direct DNA sequencing approach (^▴), respectively.</p

PCR-RFLP approaches for the carrier rate investigation of the 5 novel missense mutations.

<p>The figures to were representative gel electrophoresis of the RE-digested PCR products of the mutations c.443A>G, c.527G>T, c.16-2A>T, c.1498T>G and c.1215G>T, while the figures to illustrated schematically the PCR-RFLP procedures for the 5 mutations, respectively. In , both the patient P917 and one of her brothers B1 harbored the maternally-inherited novel mutation c.16-2A>T.</p