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.

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.

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.

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.

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.

Changes in the Prevalences of Obesity, Abdominal Obesity, and Non-Alcoholic Fatty Liver Disease among Korean Children during the COVID-19 Outbreak.

PURPOSE: We aimed to investigate the prevalences of obesity, abdominal obesity, and non-alcoholic fatty liver disease (NAFLD) among children and adolescents during the coronavirus disease 2019 (COVID-19) outbreak. MATERIALS AND METHODS: This population-based study investigated the prevalences of obesity, abdominal obesity, and NAFLD among 1428 children and adolescents between 2018-2019 and 2020. We assessed the prevalences of obesity, abdominal obesity, and NAFLD according to body mass index, age, sex, and residential district. Logistic regression analyses were performed to determine the relationships among obesity, abdominal obesity, and NAFLD. RESULTS: In the obese group, the prevalence of abdominal obesity increased from 75.55% to 92.68%, and that of NAFLD increased from 40.68% to 57.82%. In age-specific analysis, the prevalence of abdominal obesity increased from 8.25% to 14.11% among participants aged 10-12 years and from 11.70% to 19.88% among children aged 13-15 years. In residential district-specific analysis, the prevalence of both abdominal obesity and NAFLD increased from 6.96% to 15.74% in rural areas. In logistic regression analysis, the odds ratio of abdominal obesity for NAFLD was 11.82. CONCLUSION: Our results demonstrated that the prevalences of abdominal obesity and NAFLD increased among obese Korean children and adolescents and in rural areas during the COVID-19 outbreak. Additionally, the prevalence of abdominal obesity increased among young children. These findings suggest the importance of closely monitoring abdominal obesity and NAFLD among children during COVID-19, focusing particularly on obese young children and individuals in rural areas.

Comparison of the effect of gonadotropin-releasing hormone agonist dosage in girls with central precocious puberty.

PURPOSE: There are no definite guidelines on the optimal dosage of gonadotropin-releasing hormone (GnRH) agonist for treatment of central precocious puberty (CPP). We compared growth outcomes of GnRH agonist at different dosages in girls with idiopathic CPP to assess the optimal dosage. METHODS: This retrospective study included 86 girls with idiopathic CPP who had been treated with GnRH agonist for at least one year and had attained their final adult height. Leuprolide was given as fixed dosage (3.75 mg every 4 weeks in body weight >20 kg, n=72) or weight-based dosage (60-85 µg/kg every 4 weeks, n=14). We compared suppression of advanced puberty and treatment response between the 2 groups. RESULTS: Peak estradiol and luteinizing hormone and bone age (BA)/chronological age after injection of GnRH agonist were effectively suppressed in both groups. In both groups, the height standard deviation score (SDS) for BA increased after treatment. Final adult height (FAH) (fixed dosage group,160.8±4.1 cm and weight-based dosage group, 161.2±4.4 cm) was significantly higher than the initial predicted adult height (PAH) (155.5±3.3 and 156.1±3.6 cm, respectively) (both P<0.001) and similar to midparental height (159.8±3.3 and 160.6±3.7 cm, respectively). There were no differences in gain in height SDS for BA and gain in height (FAH-PAH at the start) between the 2 groups. CONCLUSION: There were no differences in treatment outcome between fixed dosage (3.75 mg/4 wk) and weight-based dosage (60-85 µg/kg/4wk) of GnRH agonist. Therefore, a fixed dosage of GnRH agonist can be used more conveniently for CPP treatment without growth oversuppression.

Effect of catch-up sleep on obesity in Korean adolescents: a nationwide cross-sectional study.

Background: Adolescents have weekday/weekend sleep discrepancies and may compensate for weekday sleep debt through sleep extension on weekends. Objective: We investigated the effects of total sleep duration on weekdays/weekends on obesity and determined if weekend catch-up sleep has an ameliorating effect on obesity in Korean adolescents. Methods: Using data from the KNHANES VII, 1,306 middle and high school students were assessed for total sleep duration on weekdays, weekends, and the entire week, as well as weekend sleep extension. Participants were classified into four groups according to weekend sleep extension. Results: Total sleep duration and weekend sleep duration were negatively associated with body mass index z-score. Increased weekend sleep duration and sleep extension on weekends decreased the relative risk of overweight/obesity with each 30 min increment, reducing the risk by a factor of 0.39 and 0.93, respectively. The risk of overweight/obesity in adolescents who slept less than 6 h on weekdays increased by a factor of 1.93 when they slept for less than 3 h on weekends. Conclusion: Weekend catch-up sleep had a negative dose-dependent association with obesity in Korean adolescents. Sleeping longer on weekends may be associated with a decreased risk of obesity, even if the adolescent obtains less sleep during weekdays. However, further prospective studies are needed to establish the causality between extended weekend sleep and obesity.

Parental metabolic syndrome and elevated liver transaminases are risk factors for offspring, even in children and adolescents with a normal body mass index.

Introduction: The parent-child correlation in metabolic syndrome (MetS) and elevated transaminases is sparsely researched. We assessed the correlation of parental MetS and elevated transaminase status with these conditions in their children. Methods: Data of 4,167 youths aged 10-18 years were analyzed in a population-based survey, and the parental characteristics were stratified by the presence or absence of MetS or alanine aminotransferase (ALT) elevation in their children. The prevalence of these conditions in children was analyzed according to their parents' status. Logistic regression analyses were performed with MetS and ALT elevation in youth as the dependent variables. Results: The proportions of MetS and ALT elevation were higher in parents of children with MetS and ALT elevation than in those without, even among youths without obesity. In logistic regression analyses, age, body mass index-standard deviation score (BMI-SDS), and ALT elevation were positively associated with MetS, whereas age, male sex, BMI-SDS, protein intake, and MetS were positively associated with ALT elevation. Higher protein intake was related to ALT elevation, whereas metabolic components and nutritional factors were closely related in parents and their children. Odds ratios (OR) of ALT elevation for MetS was 8.96 even after adjusting nutritional factors in the children. The OR was higher for ALT elevation in the children of parents with MetS and ALT elevation compared to those without. ORs for MetS and ALT elevation in the children of parents with MetS were higher than those of children of parents without MetS, even after adjusting for nutritional intake. ORs for ALT elevation were higher in the children of parents with ALT elevation than those without, even after adjusting for nutritional intake and BMI of parents as well as the nutritional intake, age, sex, and BMI-SDS of the children. Conclusion: MetS and elevated liver transaminase statuses in children were associated with those of their parents even after adjusting for nutritional factors, and the relationships were more prominent in the youth without obesity.

Neurocognitive and psychosocial profiles of children with Turner syndrome.

PURPOSE: Patients with Turner syndrome (TS) have distinct neurocognitive and psychosocial characteristics. However, few clinical studies have reported neuropsychological findings in Korean patients. This study investigated the neurocognitive and psychosocial profiles of Korean children with TS. METHODS: This retrospective cross-sectional study analyzed 20 pediatric patients (<18 years) with TS at the Department of Pediatric Endocrinology at Yonsei University Severance Children's Hospital in South Korea from January 2016 to March 2019. We selected 20 age- and sex-matched controls from among those who visited the endocrinology clinic and were confirmed to have no clinical abnormalities. All participants underwent several neuropsychological tests. RESULTS: In the Korean Wechsler Intelligence Scale for Children-IV test, the Full-Scale Intelligence Quotient of the TS group was within the normal range. The Perceptual Reasoning Index, Working Memory Index, and Processing Speed Index scores were significantly lower in the TS group than in the control group. In contrast, the Verbal Comprehension Index did not differ significantly between the groups. The Comprehensive Attention Test results showed that the TS group displayed borderline visual selective attention. The social quotient score was significantly lower in the TS group than in the control group. CONCLUSION: Pediatric patients with TS in Korea displayed distinct neurocognitive and psychosocial characteristics. Patients in the TS group maintained their verbal function, but their attention, visuospatial function, and social competence were low. Our findings will contribute to the development of education programs for patients with TS to improve their neurocognitive and psychosocial functioning.

Comparison of growth response and adverse reaction according to growth hormone dosing strategy for children with short stature: LG Growth Study.

OBJECTIVE: Growth hormone (GH) dosage in children is conventionally determined either by body weight (BW) or body surface area (BSA). However, there is no consensus on the calculation method for proper GH treatment dose. We aimed to compare growth response and adverse reactions between BW- and BSA-based GH treatment doses for children with short statures. DESIGN: Data from 2284 GH-treated children were analyzed. Distributions of BW- and BSA-based GH treatment doses and their association with growth response parameters, including changes in height, height standard deviation score (SDS), body mass index (BMI), and safety parameters, such as changes in insulin-like growth factor (IGF)-I SDS and adverse events, were investigated. RESULTS: The mean BW-based doses were close to the recommended dose's upper limit in participants with GH deficiency and idiopathic short stature, while they were below the recommended dose in patients with Turner syndrome (TS). As age and BW increased, BW-based dose decreased, whereas BSA-based dose increased. Gain in height SDS was positively associated with BW-based dose in the TS group and negatively associated with BW in all groups. Despite having a lower BW-based dose, the overweight/obese groups had a higher BSA-based dose and higher frequencies of children with high IGF-I and adverse events than those of the normal-BMI group. CONCLUSIONS: In children of older age or with high BW, BW-based doses can be overdosed in terms of BSA. and BW-based dose positively correlated with height gain only in the TS group. BSA-based doses represent an alternative dosing strategy in children who are overweight/obese.

Bone Age Estimation and Prediction of Final Adult Height Using Deep Learning.

PURPOSE: The appropriate evaluation of height and accurate estimation of bone age are crucial for proper assessment of the growth status of a child. We developed a bone age estimation program using a deep learning algorithm and established a model to predict the final adult height of Korean children. MATERIALS AND METHODS: A total of 1678 radiographs from 866 children, for which the interpretation results were consistent between two pediatric endocrinologists, were used to train and validate the deep learning model. The bone age estimation algorithm was based on the convolutional neural network of the deep learning system. The test set simulation was performed by a deep learning program and two raters using 150 radiographs and final height data for 100 adults. RESULTS: There was a statistically significant correlation between bone age interpreted by the artificial intelligence (AI) program and the reference bone age in the test set simulation (r=0.99, p<0.001). In the test set simulation, the AI program showed a mean absolute error (MAE) of 0.59 years and a root mean squared error (RMSE) of 0.55 years, compared with reference bone age, and showed similar accuracy to that of an experienced pediatric endocrinologist (rater 1). Prediction of final adult height by the AI program showed an MAE of 4.62 cm, compared with the actual final adult height. CONCLUSION: We developed a bone age estimation program based on a deep learning algorithm. The AI-derived program demonstrated high accuracy in estimating bone age and predicting the final adult height of Korean children and adolescents.

Effects of Androgen Treatment on Growth in Patients with 5-α-Reductase Type 2 Deficiency.

BACKGROUND: Patients with 5-α-reductase type 2 deficiency (5αRD2) require androgen treatment for the growth of normal male external genitalia. Since limited research has been conducted on the effects of androgen treatment on height in individuals with 5αRD2, we investigated the effect of androgen treatment on bone age (BA) and the height status in children with 5αRD2. METHODS: Of the 19 participants who were followed up for an average of 10.6 years, 12 received androgen treatment. BA and height standard deviation scores (SDS) were compared between the treatment and non-treatment groups, as well as between the dihydrotestosterone (DHT) and testosterone enanthate (TE) treatment groups. RESULTS: Despite the above-average height of the 19 patients with 5αRD2, the height SDS relative to BA (htSDS-BA) was below average, particularly in the androgen treatment group. DHT treatment did not lead to an increase in BA or htSDS-BA, whereas TE treatment resulted in BA advancement and decreased htSDS-BA, especially in the prepubertal period. CONCLUSIONS: DHT treatment is more favorable for height than TE treatment in patients with 5αRD2, particularly during the prepubertal period. Therefore, age and the type of androgen used should be carefully considered to minimize the risk of height reduction in these patient groups.

Insulin Requirement and Complications Associated With Serum C-Peptide Decline in Patients With Type 1 Diabetes Mellitus During 15 Years After Diagnosis.

Objective: C-peptide is conventionally used in assessing pancreatic function in patients with diabetes mellitus. The clinical significance of this molecule during the course of type 1 diabetes mellitus (T1DM) has been recently revisited. This study aimed to investigate the natural course of C-peptide in T1DM patients over the period of 15 years and analyze the association between the residual C-peptide and diabetes complications. Methods: This retrospective study included a total of 234 children and adolescents with T1DM. Patient data including sex, age at diagnosis, anthropometric measures, daily insulin dose, serum HbA1c, post-prandial serum C-peptide levels, lipid profiles, and diabetic complications at the time of diagnosis and 1, 3, 5, 10, and 15 years after diagnosis were retrospectively collected. Results: Among the 234 patients, 101 were men and 133 were women, and the mean patient age at initial diagnosis was 8.3 years. Serum C-peptide decreased constantly since the initial diagnosis, and showed a significant decline at 3 years after diagnosis. At 15 years after diagnosis, only 26.2% of patients had detectable serum C-peptide levels. The subgroup with older patients and patients with higher BMI standard deviation score showed higher mean serum C-peptide, but the group-by-time results were not significant, respectively. Patients with higher serum C-peptide required lower doses of insulin and had fewer events of diabetic ketoacidosis. Conclusion: Serum C-peptide decreased consistently since diagnosis of T1DM, showing a significant decline after 3 years. Patients with residual C-peptide required a lower dose of insulin and had a lower risk for diabetic ketoacidosis.

Association of hypercalciuria with vitamin D supplementation in patients undergoing ketogenic dietary therapy.

Background: Ketogenic dietary therapy (KDT) is used as an effective treatment for epilepsy. However, KDT carries the risk of bone health deterioration; therefore, vitamin D supplementation is required. Vitamin D replacement therapy in KDT has not been established because it may be related to hypercalciuria/urolithiasis, which are common adverse effects of KDT. Hence, this study aimed to evaluate the dose-dependent association between vitamin D3 and hypercalciuria/urolithiasis in patients undergoing KDT and dose optimization for renal complications. Materials and methods: Overall, 140 patients with intractable childhood epilepsy started 3:1 KDT (lipid to non-lipid ratio) at the Severance Children's Hospital from January 2016 to December 2019. Regular visits were recommended after KDT initiation. Participants were assessed for height, weight, serum 25-hydroxyvitamin D (25-OH-D3) level, parathyroid hormone level, and ratio of urinary excretion of calcium and creatinine (Uca/Ucr). Kidney sonography was conducted annually. Patients who already had urolithiasis and were taking hydrochlorothiazide before KDT, failed to maintain KDT for 3 months, did not visit the pediatric endocrine department regularly, did not take prescribed calcium and vitamin D3 properly, or needed hospitalization for > 1°month because of serious medical illness were excluded. Data from patients who started diuretic agents, e.g., hydrochlorothiazide, were excluded from that point because the excretion of calcium in the urine may be altered in these patients. Result: In total, 49 patients were included in this study. Uca/Ucr ratio significantly decreased with increasing levels of 25-OH-D3 (p = 0.027). The odds ratio for hypercalciuria was 0.945 (95% confidence interval, 0.912-0.979; p = 0.002) per 1.0 ng/mL increment in 25-OH-D3 level. Based on findings of receiver operating characteristic curve analysis and Youden's J statistic, the cut-off 25-OH-D3 level for preventing hypercalciuria was > 39.1 ng/mL at 6 months. Furthermore, the vitamin D3 supplementation dose cut-off was > 49.5 IU/kg for hypercalciuria prevention. Conclusion: An inverse relationship between Uca/Ucr ratio and 25-OH-D3 level was noted, which means that vitamin D supplementation is helpful for preventing hypercalciuria related to KDT. We suggest that the recommended 25-OH-D3 level is > 40 ng/mL for hypercalciuria prevention and that KDT for children with epilepsy can be optimized by vitamin D3 supplementation at 50 IU/kg.

Comparison of the Modified TyG Indices and Other Parameters to Predict Non-Alcoholic Fatty Liver Disease in Youth.

We investigated the modified triglycerides-glucose (TyG) indices and other markers for non-alcoholic fatty liver disease (NAFLD) in 225 participants aged 10-19 years, and the participants were divided into subgroups according to their NAFLD grade. We performed logistic regression analysis and calculated the odds ratios (ORs) with 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter, with those of tertile 1 as a reference. The area under the receiver operating characteristic (ROC) curve was calculated to compare the parameters for identifying NAFLD. TyG and modified indices, aspartate transaminase-to-platelet ratio index (APRI)-body mass index (BMI), APRI-BMI standard deviation score (SDS), APRI waist-to-hip ratio, fibrosis-4 index (FIB)-4, and hepatic steatosis index (HSI) were higher in participants with NAFLD than in those without NAFLD. The ORs and 95% CIs for NAFLD progressively increased across tertiles of each parameter. TyG and modified TyG indices, FIB-4, HSI, and modified APRIs, except APRI waist-to-height ratio, predicted NAFLD significantly through ROC curves. Modified TyG indices, APRI-BMI SDS, and HSI were superior to the other markers for NAFLD prediction. Modified TyG indices, APRI-BMI SDS, and HSI appear to be useful for assessing NAFLD in youths.

Trends in Prediabetes and Non-Alcoholic Fatty Liver Disease Associated with Abdominal Obesity among Korean Children and Adolescents: Based on the Korea National Health and Nutrition Examination Survey between 2009 and 2018.

Investigations on the trends of prediabetes and non-alcoholic fatty liver disease (NAFLD) among children are scarce. We aimed to analyze the trends of prediabetes and NAFLD, as well as their association, among Korean children and adolescents from 2009 to 2018. This study investigated the prevalence of prediabetes, NAFLD, and abdominal obesity among 6327 children and adolescents aged 10-18 years according to age, sex, and body mass index (BMI) using a nationally representative survey. The prevalence of prediabetes, NAFLD, and abdominal obesity increased from 5.14%, 8.17%, and 5.97% respectively, in 2009 to 10.46%, 12.05%, and 10.51% respectively, in 2018. In age-specific analyses, an adverse trend in NAFLD was significant only in participants aged 16-18 years while the prevalence of prediabetes worsened significantly in all age groups. In BMI-specific analyses, the prevalence of prediabetes and NAFLD increased significantly only in participants with normal BMI. In logistic regression analysis, the odds ratio of prediabetes for NAFLD was 1.85 and those of abdominal obesity for prediabetes and NAFLD was 1.85 and 9.34, respectively. Our results demonstrated that the prevalence of prediabetes and NAFLD was increasing in association with abdominal obesity in Korean children and adolescents.