Journal of Clinical Research in Pediatric Endocrinology最新文献

Objective: Mild metabolic acidosis may adversely affect cardiovascular risk factors, and diet-dependent acid-base load may impair mental health and sleep quality. The aim of this study was to investigate the effects of dietary acid load on cardiometabolic risk factors, psychological resilience, and sleep quality in adolescents with obesity.

Methods: 205 adolescents with obesity (105 males, 100 females) aged 13-18 years participated in the study. Participants' biochemical parameters, anthropometric measurements and blood pressures were measured. Three-day retrospective food intake records were collected from the adolescents, and potential renal acid load (PRAL), net endogenous acid production (NEAP), and dietary acid load (DAL) were derived from food intake records. Psychological resilience levels of adolescents were assessed by the Child and Youth Resilience Measure (CYRM-12) and sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI).

Results: It was found that BMI, fat mass, fat percentage, fasting insulin, triglyceride, systolic blood pressure, HOMA-IR and PSQI scores were significantly higher and psychological resilience levels were significantly lower in high tertiles of dietary acid load (p<0.05). Adolescents in the lowest tertile of dietary acid load scores had higher consumption of whole grains, vegetables, dairies, legumes, and higher intakes of potassium and calcium than adolescents in the highest tertile of the dietary acid load scores (p<0.05). Red meat, white meat consumption and sodium intake were higher in adolescents in the high tertiles (p<0.05). Energy intakes were found to be significantly lower in the first tertile of PRAL and DAL scores compared to the other tertiles (p<0.05). According to the linear regression model, an increase in NEAP, PRAL and DAL scores leads to a decrease in psychological resilience score and an increase in PSQI and HOMA-IR scores (p<0.05).

Conclusion: High dietary acid load is associated with high cardiometabolic risk, insulin resistance, and low psychological resilience and poor sleep quality.

Objective: Childhood obesity is associated with long-term health complications. Liraglutide is approved for use in adolescents for weight loss and has shown beneficial outcomes in clinical trials. Continuous glucose monitoring (CGM) is routinely used in type 1 diabetes mellitus. We aimed to look at the effect of liraglutide treatment on cardiometabolic variables, glycaemic control (as assessed by CGM), body composition, quality-of-life and satiety levels in adolescents with severe obesity.

Methods: 24 patients aged 12 to 17.9 years (10M:14F) were commenced on liraglutide in addition to lifestyle support. PedsQL 4.0 generic scale and Three-factor Eating Questionnaire R18 were completed at baseline and 3-months.

Results: Significant improvements were shown in weight, body mass index, body mass index standard deviation scores, percentage body fat and fat mass following liraglutide treatment. A significant reduction in HbA1c, triglyceride and cholesterol levels, as well as a reduction in uncontrolled eating behaviour were observed. When compared to the healthy adolescents, the time spent within normal glucose range (3.9-7.8mmol/L; 70.2-140.4 mg/dL) remained low (91.76% vs 97.00%) at baseline but improved after liraglutide treatment. Our results showed lower health-related quality-of-life scores and higher uncontrolled eating and emotional eating behaviours, compared to the healthy population.

Conclusion: We report, for the first time, the role of CGM in identifying glycaemic dysregulation in children and young people with obesity before and after liraglutide treatment. The results have shown significant potential for liraglutide treatment in improving the outcomes. Earlier identification of glycaemic dysregulation and targeted therapy could potentially reduce the long-term risk of developing T2DM.

Successful management of type 1 diabetes (T1D) requires not only optimal glycemic outcomes, but also a holistic approach that encompasses all aspects of life and recommendations to address needs. Current goals include optimal glycemic values, quality of life and life expectancy similar to peers, prevention of long-term complications, prevention of severe hypoglycemia as far as possible and facilitation of glucose management. The International Society for Pediatric and Adolescent Diabetes (ISPAD) has been updating its guidelines for diabetes care every four years since 1995, covering more and more topics. For optimal metabolic outcomes, diabetes teams need to follow these current recommendations, adapt them to their clinical practice and provide guidance to people with T1D and their families. In this review, in the light of ISPAD 2018-2022 guidelines and clinical experiences, “10 Key Recommendations”, emphasizing the importance of teamwork and the use of technology, current T1D treatment is described for practical applications.

Diabetic neuropathy is a major cause of morbidity among diabetics, usually affecting patients with long-standing diabetes and advancing age. We present a case of atypical first clinical presentation of type 1 diabetes mellitus (T1DM) in a pediatric patient. A 15-year-old male patient presented to the emergency department with complaints of right foot weakness associated with mild paresthesia of 1-week duration. There were complaints of polyuria, polydipsia and weight loss in the same timeframe. On subsequent examination, the patient exhibited signs of right-sided foot drop with weak ankle dorsiflexion and eversion, accompanied by impaired sensation over the dorsum of the right foot. Lab results confirmed a diagnosis of T1DM and the patient was started on subcutaneous insulin injections. The patient’s foot drop recovered within one month of insulin initiation. This case highlights that T1DM may present atypically as acute onset neuropathy in pediatric patients, making it an important differential diagnosis.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a disease in which neurological findings are dominant due to deficiencies in neurotransmitter synthesis. Hypoglycemia caused by autonomic dysfunction is one of the symptoms that may be encountered. Here we report a case of mild AADC deficiency presenting with hypoglycemia without any neurological signs. A 4-year-old girl presented with recurrent hypoglycemia. Her growth and development were normal. Plasma insulin and cortisol values were normal in the sample at the time of hypoglycemia. C8:1-Carnitine elevation was detected in the acylcarnitine profile. A clinical exome panel was performed with the suggestion of a fatty acid oxidation defect. However, a homozygous variant in the DDC gene was detected. Furthermore, cerebrospinal fluid neurotransmitter analysis revealed low 5-hydroxyindolacetic acid and homovanillic acid and high 3-O-methyl-dopa and methyltetrahydrofolate (5 MTHF) consistent with AADC deficiency. Plasma AADC enzyme activity was low. The episodes of hypoglycemia were treated with uncooked cornstarch. This case suggests that AADC deficiency should be considered in some patients with hypoglycemia.

Objective: Disorders of glucose metabolism in children with obesity are less common than in adults. There is also evidence that they may be transient. The aims of this study were to determine the prevalences of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (DM2) and its reversibility in pediatric patients with obesity and to define the factors determining the reversibility of prediabetes or progression to diabetes.

Methods: Retrospective analysis included of young patients with obesity. Patients presented and were treated between 2000-2022 at a single center.

Results: The study included 573 (316 girls; 55.15%) Caucasian patients with median body mass index (BMI) Z-score of 3.95 (range 2.0-9.9) and median age 13.9 (2.9-17.1) years old. OGTT results were normal in 90.8% (n=520) and signs of prediabetes occurred in 9.2% (n=53); IFG 17%, IGT 88.7%, DM 0%. Among those who underwent OGTT twice (n=53), impaired glucose regulation was present in 9.3% (n=5) (IFG 40%, IGT 80%, DM 0%) at baseline and in 14.8% subject (n=8) (IFG 25%, IGT 50%, DM 25%) at follow-up after lifestyle modification only. After 12-36 months of follow up, in those with a history of IGT, 60% reverted to normal glucose tolerance, while IFG and IGT persisted in 20% and 20%, respectively, and none progressed to DM. The risk factors for progression of glucose metabolism disorders were increase of BMI Z-score, higher insulin levels and elevated homeostatic model assessment-insulin resistance.

Conclusion: IFG and IGT are common in pediatric patients with obesity, while the progression to DM2 is rare. Disorders of glucose metabolism have reversible character.

Objective: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years.

Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis.

Results: Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m², p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m², p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m², p<0.001).

Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide.

Objective: Maturity onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY.

Methods: MODY cases from 14 different pediatric endocrinology departments were included. Diagnosis, treatment, follow-up data, and results of genetic analysis were evaluated.

Results: A total of 224 patients were included, of whom 101 (45%) were female, and the mean age at diagnosis was 9.4±4.1 years. Gene variant distribution was: 146 (65%) GCK; 43 (19%) HNF1A; 8 (3.6%) HNF4A, 8 (3.6%) KLF11 and 7 (3.1%) HNF1B. The remaining 12 variants were: PDX (n=1), NEUROD1 (n=3), CEL (n=1), INS (n=3), ABCC8 (n= 3) and KJNC11 (n=1). Of the cases, 197 (87.9%) were diagnosed with incidental hyperglycemia, 16 with ketosis (7%) and 7 (3%) with diabetic ketoacidosis (DKA), while 30% presented with classical symptoms of diabetes. Two-hundred (89%) had a family history of diabetes. Anti-GAD antibody was detected in 13 cases, anti-islet antibody in eight and anti-insulin antibody in four. Obesity was present in 16. Distribution of therapy was: 158 (71%) diet only; 23 (11%) intensive insulin treatment; 17 (7.6%) sulfonylureas; 10 (4.5%) metformin; and 6 (2.7%) insulin and oral anti-diabetic treatment.

Conclusion: This was the largest genetically diagnosed series from Turkey. The most common gene variants were GCK and HNF1A with much lower proportions for other MODY types. Hyperglycemia was the most common presenting symptom while 11% of patients had diabetes-associated autoantibodies and 7% were obese. The majority of patients received dietary management only.

Objective: Differentiated thyroid cancer (DTC) is the most common pediatric endocrine cancer but studies are scarce. Latest recommendations advocate for an individualized risk-based approach to select patients for additional therapy. Lymphovascular invasion is not considered, despite being a well-known risk factor in the adult population. The aim of this study was to describe the outcomes of a cohort of DTC patients diagnosed at pediatric age and to evaluate the impact of lymphovascular invasion on the risk of persistence/recurrence.

Methods: A retrospective study of patients diagnosed with DTC at pediatric age from 2010 to 2022 at a single center was performed. All patients had total thyroidectomy. Radioactive iodine therapy (RAI) was used in selected patients. The response to therapy and occurrence of persistent/recurrent disease were evaluated.

Results: A total of 21 DTC were diagnosed, mostly papillary thyroid carcinoma (PTC) (81.0%, n=17). Six patients (28.6%) had nodal involvement and one (4.8%) had lung metastasis at the time of the diagnosis. Lymphovascular invasion was present in 11 patients (52.4%). After surgery, 13 patients (61.9%) underwent RAI. The mean follow-up time was 5.7±3.1 years. In total, 6 patients (31.6%) experienced persistent/recurrent disease during the follow-up time. Among PTC patients, persistent/recurrent disease was more frequent in the presence of lymphovascular invasion [55.6% (5/9) vs. 0.0% (0/6), p=0.031].

Conclusion: An individualized risk-based approach is recommended. Our study suggests that lymphovascular invasion may be associated with a higher risk of persistence/recurrence and should therefore be considered for decision making in children and adolescents with PTC.

Objective: Treatment adherence is crucial for the success of growth hormone (GH) therapy. Reported non-adherence rates in GH treatment have varied widely. Several factors may have an impact on adherence. Apart from these factors, the global impact of the Coronavirus disease-2019 (COVID-19) pandemic, including problems with hospital admission and routine follow-up of patients using GH treatment, may have additionally affected the adherence rate. The primary objective of this study was to investigate adherence to treatment in patients receiving GH. In addition, potential problems with GH treatment during the pandemic were investigated.

Methods: This was a multicenter survey study that was sent to pediatric endocrinologists during the pandemic period (June-December 2021). Patient data, diagnosis, history of pituitary surgery, current GH doses, duration of GH therapy, the person administering therapy (either parent/patient), duration of missed doses, reasons for missed doses, as well as problems associated with GH therapy, missed dose data and the causes in the recent year (after the onset of the pandemic) were questioned. Treatment adherence was categorized based on missed dose rates over the past month (0 to 5%, full adherence; 5.1 to 10% moderate adherence; >10% non-adherence).

Results: The study cohort consisted of 427 cases (56.2% male) from thirteen centers. Median age of diagnosis was 8.13 (0.13-16) years. Treatment indications were isolated GH deficiency (61.4%), multiple pituitary hormone deficiency (14%), Turner syndrome (7.5%), idiopathic GH deficiency (7.5%), small for gestational age (2.8%), and “others“ (6.8%). GH therapy was administered by parents in 70% and by patients in 30%. Mean daily dose was 32.3 μg/kg, the annual growth rate was 1.15 standard deviation score (minimum -2.74, maximum 9.3). Overall GH adherence rate was good in 70.3%, moderate in 14.7%, and poor in 15% of the patients. The reasons for non-adherence were mainly due to forgetfulness, being tired, inability to access medication, and/or pen problems. It was noteworthy that there was a negative effect on adherence during the COVID-19 pandemic reported by 22% of patients and the main reasons given were problems obtaining an appointment, taking the medication, and anxiety about going to hospital. There was no difference between genders in the adherence rate. Non-adherence to GH treatment decreased significantly when the patient: administered the treatment; was older; had longer duration of treatment; and during the pandemic. There was a non-significant decrease in annual growth rate as non-adherence rate increased.

Conclusion: During the COVID-19 pandemic, the poor adherence rate was 15%, and duration of GH therapy and older age were important factors. There was a negative effect on adherence during the pandemic period.