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Aim: To describe the development of HbA1c and BMI over time in Danish children with type 1 diabetes; and to investigate the association between HbA1c and BMI including influence of age, gender, diabetes duration, severe hypoglycaemia and treatment method. Methods: We used the nationwide Danish Registry of Childhood and Adolescent Diabetes, DanDiabKids, including annual registrations of all children with diabetes treated at Danish hospitals. With linear mixed‐effects models and splines we analyzed the HbA1c and BMI development over time as well as the association between HbA1c and BMI including effects of gender, age, disease duration, hypoglycaemia and treatment method. BMI z‐scores were calculated for these analyses. Results: For the period from 2000 to 2018, 6097 children with type 1 diabetes were identified from the DanDiabKids database. The median (interquartile range) HbA1c level was 65 (57–74) mmol/mol (8.1%) and the median BMI z‐score was 0.85 in girls and 0.67 in boys. A non‐linear association was found between HbA1c and BMI z‐score, with the highest BMI z‐score observed for HbA1c values in the range of approximately 60–70 mmol/mol (7.6–6.8%). The association was modified by gender, age and diabetes duration. Severe hypoglycaemia and insulin pump treatment had a small positive impact on BMI z‐score. Conclusion: The association between HbA1c and BMI z‐score was non‐linear, with the highest BMI z‐score being observed for intermediate HbA1c levels; however, specific patterns depended on gender, age and diabetes duration. [ABSTRACT FROM AUTHOR]

Introduction: Children and adolescents with recent-onset type 1 diabetes (T1D) commonly maintain a certain level of insulin production during the remission phase, which can last months to years. Preserving β-cell function can reduce T1D complications and improve glycaemic control. Influenza vaccination has pleiotropic effects and administration of the vaccine during the early phases of T1D may offer β-cell protection. This study aims to assess the effect of influenza vaccination on preserving β-cell function in children and adolescents with recent-onset T1D., Methods and Analysis: The INfluenza VaccInation To mitigate typE 1 Diabetes trial is a randomised, double-blind, placebo-controlled, multicentre trial in paediatric patients with recent-onset T1D aged 7-17 years. 100 participants will be randomised in a 1:1 ratio to receive either a standard inactivated quadrivalent influenza vaccine or a placebo within 14 days of diagnosis. The primary outcome is a difference in mean change (from baseline to 12 months) in C-peptide level between groups during a 2-hour mixed-meal tolerance test. Secondary outcomes include mean change (from baseline to 6 months) in C-peptide levels, haemoglobin A1c, ambulatory glucose profiles and insulin requirements. Exploratory outcomes are diabetes-related autoantibodies, inflammatory markers and serum haemagglutinin inhibition antibody titres against the influenza viruses. The current treatment for T1D is largely symptomatic, relying on insulin administration. There is a pressing need for novel pharmacological approaches aimed at modulating the immune system to preserve residual β-cell function. Existing immunotherapies are cost-prohibitive and associated with multiple side effects, whereas influenza vaccination is inexpensive and generally well tolerated. A positive outcome of this study holds potential for immediate implementation into standard care for children and adolescents with recent-onset T1D and may guide future research on immune modulation in T1D., Ethics and Dissemination: Ethical approval was obtained from Danish Health Authorities prior to participant enrollment. The trial results will be submitted to a peer-reviewed journal., Trial Registration Number: ClinicalTrials.gov NCT05585983 and EudraCT Number 2022-500906-17-01., Competing Interests: Competing interests: OF received study grants from Sanofi Pasteur and consultancy fees from GSK. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Childhood obesity is associated with impaired Quality-of-Life (QoL), increased stigmatization and higher risk of development of depression compared to their peers. This report describes the long-term development in QoL for cohort of children with obesity after a sustainable weight reduction., Methods: This pragmatic descriptive intervention study enrolled 120 children with obesity, age 5-17 years, in a multifactorial lifestyle intervention. The intervention was an across sectors collaboration between a department of pediatrics and community health care workers. QoL was assessed yearly throughout the intervention and evaluated by a 6-item Visual Analogue Scale (VAS). For analyzing changes in VAS, as function BMI-SDS, regression models were used, while ANOVA and Wilcoxon test were applied for normal and not-normal distributed data. 95% confidence interval not containing 0 and p-value < 0.05 was considered statistically significant., Results: After 26.4 months (13.9 SD) an overall decrease in bullying (0.6 vs. 0.0 median) and motivation (10.0 vs. 9.6) was observed. QoL increased in children with a BMI-SDS reduction (0.65 (2.49 SD)) opposite children with no-change or increasing BMI-SDS who reported reduced QoL (-0.36 (1.55 SD) and -0.96 (2.27 SD)). A significant inverse relationship was observed for Joy of Life, QoL and body perception as a function of BMI-SDS per year., Conclusion: Weight reduction causes improvement in QoL for children with obesity and an inverse relationship for QoL and changing BMI-SDS / year was establish., (© 2022. The Author(s).)

Introduction: Childhood obesity is an increasing condition associated with continuous obesity into adulthood and development of comorbidities. Adult studies show an association between serum uric acid (SUA) levels and body mass index (BMI). The aim of this retro perspective exploratory study was to investigate SUA in obese children and adolescents and the effects of a subsequent weight reduction. Materials and Methods: One hundred and seventy-one children (age 4-18), with obesity (i.e. BMI-SDS of +2 or higher) were included in a multifactorial lifestyle intervention. The children participating were annually measured for anthropometrics, blood samples and DEXA-scans for up to 3 years. Eighty-nine children were included for follow-up analysis. Results: After a follow-up of 20.7 ± 9.4 months a reduction in BMI-SDS of -0.34 ± 0.53 ( p < 0.01) was observed. SUA was found to be positively associated with changes in BMI-SDS. SUA levels decreased in the 65 children who lost weight during the trial, conversely, SUA increased in the 23 children who gained weight during the trial ( p < 0.01 between groups). Conclusion: SUA was found to correlate with measures of obesity and for the first time, this intervention demonstrates a positive relationship between SUA and weight reduction in children with obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jørgensen, Bøttger, Vestergaard, Kremke, Bahnsen, Nielsen and Bruun.)

Introduction: Childhood obesity has psychological consequences and increases the risk of continuous obesity into adulthood, associated with development of non-communicable disease (e.g. type 2 diabetes). Short-term weight loss intervention studies show good results but long-term studies are limited., Methods: One hundred ninety-nine obese children (4-18 years of age), with a BMI-SDS (standard deviation score) above + 2 SDS were enrolled into a multifactorial family-centered lifestyle intervention study. The children had yearly visits in the outpatient clinic for anthropometrics, blood samples and DXA-scans, and 6-8 meeting with community health workers between these visits. The children followed the intervention up to 3 years., Results: After a follow-up of 26.7 ± 17.5 months a reduction in BMI-SDS of - 0.25 SDS (p < 0.001) was observed. The 57 children who were adherent to the intervention for ≥ 2 years had significantly reduced BMI-SDS compared to the 142 children with shorter intervention (BMI-SDS: - 0.38 ± 0.67 vs. - 0.20 ± 0.50, p = 0.036). All weight loss was accompanied by decrease in fat mass and increase in muscle mass (p < 0.001)., Conclusion: The intervention was found to induce long-term reduction in BMI-SDS in obese children, with beneficial change in body composition. Children who followed the intervention the longest had the greatest reduction in BMI-SDS., Level of Evidence: Level III, longitudinal cohort study.

The GAD65 and IA-2 antibodies (Abs) are biomarkers of the development of type 1 diabetes mellitus (T1DM) in both children and adults. The upper reference limit for the autoantibodies made by the manufacture was established on an adult Chinese population. Here, we established upper reference limits for Northern European adults and children in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Serum samples from healthy Danish children (0-18 years) and adults (18-70 years) were analysed for GAD65Ab and IA-2Ab using MAGLUMI 800 Chemiluminescence Immunoassay (CLIA). The Kruskal-Wallis test was used for evaluating differences between gender and age groups. No gender or age differences were found for neither GAD65Ab nor IA-2Ab, and a combined upper reference limit for both children and adults could be established. An upper reference limit of 5.1 IU/mL was defined for GAD65Ab and 11.5 U/mL for IA-2Ab. Our results showed a substantial discrepancy with the reference limits established by the manufacturer.

Objective: To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls., Design: A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA., Setting: Not applicable., Patient(s): A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS)., Intervention(s): One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated)., Main Outcome Measure(s): Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment., Result(s): Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries., Conclusion(s): GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown., Clinical Trial Registration Number: EudraCT 2005-001507-19., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Mutations in the KCNJ11 gene encoding the adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) subunit Kir6.2 are the most frequent cause of diabetes in infancy. Sulfonylurea (SU) treatment restores insulin secretion in patients with KCNJ11 mutations., Materials and Methods: We report a 9-year-old boy who presented at the age of three months with diabetic ketoacidosis. Results Sequencing of the KCNJ11 gene revealed an R201H mutation. Therefore, he was transferred from insulin to oral SU therapy. He required a high-threshold dose before insulin could be discontinued. After transition, a subsequent dose reduction was necessary to avoid hypoglycemia. Improved sustained metabolic control without complications was achieved on a low SU maintenance dose twice daily over 36 months., Conclusion: SU therapy is safe for patients with diabetes due to KCNJ11 mutations. The mechanism of a threshold dose and the twice-daily requirement needs further attention.

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by mutations in SLC34A3, the gene encoding the renal sodium-phosphate co-transporter NaPi-IIc. Despite increased urinary calcium excretion, HHRH is typically not associated with kidney stones prior to treatment. However, here we describe two sisters, who displayed nephrolithiasis or nephrocalcinosis upon presentation. The index patient, II-4, presented with short stature, bone pain, and knee X-rays suggestive of mild rickets at age 8.5 years. Laboratory evaluation showed hypophosphatemia, elevated 1,25(OH) (2) vitamin D levels, and hypercalciuria, later also developing vitamin D deficiency. Her sister, II-6, had a low normal serum phosphorous level, biochemically vitamin D deficiency and no evidence for osteomalacia, but had undergone left nephro-ureterectomy at age 17 because of ureteral stricture secondary to renal calculi. Nucleotide sequence analysis of DNA from II-4 and II-6 revealed a homozygous missense mutation c.586G>A (p.G196R) in SLC34A3/NaPi-IIc. Ultrasonographic examinations prior to treatment showed grade I nephrocalcinosis for II-4, while II-6 had grade I-II nephrocalcinosis in her remaining kidney. Four siblings and the mother were heterozygous carriers of the mutation, but showed no biochemical abnormalities. With oral phosphate supplements, hypophosphatemia and hypercalciuria improved in both homozygous individuals. Renal calcifications that are presumably due to increased urinary calcium excretion can be the presenting finding in homozygous carriers of G196R in SLC34A3/NaPi-IIc, and some or all laboratory features of HHRH may be masked by vitamin D deficiency.

Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because spermatogenesis is dependent on androgens, some males may have a minimal form of androgen insensitivity that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility of abnormalities in the androgen receptor (AR) gene in a large cohort of males suffering from infertility of unknown cause. We studied 180 males with variable impairment of spermatogenesis. In all patients, serum levels of testosterone and gonadotropins were analyzed to define an androgen sensitivity index (ASI). Single-strand conformation analysis and direct DNA sequencing of PCR-amplified blood leukocyte DNA were used to identify mutations within the whole coding region of the AR-gene. Endocrine and molecular investigations were compared with 53 normal males with proven fertility. In three infertile males, mutations in the AR were identified. Two unrelated males had the same variation within the first exon encoding for the transactivation domain of the receptor (Pro390Ser), whereas, in the third, a mutation in the hormone-binding region was characterized (Gln798Glu). All identified mutation carriers had a significantly elevated ASI. A proportion of males with idiopathic infertility carry relevant variations within the AR-gene. These males may be distinguished on the basis of hormone levels, calculating the ASI, although this index lacks specificity.