Trends in HOMA-IR values among South Korean adolescents from 2007-2010 to 2019-2020: a sex-, age-, and weight status-specific analysis.

BACKGROUND/OBJECTIVES: An increase in obesity prevalence may lead to an increase in the HOMA-IR value. This study aimed to investigate changes in age- and sex-specific homeostasis model assessment of insulin resistance (HOMA-IR) values among South Korean adolescents, using data from the Korean National Health and Nutrition Examination Survey (KNHANES) IV, V, and VIII conducted between 2007-2010 and 2019-2020. SUBJECTS/METHODS: Overall, 4621 adolescents aged 10-18 years were evaluated, including 3473 from the 2007-2010 dataset and 1148 from the 2019-2020 dataset. The mean HOMA-IR values and percentile curves were evaluated by age, sex, and weight status. RESULTS: The mean HOMA-IR values peaked at puberty in both sexes and further increased during puberty in the 2019-2020 dataset (boys 5.21, 95% confidence interval [CI] 4.16-6.26; girls 5.21, 95% CI 3.09-7.33) compared with the 2007-2010 dataset (boys 3.25, 95% CI 3.04-3.47; girls 3.58, 95% CI 3.31-3.85). Both groups (with normal-weight and overweight/obesity) exhibited a peak HOMA-IR value during puberty in both sexes and both datasets, although the group with overweight/obesity had a higher and wider peak age range. While the mean HOMA-IR values did not change in adolescents with normal-weight, they increased during puberty and post-puberty in boys with overweight/obesity. CONCLUSIONS: HOMA-IR values should be interpreted considering sex, weight status, and pubertal stages. In particular, during the pubertal period, insulin resistance (IR) can coexist not only due to weight-related factors but also as a result of the distinct hormonal changes characteristic of puberty. Over the 10-year period, the mean HOMA-IR values increased in the group with overweight/obesity during puberty and post-puberty, highlighting the need for active intervention to prevent metabolic complications in adolescents with overweight/obesity.

The Genotype-Phenotype Correlation in Human 5α-Reductase Type 2 Deficiency: Classified and Analyzed from a SRD5A2 Structural Perspective.

The phenotype of the 5α-reductase type 2 deficiency (5αRD2) by the SRD5A2 gene mutation varies, and although there have been many attempts, the genotype-phenotype correlation still has not yet been adequately evaluated. Recently, the crystal structure of the 5α-reductase type 2 isozyme (SRD5A2) has been determined. Therefore, the present study retrospectively evaluated the genotype-phenotype correlation from a structural perspective in 19 Korean patients with 5αRD2. Additionally, variants were classified according to structural categories, and phenotypic severity was compared with previously published data. The p.R227Q variant, which belongs to the NADPH-binding residue mutation category, exhibited a more masculine phenotype (higher external masculinization score) than other variants. Furthermore, compound heterozygous mutations with p.R227Q mitigated phenotypic severity. Similarly, other mutations in this category showed mild to moderate phenotypes. Conversely, the variants categorized as structure-destabilizing and small to bulky residue mutations showed moderate to severe phenotypes, and those categorized as catalytic site and helix-breaking mutations exhibited severe phenotypes. Therefore, the SRD5A2 structural approach suggested that a genotype-phenotype correlation does exist in 5αRD2. Furthermore, the categorization of SRD5A2 gene variants according to the SRD5A2 structure facilitates the prediction of the severity of 5αRD2 and the management and genetic counseling of patients affected by it.

Comparison of the Triglyceride Glucose Index and Modified Triglyceride Glucose Indices to Predict Nonalcoholic Fatty Liver Disease in Youths.

OBJECTIVE: To assess the associations between the triglyceride glucose (TyG) index and modified TyG indices with nonalcoholic fatty liver disease (NAFLD) and evaluate their ability as predictors of NAFLD in youths. STUDY DESIGN: We analyzed the cross-sectional data of 3728 individuals aged 10-19 years using the Korea National Health and Nutrition Examination Survey, a nationally representative survey. Logistic regression analysis was performed, and ORs and 95% CIs of tertiles 2 and 3 for each variable for predicting NAFLD were calculated and compared with those of tertile 1 as the reference. Receiver operating characteristic (ROC) curves were plotted to evaluate the ability of each variable for NAFLD prediction. RESULTS: All TyG and modified TyG indices exhibited progressively increased ORs and 95% CIs for NAFLD across all tertiles (all P < .001). In addition, all TyG and modified TyG indices significantly predicted NAFLD through ROC curves. All modified TyG indices were superior to the TyG index for predicting NAFLD in all subjects and in males. Among females, the TyG-waist-to-height ratio was superior to the TyG index, TyG-body mass index (BMI), and TyG-waist circumference (WC), and the TyG-BMI SDS and TyG-WC were superior to the TyG index. CONCLUSIONS: The TyG and modified TyG indices are markers for NAFLD prediction in youths, and the modified TyG indices are superior to the TyG index. Modified TyG indices have the potential to be simple and cost-effective markers in screening for NAFLD in youths.

Trends of Dyslipidemia in Korean Youth According to Sex and Body Mass Index: Based on the Korea National Health and Nutrition Examination Survey (2007-2018).

OBJECTIVE: To assess trends of dyslipidemia among youth, we investigated secular trends in serum lipid levels from 2007 to 2018 and the current prevalence of dyslipidemia in Korean children and adolescents. STUDY DESIGN: This cross-sectional study investigated lipid profiles of 10 734 youths aged 10-18 years using data from phases IV-VII of the Korea National Health and Nutritional Examination Survey. We assessed age-, sex-, and body mass index (BMI)-adjusted mean levels of lipids at each survey. RESULTS: Mean levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) levels increased from phase IV to VII. Among boys, the prevalence of acceptable levels of total cholesterol, LDL-C, and non-HDL-C decreased significantly (P = .005, P = .001, and P < .001, respectively). In girls, the prevalence of acceptable levels of total cholesterol, LDL-C, HDL-C, and non-HDL-C decreased significantly (P = .003, P = .005, P = .008, and P = .013, respectively). In BMI- and age-specific analyses, worsening trends in total cholesterol, LDL-C, and non-HDL levels were more apparent in youths with a normal BMI and young age. CONCLUSIONS: Dyslipidemia trends are worsening in Korean youth, even in those with a normal BMI and young age. Thus, future cardiovascular disease risk may increase and comprehensive management plans are required for youth with overweight or obesity and those with a normal BMI and young age.

Recombinant growth hormone therapy in children with Turner Syndrome in Korea: a phase III Randomized Trial.

BACKGROUND: Short stature is the most consistent characteristic feature of Turner syndrome (TS). To improve final heights of children with TS effectively, it is important to provide them with early and appropriate treatment using growth hormone (GH). The objective of this study was to assess the efficacy and safety of a new recombinant human GH, Growtropin®-II (DA-3002, Dong-A ST Co., Ltd) versus a comparator (Genotropin®, Pfizer Inc.) for Korean children with TS. METHODS: This open-label, active-controlled, parallel-group, randomized controlled phase III trial was conducted at 11 hospitals in Korea. Eligible patients (n = 58) were randomized to two groups: 1) DA-3002 group (administrated with DA-3002 at 0.14 IU [0.0450-0.050 mg] /kg/day); and 2) comparator group (administrated with the comparator at 0.14 IU [0.0450-0.050 mg] /kg/day). RESULTS: The change from baseline in annualized height velocity (HV) after a 52-week treatment period was 4.15 ± 0.30 cm/year in the DA-3002 group and 4.34 ± 0.29 cm/year in the comparator group. The lower bound of 95% two-sided confidence interval for group difference in the change of annualized HV (- 1.02) satisfied the non-inferiority margin (- 1.5). The change in height standard deviation score (HtSDS) at 52-week was 0.70 ± 0.23 for the DA-3002 group and 0.66 ± 0.39 for the comparator group, showing no significant (p = 0.685) difference between the two groups. The change of skeletal maturity defined as change in bone age/change in chronological age between the two groups was not significantly different (1.25 ± 0.58 for the DA-3002 group and 1.47 ± 0.45 for the comparator group, p = 0.134). Changes from baseline in serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) after 52 weeks of treatment did not differ significantly between the two groups (p = 0.565 and p = 0.388, respectively) either. The occurrence of adverse events was not statistically different between groups. CONCLUSIONS: This study demonstrates that the efficacy and safety of GH treatment with DA-3002 in children with TS are comparable with those of the comparator. It is expected to analysis the long-term effect of DA-3002 on the increase of final adult height in children with TS and possible late-onset complications in the future. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov. ClinicalTrials.gov identifier: NCT01813630 (19/03/2013).

Central precocious puberty may be a manifestation of endocrine dysfunction in pediatric patients with mitochondrial disease.

We retrospectively reviewed the data of 140 female pediatric patients with rare mitochondrial diseases (MDs) confirmed using muscle biopsy. We evaluated patients who were diagnosed with central precocious puberty (PP) with early pubertal development to determine whether PP is a clinical manifestation of MDs. We also examined the clinical, auxiological, laboratory, and radiological parameters after 1 year of gonadotropin-releasing hormone treatment for central PP. Among the 140 girls with MDs, 29 had early pubertal development and underwent endocrine evaluation. Ten (7.1%) patients were diagnosed with central PP; the prevalence of central PP was higher than was that previously thought. Patients with central PP exhibited bone age advancement over 1 year and increased sex hormone levels despite their young age at diagnosis. Serum estradiol levels were significantly higher in younger patients than in older patients (P = 0.004). Patients with central PP treated with gonadotropin-releasing hormone had favorable outcomes, and their pubertal development was suppressed for 1 year.Conclusion: Central PP may be a manifestation of endocrine dysfunction in young girls with MDs. What is Known: • The general characteristics of mitochondrial diseases include developmental delays and retarded growth. • Precocious puberty has rarely been suggested as a clinical manifestation of mitochondrial diseases. What is New: • Among the 140 girls with mitochondrial diseases, 10 (7.1%) were diagnosed with central precocious puberty. • Serum estradiol levels were significantly higher in younger patients than in older patients.

High Prevalence of Nonalcoholic Fatty Liver Disease Among Adolescents and Young Adults With Hypopituitarism due to Growth Hormone Deficiency.

OBJECTIVE: To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) in adolescents and young adults with hypopituitarism and to examine the associations of growth hormone (GH) deficiency with the occurrence of NAFLD. METHODS: A cross-sectional study for the determination of NAFLD prevalence included 76 patients with childhood-onset hypopituitarism and 74 controls matched by age and body mass index (BMI). We investigated the prevalence of NAFLD in adolescent and young adult patients with hypopituitarism as well as the age- and BMI-matched controls. Among patients with hypopituitarism, anthropometric, clinical, and biochemical assessments using transient elastography and magnetic resonance imaging were performed. Logistic regression was used to identify the factors associated with NAFLD. RESULTS: The adolescents and young adults with hypopituitarism exhibited higher prevalence of NAFLD than the age- and BMI-matched controls. Among patients with hypopituitarism, obesity and obesity-related metabolic derangements were significantly associated with liver steatosis and fibrosis, whereas lower insulin-like growth factor (IGF)-I standard deviation score (SDS) and IGF-I/IGF-binding protein 3 molar ratios were associated with steatosis. In regression analyses adjusted for BMI SDS, steatosis was found to be associated with a lower IGF-I SDS and IGF-I/IGF-binding protein 3 molar ratios, whereas liver fibrosis was found to be associated with a lower IGF-I SDS. CONCLUSION: Our results suggest that GH deficiency contributes to the occurrence of NAFLD, along with obesity and obesity-related metabolic changes. Because NAFLD occurs early in patients with hypopituitarism, the surveillance, weight control, and timely replacement of deficit hormones, including GH, are essential.

Adolescents with thyroid nodules: retrospective analysis of factors predicting malignancy.

Thyroid nodules are less common in children than in adults. However, pediatric thyroid nodules have a higher rate of malignancy compared to those in adults, and increased risk of metastasis and recurrence. In the present study, we analyzed the clinical features as well as laboratory and thyroid ultrasound (US) findings of children and adolescents with thyroid nodules to identify predictive factors of thyroid cancer. We retrospectively analyzed 275 patients with thyroid nodules under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2017. Among them, 141 patients who underwent ultrasonography-guided fine needle aspiration biopsy (FNAB), and four patients without FNAB who underwent surgical resection, were included in this study. The remaining 125 patients without FNAB and five patients with follow-up loss after FNAB were excluded. Clinical, laboratory, and US data were evaluated in 145 patients to establish the potential predictive factors of thyroid cancer. Thyroid malignancies were observed in 101 patients. Grade 2 goiters were seen more often in benign nodule group. Hypoechoic nodules, nodules with microcalcifications, abnormal lymph nodes, and irregular margins were findings significantly associated with thyroid cancer. The findings of hypoechoic nodule, nodule with microcalcifications, and abnormal lymph nodes showed statistical significance in predicting thyroid cancer.Conclusion: Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in children. Therefore, further diagnostic evaluations, including FNAB, should be considered in patients with such findings.What is Known:• Thyroid nodules are less common in children than in adults, but pediatric thyroid nodules have a higher rate of malignancy, and also have increased risk of metastasis and recurrence.• Research on ways to predict thyroid cancer have mostly been accomplished in adult patients, and the application of risk stratification system has not been fully satisfactory in children, which requires further studies in pediatric thyroid nodules.What is New:• Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in Korean children.

Incidence and Prevalence of Central Precocious Puberty in Korea: An Epidemiologic Study Based on a National Database.

OBJECTIVES: To investigate the prevalence and incidence of central precocious puberty in Korea using claims data provided by the Health Insurance Review and Assessment Service in Korea as the population-based epidemiologic study. STUDY DESIGN: In this national registry-based, longitudinal, epidemiologic study, patients who were registered with an International Classifications of Diseases, Tenth Revision diagnosis of central precocious puberty (E22.8 according to International Classifications of Diseases, Tenth Revision) and treated with gonadotropin-releasing hormone agonist were included. We assessed the age- and sex-specific prevalence and incidence rates of central precocious puberty in Korea from 2008 to 2014. RESULTS: A total of 37 890 girls and 1220 boys were newly registered with a diagnosis of central precocious puberty from 2008 to 2014. The overall incidence of central precocious puberty during the study period was 122.8 per 100 000 persons (girls, 262.8; boys, 7.0). The overall prevalence of central precocious puberty during the study period was 193.2 per 100 000 persons (girls, 410.6; boys, 10.9). The incidence and prevalence of central precocious puberty steeply increased during the study period in both girls and boys. CONCLUSIONS: This epidemiologic study, based on a national registry that included Korean children, demonstrated that the incidence and prevalence rates of central precocious puberty were high and increased steeply during the study period. Further investigations to determine the underlying causes for this rapid increase in central precocious puberty are needed.

The analysis of endocrine disruptors in patients with central precocious puberty.

BACKGROUND: A few studies have reported a positive association between phthalate exposure and pubertal timing, but several conflicting reports exist. The main objective of the study was to determine whether phthalate exposure was associated with central precocious puberty in girls. METHODS: This was a multicenter case-control study wherein 47 girls with central precocious puberty (CPP) and 47 controls (26 pre-pubertal girls and 21 pubertal girls) were enrolled. No obese girls were included. Five phthalate metabolites (creatinine adjusted) and bisphenol A (BPA) were measured in the first spot urine samples of these 94 girls in the early morning. RESULTS: The median values of monobenzyl phthalate (MBzP), mono-2-ethyl-5-carboxypentyl phthalate (MECPP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-ethyl-5-oxohexyl phthalate (MEOHP), and mono-n-butyl phthalate (MnBP) were 3.1, 29.3, 18.0, 15.4, and 25.2 µg/g creatinine in the CPP group, 4.3, 53.7, 35.7, 29.1, and 66.0 µg/g creatinine in the pre-pubertal control group, and 1.7, 28.7, 21.4, 12.1, and 33.3 µg/g creatinine in the pubertal control group, respectively. The urinary concentration of the five phthalates was significantly lower in the CPP group than in the pre-pubertal control group (P < 0.001). Conversely, there was no significant difference in the urinary concentration of the five phthalates between the CPP and pubertal control groups (P values: 0.077 for MBzP, 0.733 for MECPP, 0.762 for MEHHP, 0.405 for MEOHP, and 0.981 for MnBP). In addition, the BPA level was not significantly different between the CPP and pubertal control groups (BPA median values: 0.63 µg/g creatinine, the CPP group; 1.7 µg/g creatinine, the pubertal control group; P value = 0.092). CONCLUSIONS: Our study showed that there was no significant difference in the urinary phthalate levels between the CPP and pubertal control groups. Moreover, phthalate metabolites were significantly lower in the CPP group than in the pre-pubertal control group. Further investigation about endocrine disruptors and pubertal progression is needed.

Healthcare Transition Readiness, Family Support, and Self-management Competency in Korean Emerging Adults with Type 1 Diabetes Mellitus.

PURPOSE: The current study investigated factors related to healthcare transition readiness, including family support and self-management competency, in emerging adults with Type 1 diabetes mellitus (T1DM). DESIGN AND METHODS: A cross-sectional survey was conducted with 87 individuals, aged 16-24 years. Participants were recruited both from the outpatient clinic of Severance Children's Hospital, and an online self-help group for emerging adults with T1DM in South Korea. Participants reported perceived levels of family support, self-management competency, and healthcare transition readiness through a structured questionnaire. RESULTS: Healthcare transition readiness was positively correlated with family support (r = 0.257, p = .016) and self-management competency (r = 0.606, p < .001). Multivariate linear regression analyses revealed that only self-management competency was a significant factor associated with healthcare transition readiness (ß = 0.699, p < .001). CONCLUSIONS: For emerging adults with T1DM, ongoing family involvement in diabetes care and enhanced self-management competency can strengthen their healthcare transition readiness. Furthermore, primary factors associated with healthcare transition readiness in the present study were identified as self-management competency and participants' age. PRACTICE IMPLICATIONS: Healthcare providers should assess and enhance healthcare transition readiness in emerging adults with T1DM. A primary method of addressing transition readiness is helping people strengthen their self-management competency.

Elevated serum YKL-40 levels in patients with Kawasaki disease.

CONTEXT: YKL-40 is an inflammatory biomarker for endothelial dysfunction that may have a role in Kawasaki disease (KD). OBJECTIVES: We investigated the association of serum YKL-40 levels with KD and established laboratory parameters for YKL-40 levels and other inflammatory markers. METHODS: YKL-40 levels and other inflammatory markers of 23 KD patients, 9 disease control patients and 11 age-matched healthy controls. RESULTS: YKL-40 concentration in the serum of KD patients significantly increased during the acute disease phase compared with those of disease controls and healthy controls. CONCLUSIONS: Increased YKL-40 levels may provide a useful inflammatory marker for patients with KD.

Intratumoral heterogeneity of (18)F-FDG uptake predicts survival in patients with pancreatic ductal adenocarcinoma.

PURPOSE: To assess whether intratumoral heterogeneity measured by (18)F-FDG PET texture analysis has potential as a prognostic imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We evaluated a cohort of 137 patients with newly diagnosed PDAC who underwent pretreatment (18)F-FDG PET/CT from January 2008 to December 2010. First-order (histogram indices) and higher-order (grey-level run length, difference, size zone matrices) textural features of primary tumours were extracted by PET texture analysis. Conventional PET parameters including metabolic tumour volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) were also measured. To assess and compare the predictive performance of imaging biomarkers, time-dependent receiver operating characteristic (ROC) curves for censored survival data and areas under the ROC curve (AUC) at 2 years after diagnosis were used. Associations between imaging biomarkers and overall survival were assessed using Cox proportional hazards regression models. RESULTS: The best imaging biomarker for overall survival prediction was first-order entropy (AUC = 0.720), followed by TLG (AUC = 0.697), MTV (AUC = 0.692), and maximum SUV (AUC = 0.625). After adjusting for age, sex, clinical stage, tumour size and serum CA19-9 level, multivariable Cox analysis demonstrated that higher entropy (hazard ratio, HR, 5.59; P = 0.028) was independently associated with worse survival, whereas TLG (HR 0.98; P = 0.875) was not an independent prognostic factor. CONCLUSION: Intratumoral heterogeneity of (18)F-FDG uptake measured by PET texture analysis is an independent predictor of survival along with tumour stage and serum CA19-9 level in patients with PDAC. In addition, first-order entropy as a measure of intratumoral metabolic heterogeneity is a better quantitative imaging biomarker of prognosis than conventional PET parameters.

Influence of bottle-feeding on serum bisphenol a levels in infants.

Exposure to endocrine disrupting chemicals (EDCs), particularly during developmental periods, gives rise to a variety of adverse health outcomes. Bisphenol A (BPA) is a well-known EDC commonly found in plastic products including food and water containers, baby bottles, and metal can linings. This study investigates infant exposure to BPA and the effect of bottle-feeding on serum BPA levels in infants. Serum BPA levels in normal healthy infants 6 to 15 months of age (n=60) were evaluated by a competitive ELISA. BPA was detected in every study sample. Serum BPA levels of bottle-fed infants (n=30) were significantly higher than those of breast-fed infants (n=30) (96.58±102.36 vs 45.53±34.05 pg/mL, P=0.014). There were no significant differences in serum BPA levels between boys (n=31) and girls (n=29). No significant correlations were found between serum BPA levels and age, body weight, birth weight, and gestational age. Bottle-feeding seems to increase the risk of infant exposure to BPA. Establishment of health policies to reduce or prevent BPA exposure in infants is necessary.

KISS1 gene polymorphisms in Korean girls with central precocious puberty.

Kisspeptin/G-protein couple receptor-54 (GPR54) system plays a key role in the activation of the gonadotropic axis at puberty. Central precocious puberty (CPP) is caused by the premature activation of hypothalamic gonadotropin-releasing hormone secretion. This study was aimed to identify KISS1 gene variations and to investigate the associations between KISS1 gene variations and CPP in Korean girls. All coding exons of KISS1 gene were sequenced in Korean girls with CPP (n = 143) and their healthy controls (n = 101). Nine polymorphisms were identified in KISS1 gene. A novel single-nucleotide polymorphism (SNP), 55648176 T/G, was identified for the first time. SNP 55648184 C/G and 55648186 -/T were detected more frequently in CPP group than in control group. SNP 55648176 T/G was detected less frequently in CPP group than in control group. Haplotype GGGC-ACCC was detected less frequently in CPP group. The genetic variations of KISS1 gene can be contributing factors of development of CPP. The association between the gene variations and CPP should be validated by further evidence obtained from large-scaled and functional studies.

Effectiveness and safety of pamidronate treatment in nonambulatory children with low bone mineral density.

PURPOSE: Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. METHODS: We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. RESULTS: The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. CONCLUSION: Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

Long-term tracking of glycosylated hemoglobin levels across the lifespan in type 1 diabetes: from infants to young adults.

PURPOSE: Glycosylated hemoglobin (HbA1c) is commonly used as a monitoring tool in diabetes. Due to the potential influence of insulin resistance (IR), HbA1c level may fluctuate over a person's lifetime. This study explores the long-term tracking of HbA1c level in individuals diagnosed with type 1 diabetes mellitus (T1DM) from infancy to early adulthood. METHODS: The HbA1c levels in 275 individuals (121 males, 43.8%) diagnosed with T1DM were tracked for an average of 9.4 years. The distribution of HbA1c levels was evaluated according to age with subgroups divided by gender, use of continuous glucose monitoring (CGM), and the presence of complications. RESULTS: HbA1c levels were highest at the age of 1 year and then declined until age 4, followed by a significant increase, reaching a maximum at ages 15-16 years. The levels subsequently gradually decreased until early adulthood. This pattern was observed in both sexes, but it was more pronounced in females. Additionally, HbA1c levels were higher in CGM nonusers compared with CGM users; however, regardless of CGM usage, an age-dependent pattern was observed. Furthermore, diabetic complications occurred in 26.8% of individuals, and the age-dependent pattern was observed irrespective of diabetic complications, although HbA1c levels were higher in individuals with diabetic complications. CONCLUSION: HbA1c levels vary throughout the lifespan, with higher levels during adolescence. This trend is observed regardless of sex and CGM usage, potentially due to physiological IR observed during adolescence. Hence, physiological IR should be considered when interpretating HbA1c levels during adolescence.

Effects of Early Wake-Up Time on Obesity in Adolescents.

Background: Although numerous studies have reported that obesity in adolescents is related to shorter sleep duration, few studies have reported the effect of sleep timing, particularly early wake-up time, on obesity. Objectives: To investigate the association between wake-up time and adolescent obesity. Methods: Using the Korean National Health and Nutrition Examination Survey VII data, 1301 middle school and high school students were selected and grouped according to BMI. Sleep timing and lifestyle factors were evaluated using self-reported questionnaires. Results: The mean bedtime and wake-up time were 00:09 am and 07:06 am, respectively. Despite similar bedtimes, the group with overweight/obesity woke up earlier than the group with underweight/normal weight. The BMI z-score and the overweight/obesity relative risk decreased as the wake-up time was delayed, even after adjustment for covariates. Participants who woke up before 06:50 am had a 1.82-fold higher risk of having overweight/obesity than those who woke up after 07:30 am. Participants who woke up late tended to sleep longer than those who woke up early. Conclusions: Waking up early is significantly associated with an increased BMI z-score in adolescents and may be a risk factor for overweight/obesity.

Establishment of IGF-1 and IGFBP-3 continuous reference percentiles from data of healthy children using three kinds of immunoassay systems.

Background and aims: Appropriate continuous reference intervals (RIs) for serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are important for diagnosing growth hormone deficiency or excess. Material and methods: We retrospectively reviewed serum IGF-1 and IGFBP-3 levels in Korean children aged 0-17 years who were diagnosed as healthy during a short stature workup in the outpatient clinics of three hospitals. IGF-1 and IGFBP-3 levels were measured using various immunoassays, including Liaison XL for IGF-1, an immunoradiometric assay (IRMA) for IGFBP-3 (n = 5522), and Immulite 2000 (n = 3036) and cobas e801 (n = 314). We established RIs from the 2.5th to 97.5th percentile RI curves using the lambda-mu-sigma (LMS) method for each sex group. Results: Pediatric serum continuous IGF-1 and IGFBP-3 reference percentiles by LMS method were found to be immunoassay method-dependent, but aligned relatively well with the manufacturers' RIs. IGFBP-3 levels displayed notable discrepancies among the different immunoassay methods. Conclusion: Age- and sex-specific pediatric LMS based continuous reference intervals are method dependent and they should be calculated for dynamic parameters that show variations throughout childhood.

Prediction of insulin resistance and elevated liver transaminases using serum uric acid and derived markers in children and adolescents.

OBJECTIVE: To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. RESULTS: Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. CONCLUSIONS: Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.