The effects of gonadotropin-releasing hormone agonist on final adult height among girls with early and fast puberty

IntroductionThis study aimed to explore the impact of gonadotropin-releasing hormone agonists (GnRHa) on final adult height (FAH) in girls with early and fast puberty.MethodsA retrospective study was conducted by reviewing data from the medical records of the Pediatric Endocrinology Clinics between January 1, 2010, and December 31, 2020, at MacKay Children’s Hospital. The treatment group included 109 patients who received 3.75 mg monthly for at least 1 year, whereas the control group consisted of 95 girls who received no treatment.ResultsThe treatment group was significantly older at the time of inclusion(chronological age (CA1), treatment vs. control, 8.7 vs. 8.4 years, p < 0.001), had a more advanced bone age (BA) (BA1, 11.5 vs. 10.8 years, p < 0.001), BA1-CA1 (2.7 vs. 2.2 years, p < 0.001), and shorter predicted adult height (PAH1) (153.3 vs. 157.1 cm, p = 0.005) that was significantly lower than their target height (Tht)(PAH1-Tht, −3.9 vs. −1.3 cm, p = 0.039). The FAHs of the GnRHa and the control group were similar (157.0 vs. 156.7 cm, p = 0.357) and were not significantly different from their Tht (FAH vs. Tht in the GnRHa group, 157.0 vs. 157.0 cm; control group, 156.7 vs. 157.0 cm). In the subgroup analysis, FAH was significantly higher after GnRHa treatment in those with PAH1 less than 153 cm and Tht (154.0 vs. 152.0 cm, p = 0.041), and those whose CA1 was between 8 and 9 years (158.0 vs. 155.4 cm, p = 0.004). We defined satisfactory FAH outcome as FAH-PAH1≥5 cm and significant factors were GnRHa therapy, PAH1 shorter than their Tht, age younger than 9 years, and faster growth velocity during the first year.DiscussionGnRHa is effective in restoring the Tht in some early and fast pubertal girls, especially in those with poorly PAH (PAH lower than 153 cm and shorter than their target height). A younger age at initiation of treatment and a faster growth velocity during treatment are associated with a better height gain

Identification of Novel Susceptibility Loci for Kawasaki Disease in a Han Chinese Population by a Genome-Wide Association Study

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD

The Effect of Self-Efficacy in Self-Management on Diabetes Distress in Young People with Type 2 Diabetes

To understand the relationship among glycemic control, self-efficacy in diabetes management, and diabetes distress in young people with type 2 diabetes, a cross-sectional descriptive study with convenience sampling was designed. A total of 60 young people who had type 2 diabetes (T2D), with 24 (40%) males and 36 (60%) females were included. The mean age was 17.2 and ranged from 10.5 to 24.5 years, and they completed a Perceived Diabetes Self-Management Scale, the Problem Areas in Diabetes Scale and their pharmacologic management and life adjustment. Glycated hemoglobin (HbA1c) was routinely drawn before the outpatient visit. HbA1c and diabetic distress were positively correlated. Self-efficacy was negatively correlated with HbA1c and diabetic distress. In the hierarchical multiple regression analysis, only the duration of illness and self-efficacy remained significant in the final model. The variance for the overall model was 64%, with self-efficacy alone explaining 30% of the variance. In addition, 31.6% of participants had extremely high levels of psychological distress. Conclusions: T2D is an early onset chronic disease, and the young people may have had other health problems, which made the diabetes management a complex process. Nursing staff should regularly assess both the confidence and ability to manage treatment regimen of young people with type 2 diabetes and their psychological distress

Impact of Glycemic Control, Disease Duration, and Exercise on Heart Rate Variability in Children with Type 1 Diabetes Mellitus

Type 1 diabetes is commonly associated with autonomic neuropathy. The present study investigated the influences of glycemic control, disease duration (DD), and exercise on autonomic nervous function in children with type 1 diabetes by analysis of their heart rate variability (HRV). Methods: Seventy-nine type 1 diabetic children were recruited and categorized into four groups by HbA1c of 8% and DD of 4.5 years. HRV parameters as determined by separate frequency domain components (low frequency: LnLF, 0.04–0.15 Hz; high frequency: LnHF, 0.15–0.5 Hz; total power: LnTP, 0.04–0.5 Hz) were measured both at rest and during exercise. Pearson's correlation, one-way ANOVA, and multiple regressions with stepwise method were used for statistical analysis. Results: While at rest, HbA1c and DD were negatively correlated with all HRV parameters. Both HbA1c and DD were significant predictors in LnTP. However, only HbA1c was a significant predictor in LnLF and LnHF. Type 1 diabetes patients with HbA1c > 8% and DD > 4.5 years had a significantly lower HRV than the other patients. During exercise, HRV reduced significantly and no significant correlation between HbA1c and HRV or between DD and HRV was observed. Also, a significant difference in HRV among the four groups was not demonstrated. The smallest decrement in HRV from resting to exercise were in subjects with HbA1c > 8% and DD > 4.5 years. Conclusion: HbA1c was a more dominant predictor for LnTP, LnHF and LnLF than DD in children with type 1 diabetes at rest. HRV reduced significantly from resting to exercise. However, the responses of HRV during exercise differ from the responses of HRV at rest

Genetic Variations in the Kir6.2 Subunit (KCNJ11)

To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading

Mutational Analysis of PTPN11 Gene in Taiwanese Children with Noonan Syndrome

Noonan syndrome (NS) is an autosomal dominant disorder presenting with characteristic facies, short stature, skeletal anomalies, and congenital heart defects. Mutations in protein-tyrosine phosphatase, nonreceptor-type 11 (PTPN11), encoding SHP-2, account for 33-50% of NS. This study screened for mutations in the PTPN11 gene in 34 Taiwanese patients with NS. Mutation analysis of the 15 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the PTPN11 gene. We identified 10 different missense mutations in 13 (38%) patients, including a novel missense mutation (855T > G, F285L). These mutations were clustered in exon 3 (n = 6) encoding the N-SH2 domain, exon 4 (n = 2) encoding the C-SH2 domain, and in exons 8 (n = 2) and 13 (n = 3) encoding the PTP domain. In conclusion, this study provides further support that PTPN11 mutations are responsible for Noonan syndrome in Taiwanese patients. [J Formos Med Assoc 2007;106(2):169-172

Associations between Vitamin D Deficiency and Carbohydrate Intake and Dietary Factors in Taiwanese Pregnant Women

This cross-sectional observation study investigated the vitamin D (VD) status in Taiwanese pregnant women and the effects of VD supplementation and macronutrient intake on serum 25-hydroxy-vitamin D (25[OH]D) level. Data on VD intake, daily sunlight exposure, and carbohydrate intake were obtained from 125 pregnant women at 30–37 weeks’ gestation. Serum 25[OH]D level was measured before delivery in all enrolled women; and the mean 25(OH)D level was 43 nmol/L or 17.2 ng/mL. The 25(OH)D level was significantly correlated with total VD intake of pregnant women (r = 0.239; p = 0.007). The severe VD deficiency group (n = 16; mean of 25(OH)D level = 8.5 ng/mL) had significantly lower total VD intake and supplementation than the groups with VD deficiency (n = 69), insufficiency (n = 32), and sufficiency (n = 8). Those with ≥400 IU/day total VD intake (including VD from food and supplementation) had significantly higher 25(OH)D concentration than those with p = 0.031). In conclusion, VD deficiency was highly prevalent in Taiwanese pregnant women. VD supplementation was the most effective method for increasing 25(OH)D concentration in pregnant women. Higher carbohydrate intake might reduce 25(OH)D levels

Acute kidney injury is a common complication in children and adolescents hospitalized for diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is associated with dehydration and which can cause acute kidney injury (AKI). The proportion of AKI in children and adolescents with DKA has not been reported in East Asian population. This study aimed to identify the prevalence of AKI and to determine whether there is an association between AKI severity and recovery time from metabolic acidosis in children and adolescents with DKA. Medical records of children and adolescents (aged 1.5 times the calculated expected baseline creatinine level. Patients were divided into three groups based on AKI severity: no AKI, mild AKI, and severe AKI. In total, 170 (56.5%) patients with DKA presented AKI (mild AKI, 116 [38.5%]; severe AKI, 54 [18.0%]). Heart rate and laboratory parameters related to dehydration, such as corrected sodium level and blood urea nitrogen, were strongly associated with AKI development (P<0.01). Blood pH, plasma glucose, and potassium levels were also associated with AKI. A negative correlation with borderline significance between the estimated glomerular filtration rate (eGFR) and recovery time from metabolic acidosis was observed in the severe AKI group. AKI was highly prevalent in children and adolescents with DKA. An association between AKI and biomarkers indicating dehydration was noted. The recovery time from metabolic acidosis following treatment may be longer in children with a decreased eGFR who present with severe AKI. AKI is a common complication in children with DKA