Pediatric Endocrinology, Diabetes and Metabolism最新文献

Introduction: Type 1 diabetes mellitus (T1DM) is a common chronic childhood illness characterized by persistent hyperglycemia and glycosuria, caused by an insufficient amount of insulin due to the immune system attacking b cells in the pancreas. Autoantibodies against GAD65 are present in most individuals with T1DM. They can manifest years before the onset of the illness, acting as a prognostic indicator for the development of autoimmune diabetes. The study's objective was to evaluate glycated hemoglobin (HbA1c) levels and to determine the prevalence of glutamic acid decarboxylase 65 autoantibodies (anti-GAD65) in newly diagnosed Kurdish children with T1DM.

Material and methods: This cross-sectional study analyzed 148 patients with T1DM, aged 1-18 years, in Duhok, Kurdistan, Iraq. The study used blood glucose tests, anti-GAD65 antibodies, and HbA1c levels. The University of Zakho's ethical committee approved the study, and IBM SPSS 26 version software was used to analyze the data.

Results: The overall rate of autoantibody positivity was 70 (47.3%), while 78 (52.7%) did not have anti-GAD65 antibodies. The HbA1c was 11.33 ±2.33% on average among individuals who had just received a T1DM diagnosis. The study found no statistically significant association between anti-GAD65 antibody status and HbA1c levels. Although a trend toward higher HbA1c values was observed in anti-GAD65-negative patients, this did not reach statistical significance.

Conclusions: The study found autoantibody positivity in all age groups, with young people having the highest percentage. The results of this study should prompt further statistical analyses to support or negate the results of this study on a larger population scale.

Aldosterone is synthesized in the adrenal zona glomerulosa via the action of the mitochondrial cytochrome P450 enzyme aldosterone synthase (CYP11B2) through sequential enzyme reactions. Pathogenic variants in CYP11B2 result in corticosterone methyloxidase type I deficiency (CMO I), an orphan condition with a potentially lethal electrolyte imbalance in infancy. We report the unique occurrence of CMO I with celiac disease in the first genetically confirmed Polish case of CMO I; a 15-year-old female, diagnosed initially in the neonatal period because of severe hyponatremia, hyperkalemia, metabolic acidosis, and failure to thrive. The patient's clinical course was complicated by protracted electrolyte abnormalities, poor weight gain, and eventual diagnosis of celiac disease, which temporally correlated with abnormal growth patterns. Extensive endocrine assessment, steroid profiling, and next-generation DNA sequencing revealed a homozygous pathogenic variant in CYP11B2 (c.1354G>A; p.Gly452Arg), confirming CMO type I.

Congenital hyperinsulinism (CHI) represents a complex group of genetic disorders causing inappropriate insulin secretion. We report the first case of severe CHI caused by a novel combination of HADH and GHSR mutations, leading to an unusually severe neurological phenotype. A male infant presented at 24 days of life with severe hypoglycemic seizures (0.3 mmol/l), inappropriate hyperinsulinemia (10.31 µUI/ml), and elevated C-peptide (2.64 µg/l). His clinical course was marked by progressive neurological deterioration, evolving from neonatal seizures to West syndrome at 12 months, and subsequently to Lennox-Gastaut syndrome at 3 years. Genetic analysis revealed a previously undescribed combination of a homozygous HADH deletion (5.25 kb, exons 3-4) and a heterozygous GHSR missense variant (c.611C>A, p.Ala204Glu). Therapeutic management was particularly challenging in a resource-limited setting, with unavailability of essential medications such as diazoxide. Despite intensive management with medium-chain triglyceride-enriched formula, levocarnitine, and nocturnal cornstarch, glycemic control remained suboptimal. At 7 years, the patient presents severe psychomotor delay (-4 SD for weight and height) and drug-resistant epilepsy. This case highlights the potential for severe phenotypes in digenic CHI and suggests synergistic effects between fatty acid metabolism and hormonal signaling pathways in glucose homeostasis, opening new perspectives for understanding complex forms of CHI.

Introduction: The study aimed to systematically evaluate whether coronavirus disease (COVID-19) infection and/or vaccination act as environmental triggers for new-onset type 1 diabetes (T1D) in children and adolescents.

Material and methods: We will conduct a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane Library will be searched for studies from 2020 onward. Eligible studies must report new-onset T1D in individuals aged 0-19 years following confirmed SARS-CoV-2 infection or COVID-19 vaccination, with a clearly defined comparator group. Data will be extracted using the Population-Exposure-Comparator-Outcome (PECO) framework, aiming to capture diabetes incidence, diabetic ketoacidosis (DKA) severity, immunologic and genetic markers, direction of effect, and potential confounders. Risk of bias will be assessed with the Newcastle-Ottawa Scale, and GRADE will be used to assess certainty of evidence. A random-effects meta-analysis will be conducted if appropriate.

Expected results: We anticipate mapping the direction of effect (-, ¯, mixed, or = no difference) for each exposure-outcome pair, and identifying gaps related to immunologic markers, diagnostic timing, and confounding factors.

Conclusions: This review will provide a comprehensive synthesis of evidence on infection- and vaccine-triggered pediatric T1D, informing future prospective studies and surveillance efforts.

Introduction: Coeliac disease (CD) often coexists with type 1 diabetes mellitus (T1D). Children with double diagnosis are frequently asymptomatic, which raises the question of whether to introduce a strict gluten-free diet (GFD) or not.

Aim of the study: To summarise data on systemic consequences of coeliac disease in children with type 1 diabetes mellitus.

Material and methods: The PubMed database was searched for papers to identify meta-analyses, reviews and clinical trials focusing on children.

Results: Coeliac disease, like type 1 diabetes may adversely influence glycaemic control, growth, weight gain, lipid profile and bone health as well as increase the risk of vascular complications. A strict gluten-free diet, at least partly, prevents the development of systemic complications of both disorders.

Conclusions: Dietary restrictions do not have a negative impact on the quality of life of young diabetic patients hence a gluten-free diet with its multifaceted beneficial effects should be recommended to all children with diabetes and coeliac disease.

Introduction: Hereditary vitamin D resistant rickets (HVDRR) is a rare autosomal recessive disorder marked by end-organ resistance of 1,25-dihydroxyvitamin D secondary to various mutations in the vitamin D receptor gene. The currently accepted treatment modality involves bypassing the affected receptors in the gut with high-dose intravenous calcium. In a few limited case reports, cinacalcet, a calcimimetic, has been used as an adjunctive therapy.

Material and methods: Retrospective chart reviews were conducted to collect the clinical and biochemical data of 8 patients with HVDRR from 5 Saudi families. Four patients received only high-dose calcium, while the remaining 4 received adjuvant cinacalcet. Serum chemistry and PTH levels were measured before and during cinacalcet treatment. Gene sequencing was performed to identify the disease-causing mutation.

Results: All 8 patients exhibited alopecia and secondary hyperparathyroidism. Other clinical and biochemical features of rickets were present to varying degrees. Genetic analysis revealed 3 distinct mutations: a ligand-binding domain mutation in 3 unrelated patients, a ligand-binding domain mutation in 2 sisters, and a missense DNA-binding domain mutation in 3 brothers. While the overall response to therapy was variable, none of the 4 patients who received adjunctive cinacalcet developed hypocalcaemia, and there was some initial promise in improving serum PTH levels.

Conclusions: This series provides new insight into the clinical and biochemical characteristics as well as treatment responses in Saudi children with HVDRR. The findings suggest that cinacalcet is a safe and potentially valuable adjuvant in this understudied population; however, further research is required to verify these results.

Introduction: Short stature in growth hormone deficiency (GHD) can be treated with recombinant human growth hormone (rhGH), which is proven to be both safe and effective. However, a considerable number of patients does not achieve satisfying therapy outcomes.

Aim of the study: To evaluate the predictive effect of height increase in the first year of rhGH treatment on long-term therapy outcomes.

Material and methods: 165 short-stature children (mean age 10.72 ±3.33 years; 63% males), diagnosed with GHD, treated with rhGH for at least one year (mean follow-up 4.32 ±1.80 years), divided into 2 groups according to the change in height standard deviation score (SDS) after the first year of rhGH treatment: good responders (GR) and poor responders (PR). Then, in one-year intervals, patient's chronological age, bone age, height, weight, insulin-like growth factor level, and rhGH dose were all assessed.

Results: In the GR group, mean height velocity SDS up to five years of observation was 1.19 ±0.41/year and in the PR group 0.59 ±0.38/year. The differences were statistically significant (p < 0.05).

Conclusions: The primary response to the rhGH treatment in GHD children seems to be a good predictor for long-term therapy outcomes.

Introduction: To study the clinical profile and molecular diagnosis of children with severe early-onset non-syndromic monogenic obesity.

Methods: The clinical and molecular data (performed using whole exome sequencing) of 7 children with early-onset (< 5 years) non-syndromic monogenic obesity were extracted from the Obesity Clinic files and analysed retrospectively.

Results: The median (IQR) age at presentation was 18 (10.5-27) months. Of the 7 patients, 5 were boys, 3 had a history of parental consanguinity, and 4 had a family history of severe early-onset obesity. All patients exhibited hyperphagia and showed signs of insulin resistance. Dyslipidaemia and fatty liver were observed in 4. The variants identified in 6 patients included 2 in leptin receptor, and one each in melanocortin 4 receptor, pro-opiomelanocortin, leptin, and neurotrophic tyrosine kinase receptor type 2 genes. Notably, 4 of these variants were novel.

Conclusions: This case series provides valuable insights into the spectrum of genetic mutations associated with non-syndromic monogenic obesity in North Indian children. The findings underscore the significance of next-generation sequencing in identifying the aetiology of severe early-onset obesity.

Currently, hybrid closed loop (HCL) systems represent the most advantageous therapeutic option for people with diabetes requiring intensive insulin therapy. They make it possible to achieve optimal metabolic control of the disease in any age group while improving the quality of life of children and adolescents with diabetes and their families. Therefore, we present recommendations for the use of HCL systems in children and adolescents focusing on systems currently available in Poland. These systems should be the first choice in terms of method of insulin therapy in the paediatric population. They can be implemented at any stage of diabetes management. These recommendations are based on scientific evidence and experts' experience. They include principles for the initiation, optimisation, and ongoing management of HCL therapy, as well as the required HCL-related education.

Introduction: The latest evidence highlights that an unhealthy diet and poor nutrition status are some of the modifiable behavioural risk factors responsible for the development of non-communicable diseases (NCDs). Anti-inflammatory diets are important in both the treatment and prevention of disease (e.g. hypertension, obesity, Hashimoto's thyroiditis). The concept of these diets has common core foundations and recommendations. The family environment from early childhood plays a particularly important role in shaping healthy eating patterns of children and youths. Thus, parents' nutritional knowledge, attitudes, and dietary practices are essential in preventing NCD development and improving their children's health as their primary guardians. This study aims to assess parents' awareness of an anti-inflammatory diet.

Material and methods: A total of 325 parents participated in the study. Data for the study were collected anonymously using the CAWI method. The research tool was an original questionnaire about parents' awareness of anti-inflammatory diets.

Results: Of the 325 parents participating in the study, 204 (62.8%) admitted that they did not know which products to use in an anti-inflammatory diet. About half of them (165; 50.8%) had unsatisfactory knowledge of the anti-inflammatory diet, 66 (30.3%) had a good level of knowledge, and only 16 (5.5%) respondents had an excellent level of knowledge.

Conclusions: Parental awareness of the use of the anti-inflammatory diet was insufficient in the study group. It seems important to implement appropriate educational activities on the anti-inflammatory diet to expand parents' knowledge of the impact of nutrition on children's development.