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Monogenic diabetes mellitus, which is diabetes caused by a defect in a single gene that is associated with β cell function or insulin action, accounts for 1% to 6% of all pediatric diabetes cases. Accurate diagnosis is important, as the effective treatment differs according to genetic etiology in some types of monogenic diabetes: high-dose sulfonylurea treatment in neonatal diabetes caused by activating mutations in KCNJ11 or ABCC8; low-dose sulfonylurea treatment in HNF1A/HNF4A-diabetes; and no treatment in GCK diabetes. Monogenic diabetes should be suspected by clinicians for certain combinations of clinical features and laboratory results, and approximately 80% of monogenic diabetes cases are misdiagnosed as type 1 diabetes or type 2 diabetes. Here, we outline the types of monogenic diabetes and the clinical implications of genetic diagnosis.

Background: Pediatric obesity has increased over the decades, and in particular, severe pediatric obesity has become a serious public health problem. A concern has arisen that the COVID-19 pandemic may exacerbate the incidence of childhood obesity.Current Concepts: The consequences of severe pediatric obesity are more devastating than those of moderate obesity. Children with severe obesity are at a greater risk for hypertension, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, atherosclerosis, and adult obesity. Correct assessment and diagnosis of a child with severe obesity is key to successful therapy. A thorough history and physical examination are important in identifying monogenic obesity or metabolic syndrome. Eating behaviors and psychosocial factors should be assessed to improve weight management outcomes. Treatment options for severe pediatric obesity include lifestyle modification, pharmacotherapy, and metabolic and bariatric surgery. Even though progress has been made with regard to the treatment of obesity, safe and effective treatment of severe pediatric obesity is challenging.Discussion and Conclusion: More efforts and innovations are needed to find a solution for the huge medical and emotional burden the children with severe obesity and their families are enduring.

Growth hormone (GH) treatment preference and adherence are affected by delivery device convenience, injection-site pain, confidence in correct dose administration, and device satisfaction. This survey investigated if switching device to NordiFlex® improved treatment experience in pediatric patients in South Korea.Patients aged 4-≤18 years were surveyed. Participants were NordiFlex® users who previously used NordiLet®/other devices. Participants compared preference, self-reported adherence, satisfaction, perceived ease of use, and device subjective benefits (across four domains:Ninety-four patients were enrolled, of which 91.5% previously used NordiLet®. Significantly more patients preferred, and were more satisfied with NordiFlex® vs. previous device; mean score: 0.65 (95% confidence interval [CI]:0.41;0.88) and 0.61 (95% CI:0.36;0.85), respectively. Participants reported greater perceived ease of use (0.49 [95% CI:0.26;0.72]) and fewer missed injections (0.20 [95% CI:0.06;0.34], with NordiFlex® vs. previous device. Bivariate analysis showed significant associations between preference for NordiFlex® and higher scores onThese results suggest that improvements in device features could be associated with improved treatment experience.

Purpose Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis and occurs in children between 10 to 18 years old, during periods of growth spurts and puberty changes. In patients with central precocious puberty (CPP), due to early growth spurt, AIS is expected to develop before 10 years of age. Both AIS and CPP are more common in girls than in boys. The aim of this study was to determine the prevalence of AIS in girls with CPP and to evaluate the effect of treatment with gonadotropin-releasing hormone (GnRH) agonists on progression of scoliosis in these patients. Methods We retrospectively reviewed medical records of 553 girls, 338 with CPP and 215 without CPP. Scoliosis angle was measured on the standing frontal radiograph of each patient according to the Cobb method. Patients with a Cobb angle of 10° or more were diagnosed with scoliosis. For girls with CPP, followup spine radiographs were collected 1 year after treatment with GnRH agonists. Progression of scoliosis before and after treatment was compared in terms of Cobb angle changes. Results AIS was more prevalent in girls that were affected by CPP compared to controls without CPP (11.5% vs. 6.0%, CPP girls vs. non-CPP girls, respectively, P=0.031). The peak serum luteinizing hormone level positively correlated with Cobb angle (R2=0.015, P=0.023) in the CPP group. No progression of scoliosis was observed in CPP girls after one year of GnRH agonist treatment. Additionally, the prevalence of scoliosis decreased in CPP girls after 1 year of the treatment. Conclusion We report that the prevalence of AIS is higher in girls with CPP than in non-CPP patients. A regular follow-up schedule for spine radiographs should be considered to reduce the risk of progression. Furthermore, GnRH agonist treatment for CPP may have a suppressive effect on progression of AIS.

Ji-Eun Lee,1 Se Young Kim,2 Jae-Ho Yoo,3 Il Tae Hwang,4 Jung Sub Lim,5 Kyung Hee Yi,6 Young-Jun Rhie,7 Gyung Min Lee,8 Hyo-Kyoung Nam,9 Hyun Wook Chae,10 Eun Young Kim,11 Chong Kun Cheon,12 Jieun Lee,13 Young Suk Shim,14 YuJin Lee,15 Eun Young Kim,15 Jin Soon Hwang16 1Department of Pediatrics, Inha University Hospital, Inha University Graduate School of Medicine, Incheon, Republic of Korea; 2Department of Pediatrics & Adolescent Medicine, Bundang Jeseang General Hospital, Daejin Medical Center, Seongnam, Republic of Korea; 3Department of Pediatrics, Dong-a University Hospital, Dong-a University College of Medicine, Busan, Republic of Korea; 4Department of Pediatrics, Kangdong Sacred Heart Hospital, Hallym University, College of Medicine, Seoul, Republic of Korea; 5Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Republic of Korea; 6Department of Pediatrics, Wonkwang University Sanbon Medical Center, Gunpo, Republic of Korea; 7Department of Pediatrics, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Republic of Korea; 8Department of Pediatrics, Konyang University Hospital, Daejeon, Republic of Korea; 9Department of Pediatrics, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea; 10Department of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 11Department of Pediatrics, Chosun University Hospital, Chosun University School of Medicine, Gwangju, Republic of Korea; 12Department of Pediatrics, Pusan National University Children’s Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea; 13Department of Pediatrics, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea; 14Department of Pediatrics & Adolescent Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Republic of Korea; 15Life Sciences, LG Chem, Ltd., Seoul, Republic of Korea; 16Department of Pediatrics & Adolescent Medicine, Ajou University Hospital, Ajou University School of Medicine, Suwon, Republic of KoreaCorrespondence: Jin Soon HwangDepartment of Pediatrics & Adolescent Medicine, Ajou University Hospital, Ajou University School of Medicine, 164, World cup-ro, Yeongtong-gu, Suwon-si, Gyeonggi-do 16499, Republic of KoreaTel +82 31 219 5166Fax +82 31 219 5169Email pedhwang@ajou.ac.krPurpose: To assess the usability and safety of the disposable pen compared to those of reusable devices in patients receiving recombinant human growth hormone (rhGH) treatment.Patients and methods: This study was a multicenter, single-arm, open-label, switch-over, prospective, Phase IV trial. After screening, eligible patients who were previously treated with rhGH using a reusable device were enrolled to receive treatment with the disposable pen for 8 weeks. The ease of use, preference, and tolerability of the disposable pen compared to those of the reusable device were assessed by the subjects and/or their caregivers using a questionnaire. Adverse events were evaluated by the investigators.Results: Of 116 subjects enrolled in this study, 115 received treatment with the disposable pen and 109 completed the study. The mean age of the subjects was 9.4 years. Compared to the previous reusable device, the disposable pen was assessed as significantly easier to use (mean value 7.88, 95% confidence interval (CI) [7.45–8.30] on a numerical scale ranging from 0 (far less easy) to 10 (far easier)). Furthermore, the percentage of subjects who preferred the disposable pen to the previously used reusable device was 75.7% (95% CI [67.6%–83.8%]). The percentages of subjects who rated pain and discomfort at the injection site as “not at all” were higher after using the disposable pen compared to the reusable device. No specific safety concerns were identified.Conclusion: The disposable pen is easier to use than the reusable devices and is preferred by approximately 75% of patients receiving rhGH treatment. Moreover, the disposable pen is safe and acceptable. Therefore, it could be a good alternative to reusable devices. The disposable pen is expected to provide benefits to patients receiving rhGH treatment.Clinicaltrials.gov identifier: NCT03015909.Keywords: growth hormone, disposable equipment, patient preference, usability, safety

Purpose Obesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration. Methods This was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, Pl0.001). Results Serum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, Pl0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, Pl0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, Pl0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration. Conclusion Hyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.

Purpose Bone plays a role in glucose metabolism through the release of uncarboxylated osteocalcin into the systemic circulation. The identified novel roles for osteocalcin include increasing insulin secretion and sensitivity, energy expenditure, reduction of fat mass, and mitochondrial proliferation and functional enhancement. This study aimed to determine serum osteocalcin levels in overweight children and to investigate the relationships of osteocalcin with glucose metabolism and insulin sensitivity. Methods After overnight fasting, serum osteocalcin levels were measured in overweight (n=50) children between 6.0 and 12.9 years of age and nonoverweight controls (n=60). Height, weight, fasting serum glucose, insulin, alkaline phosphatase, total cholesterol, and 25 hydroxy vitamin D3 (25(OH)VitD3) were also measured in all subjects. Results There were significant differences in serum osteocalcin levels between the overweight and control groups (64.00±20.44 vs. 89.56±28.63, Pl0.001). Serum osteocalcin levels were inversely correlated with body mass index (BMI) (r=-0.283, P=0.003), weight standard deviation score (SDS) (r=-0.222, P=0.020), BMI SDS (r=-0.297, P=0.002), insulin (r=-0.313, P=0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) index (r=-0.268, P=0.005). In the subsequent multiple regression analyses, BMI, HOMA-IR, and age were determined to be independent predicting factors for serum osteocalcin. Conclusion Our findings showed associations of serum osteocalcin with glucose metabolism and insulin sensitivity in overweight children, but we could not establish a causal relationship.

Background Triptorelin depot is largely used to treat central precocious puberty (CPP) in children, and a 3-month depot has been introduced. However, data about the 3-month gonadotropin-releasing hormone use for treatment of CPP in Korean girls are not available. This study was conducted to compare the efficacy of a triptorelin 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of CPP. Methods A retrospective study, including 106 girls with CPP treated with triptorelin, was conducted. Fifty patients were treated with a triptorelin 3-month depot, and 56 were treated with a triptorelin 1-month depot. Serum luteinizing hormone (LH), follicle-stimulating hormone, and estradiol levels were analysed every 6 months after the visit. The height and bone age of each patient was evaluated at the beginning of treatment, after 6 months, and one year after therapy. Results The baseline characteristics of the girls treated with a 3-month depot were similar to those of the girls treated with a 1-month depot. A suppressed levels of LH to the triptorelin injection (serum LH < 2.5 IU/L) at 6 months was seen in 90.0% and 98.2% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.160). After 1 year of treatment, a suppressed levels of LH was seen in 93.5% and 100% of the girls treated with the 3-month and 1-month depots, respectively (P = 0.226). Height velocity showed no significant difference between the two groups. Degree of bone age advancement decreased from 1.22 ± 0.07 and 1.22 ± 0.08 years at baseline (P = 0.914) to 1.16 ± 0.07 and 1.17 ± 0.08 in the girls treated with the 3-month and 1-month depots after 1 year, respectively (P = 0.481). Conclusion This study showed that the efficacy of long-acting triptorelin 3-month was comparable to 1-month depot regarding hormonal suppression and inhibition of bone maturation. The triptorelin 11.25 mg 3-month depot is an effective treatment for girls with CPP., Graphical Abstract

Puberty is the transitional period from childhood to adult that leads to growth spurt, sexual maturation and attainment of reproductive capacity. Precocious puberty is defined when secondary sexual characteristics develop before the age of eight for girls and nine for boys. Central precocious puberty (CPP) is diagnosed when the process is driven by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Many factors promote CPP, and the thyroid function is thought to be one of them. In our previous study, thyroid stimulating hormone (TSH) was higher in the CPP group than that of the participants without CPP. This elevation of TSH in CPP is said to be associated with pubertal luteinizing hormone (LH) elevation. The aim of this study was to evaluate the causal relationship between TSH and LH in CPP patients. A total of 221 girls diagnosed with CPP and treated with GnRH agonists were included. All participants except one showed LH suppression (peak LH < 3 IU/L), and serum levels of follicle stimulating hormone (FSH) were also lower after the treatment. These results indicate that puberty has slowed down and that the patients were successfully treated for CPP. As for thyroid hormones, TSH was significantly lower and free thyroxine (fT4) levels were higher after 12 months of GnRH agonist treatment compared with baseline. With GnRH agonist treatment, the serum levels of LH and TSH were decreased, suggesting that the increase in serum TSH levels is associated with premature LH elevation in girls with CPP.

Objectives: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, which occurs usually in the periods of growth spurts and puberty changes. The spinal curve progression in AIS is related to growth, skeletal maturity and sexual maturity. Growth hormone treatment has been used to improve final adult height by increasing growth velocity in children with short stature. Therefore, AIS is expected to occur more frequently in children treated with growth hormone. The aim of this study was to investigate the relationship between AIS and growth hormone treatment in short children. Methods: A total 115 subjects aged 2.1 to 16.9 years who had been treated with growth hormone because of growth hormone deficiency (n=83), idiopathic short stature (n=16) and small for gestational age (n=16) were included. Their medical records were reviewed retrospectively. The scoliosis angle of each subject was measured on the standing frontal radiograph according to the Cobb method. A curve with a Cobb angle of 10 degrees or more is defined scoliosis. Follow up Cobb angle were measured after 1-year of growth hormone treatment. Results: Cobb angle has been increased after 1-year growth hormone treatment (6.1±3.1 vs. 6.9±3.4, P=0.024). The change of Cobb angle was correlated with serum insulin like growth factor-1 level at baseline (r=0.274, P=0.003) and after 1-year of growth hormone treatment (r=0.220, P=0.020). There was no significant correlation between the change of Cobb angle and growth velocity. The prevalence of AIS has been increased after 1-yrear of growth hormone treatment (11.3% vs. 19.1%, P=0.009). Conclusion: Growth hormone treatment in children with short stature seems to be associated with occurring and worsening of AIS.

Purpose Regarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings. Methods A total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes. Results As of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5-11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78). Conclusions This registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment.

Purpose Low vitamin D level is common in adults with diabetes mellitus (DM). We assessed vitamin D level and its associated factors in Korean youth with type 1 DM. Methods Type 1 DM cases (n=85) and healthy controls (n=518) aged

Osteocalcin is the non-collagenous protein produced by osteoblasts in bone. When it is released into systemic circulation in its uncarboxylated form, it regulates fat and glucose metabolism. Recent studies have shown that osteocalcin is also involved in male fertility. Because the onset of puberty is determined by ethnic, genetic, environmental, and metabolic factors, we focused on determining the role of osteocalcin in the onset of puberty. Central precocious puberty (CPP) is defined as the activation of the hypothalamic-pituitary-gonadal axis before the age of 8 in girls and 9 in boys. CPP is diagnosed when peak luteinizing hormone (LH) reaches ≥ 5.0 IU/l after stimulation with gonadotropin-releasing hormone (GnRH). This retrospective study included 206 girls who showed breast budding before the age of 8 and whose bone age was more advanced than their chronological age. The CPP group included 100 girls who were diagnosed with CPP, and 106 girls were the non-CPP group whose peak LH did not reach ≥ 5.0 IU/l after GnRH stimulation test. Serum osteocalcin levels were measured to investigate the relationship between osteocalcin and the onset of puberty. Our data showed that serum osteocalcin levels were significantly higher in the CPP group (87.7 ± 24.4 ng/ml vs. 68.3 ± 19.5 ng/ml, P < 0.001). The multivariate analysis revealed that an increase in bone age and peak LH was significantly associated with the serum osteocalcin level. The results of this study suggest that serum osteocalcin is associated with the onset of puberty in girls.

Background: This study aimed to investigate the relationship between daily sitting time and the risk of metabolic syndrome in Korean adolescents. Methods: Data from 486 adolescents aged 12–18 years were obtained from national surveys. Daily sitting time was measured using questionnaires and divided into three intervals: Results: The mean daily sitting time and prevalence of positive metabolic components were 620.9±9.9 min/day and 45.5±2.7%, respectively. In a multivariate logistic regression analysis, adolescents who sat longer were more likely to have metabolic components (p Conclusions: Longer daily sitting time appears to be associated with an increased risk of metabolic syndrome in adolescents. These findings highlight the need to focus on reducing sitting time for all adolescents, not just for those at risk of obesity.

Background : Serum fibroblast growth factor 21 (FGF21) has been suggested to be a possible biomarker for early detection of metabolic syndrome and type 2 diabetes in adults. However, few studies have investigated the correlation between FGF21 levels and metabolic parameters in children. This study sought to evaluate the relationship between FGF21 and metabolic parameters in obese Korean children and adolescents. Methods : Fasting serum FGF21 and adiponectin levels as well as fasting insulin, glucose, transaminases, and lipid profiles were measured by enzyme-linked immunosorbent assays in 45 lean and 70 obese children aged 7–14 years. Independent t-test and multivariate correlation analysis were used to evaluate the relationship between FGF21 and metabolic parameters. Results : Serum FGF21 was significantly higher in obese children than in lean children. Serum FGF21 levels were positively correlated with insulin resistance index homeostasis model assessment (HOMA-IR) (r=0.355, P=0.004) and triglycerides (r=0.423, P

Idiopathic short stature (ISS) is a heterogeneous group and their responsiveness to growth hormone treatment varies among individuals. The aim of this study was to identify homogeneous phenotypes to better assess response before the initiation of treatment. We focused on person-centered approaches using a latent profile analysis. Clinical data of 218 children (127 boys and 91 girls) aged 4-15 years were obtained from the "LG Growth Study" which is a non-interventional Korean multicenter registry for growth hormone treatment. Growth hormone dose, first-year difference in height standard deviation score (Δheight SDS), mid-parental height SDS, and initial bone age were inputted into the model. The distribution of scatter plot was clearly distinguished at the chronological age of 8.83 years, Δheight SDS of 0.82 and mean GH dose of 0.36 mg/kg/week. The latent profile analysis revealed three distinct phenotypes names as follows: younger good responder (n = 56), older good responder (n = 111), and older poor responder (n = 51) groups. Despite more than twice the mean growth hormone dose, the older poor responder group showed the least improvement in the mean Δheight SDS. The pretreatment height velocity and peak growth hormone level were lower for the older poor responder group compared with those of the older good responder group. The statistically optimal cutoff point for predicting poor response was 3.41 cm/year for pretreatment height velocity and 9.18 ng/mL for peak growth hormone level. This study offers a new multidimensional approach to enable personalized growth hormone treatment optimization according to ISS phenotypes.

Background Vitamin D metabolism has been associated with type 1 diabetes. Objective We aimed to clarify the association of 25-hydroxylase (CYP2R1) and 1α-hydroxylase (CYP27B1) with risk of developing type 1 diabetes in Korean children. Methods In total, 252 children (96 type 1 diabetes and 156 healthy controls) under the age of 20 years were recruited. Serum 25-hydroxyvitamin D (25OHD) and 1α,25-dihydroxyvitamin D [1α,25(OH)2 D] levels were determined. Allelic, genotypic, and haplotypic distribution of CYP2R1 (rs12794714, rs10766196, rs10741657, rs2060793, and rs10766197) and CYP27B1 (rs4646536, rs10877012, and rs3782130) polymorphisms were determined. Clinical and biochemical data were analyzed according to genotype. Results Mean vitamin D level was considerably lower, and vitamin D deficiency was more prevalent in children with type 1 diabetes than in healthy controls. The GG genotype of CYP2R1 rs12794714 and AA genotype of CYP2R1 rs10766196 were significantly associated with risk of developing type 1 diabetes (odds ratio 2.00, 95% confidence interval 1.176-3.413 and odds ratio 1.88, 95% confidence interval 1.103-3.195, respectively). The GG+GA genotype of CYP2R1 rs12794714 and AA+AG genotype of CYP2R1 rs10766196 were associated with prevalent vitamin D deficiency in children with type 1 diabetes. These genotypes did not differ with respect to glycosylated hemoglobin and daily insulin requirement. Conclusions Serum 25OHD and 1α,25(OH)2 D levels were lower in children with type 1 diabetes than in healthy controls. CYP2R1 rs12794714 and rs10766196 polymorphisms were associated with a higher risk of type 1 diabetes. Thus, polymorphisms in vitamin D metabolism may contribute to susceptibility to type 1 diabetes in Korean children.

PurposeThe aim of this registry study was to analyze the long-term safety and effectiveness of recombinant human growth hormone (rhGH) in South Korean pediatric patients (≥2 years of age) with growth hormone deficiency GHD) of idiopathic or organic etiology, idiopathic short stature, Turner syndrome, small for gestational age and chronic renal failure.MethodsThe study patients were followed-up till two years after the epiphyseal closure, with visits scheduled every six months. The outcome measures included the incidence of adverse events (AEs, in particular, neoplasia, glucose intolerance and hypothyroidism), as well as height standard deviation score (Ht SDS) and annual height velocity. The results of the interim analysis of a 5-year accumulated data for 2,024 patients (7,342 patient-years, PY) are presented.ResultsA total of 14 neoplasms were diagnosed (191/100,000 PY); 7 out of 9 malignancies were recurrent craniopharyngioma found in patients with organic GHD. Seven cases of glucose intolerance (95/100,000 PY) and 22 cases of hypothyroidism (300/100,000 PY) were detected; about half of the cases (4 and 10 cases each) were considered to be related with rhGH treatment. Most of the growth-retarded patients showed continuous improvement in Ht SDS, with the most prominent effect observed within a year of treatment initiation. The beneficial effect of rhGH on Ht SDS gain was maintained for 2-4 years.ConclusionsThe incidence of AEs of interest in rhGH-treated patients was low, and most of the neoplasms were benign and/or non-related to rhGH. Most patients benefited from the therapy in terms of height increment.

Background Oral glucose tolerance test (OGTT) is a traditional diagnostic tool for diabetes. Hemoglobin A1c (HbA1c) is an alternative method used in adults; however, its application in youths has been controversial. We evaluated the diagnostic performance of HbA1c and determined optimal cutoff points for detecting prediabetes and diabetes in youth. Methods This retrospective study included 389 obese children (217 boys, 55.8%) who had undergone simultaneous OGTT and HbA1c testing at six hospitals, Korea, between 2010 and 2016. Subjects were diagnosed with diabetes (fasting glucose ≥ 7.0 mmol/L; 2-hour glucose ≥ 11.1 mmol/L) or prediabetes (fasting glucose 5.6–6.9 mmol/L; 2-hour glucose 7.8–11.0 mmol/L). The diagnostic performance of HbA1c for prediabetes and diabetes was determined using the area under the receiver operating characteristic curve (AUC). Results At diagnosis, 197 (50.6%) subjects had normoglycemia, 121 (31.1%) had prediabetes, and 71 (18.3%) had diabetes. The kappa coefficient for agreement between OGTT and HbA1c was 0.464. The optimal HbA1c cutoff points were 5.8% (AUC, 0.795; a sensitivity of 64.1% and a specificity of 83.8%) for prediabetes and 6.2% (AUC, 0.972; a sensitivity of 91.5% and a specificity of 93.7%) for diabetes. When HbA1c (≥ 6.2%) and 2-hour glucose level were used to diagnose diabetes, 100% were detected. Conclusion Pediatric criteria for HbA1c remain unclear, therefore, we recommend the combination of fasting and 2-hour glucose levels, in addition to HbA1c, in the diagnosis of childhood prediabetes and diabetes., Graphical Abstract

Purpose. In this study, we investigated the status of thyroid function and its association with metabolic risk factors in Korean adolescents. Methods. Among 2679 subjects aged 10–19 years who participated in the Korea National Health and Nutrition Examination Survey VI (2013–2015), 1067 adolescents (M=559, F=508) with available data on free T4 (FT4) and thyroid-stimulating hormone (TSH) were included. Study participants were classified into normal weight [body mass index (BMI) below 85th percentile, 80.7%], overweight (85th ≤ BMIResults. With increasing levels of BMI category, the means of TSH increased (2.73 ± 0.06, 2.77 ± 0.02, and 3.24 ± 0.22 mIU/L, P=0.031) and FT4 decreased (1.30 ± 0.01, 1.26 ± 0.02, and 1.25 ± 0.02 ng/mL, P=0.001). Positive linear associations were observed between TSH and BMI z-score (P=0.031), waist circumference (P=0.013), waist-height ratio (P=0.002), systolic blood pressure (P=0.001), total cholesterol (P=0.008), and triglyceride (P=0.002) after adjusting for age and sex. With per-unit increase in TSH, the odds ratios of having abdominal obesity (OR = 1.18, 95% CI, 1.01–1.38) and triglyceride ≥ 150 mg/dL (OR = 1.18, 95% CI, 1.04–1.34) were significantly increased after adjusting for age, sex, and BMI. Conclusions. In adolescents with obesity, TSH was higher and FT4 was lower than in adolescents with normal weight. Hyperthyrotropinemia was associated with abnormal metabolic risk factors including abdominal obesity and elevated triglyceride.

Purpose Small for gestational age (SGA) is confusingly defined as birth weight (BW) either below 3rd percentile or 10th percentile for infants. This study aimed to compare postnatal catch-up growth between SGA groups according to different definitions. Methods Data of 129 infants born with BW below the 10th percentile and admitted to Korea University Anam Hospital and Ansan Hospital were retrospectively reviewed. Height and weight were measured at 6, 12, and 24 months. Results were compared between group A (BW

Purpose This study investigated the influence of obesity on the clinical course and effect of gonadotropin-releasing hormone analog (GnRHa) treatment in girls with central precocious puberty (CPP). Methods Medical records of 182 girls with CPP treated with GnRHa were reviewed. They were divided into 2 groups: normal weight (n=108) and overweight/obesity (n=74). Chronological age (CA), bone age (BA), difference between BA and CA (BA–CA), standard deviation score (SDS) of height, body mass index (BMI), predicted adult height (PAH), and laboratory findings were compared at baseline, after 1 year, and at the end of GnRHa treatment in both groups. Results Mean BMI SDS at baseline was 0.08±0.60 in the normal weight group and 1.55±0.36 in the overweight/obesity group. Initial CA, BA, midparental height, and PAH were similar between the 2 groups. BA–CA after treatment was significantly decreased compared to baseline in both groups (P

Purpose Gonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa. Methods In this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP. Results Mean chronological and bone age at menarche were 11.9±0.7 and 12.8±0.4 years, respectively. The period between menarche and the end of treatment was 14.0±5.6 months. Posttreatment near adult height was 163.8±4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7±4.1 cm). Conclusion GnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

Purpose This study investigates the behavioral and emotional characteristics of Korean children and adolescents with type 1 diabetes mellitus (T1DM) as compared to healthy controls, and examines whether their psychological status is associated with glycemic control, insulin regimens, or disease duration. Methods A total of 37 Korean children and adolescents with T1DM, aged 6-17 years, and 38 sex- and age-matched healthy controls were included in this study. Psychological distress was assessed using the Korean child behavior checklist (K-CBCL) and children's depression inventory (CDI) after the subjects and their parents were interviewed. Results The CDI and K-CBCL scores were significantly higher in T1DM subjects compared to normal controls. The T1DM subjects with "poorly controlled" blood glucose (glycosylated hemoglobin ≥8%) and "old patients" (disease duration ≥1 year) had a tendency to show higher CDI and K-CBCL scores. There were no significant differences in CDI and K-CBCL scores between the intensive and conventional insulin therapy groups. Conclusion Children and adolescents with T1DM seem to have inferior psychological adjustment to their normal counterparts, which might be associated with glycemic control and disease duration. Psychological evaluation and intervention should be considered in the management of T1DM in children and adolescents.

Background The objective of our study was to understand the epidemiological and clinical features of respiratory adenoviral infections among children at a single institution over the course of several years. Methods From January 2005 to April 2009, 1836 children (≤15 years old) who had been admitted to Korea University Ansan Hospital were tested for acute respiratory infection. The patients who were positive for an adenovirus infection were enrolled in this study, and their medical records were retrospectively reviewed. Results Adenoviruses were isolated from 310 patients. The male to female ratio was 1.6:1 and mean age was 32 ± 24 months. Children under 5 years of age had the highest prevalence. In 2007, adenovirus infections occurred endemically throughout the year. The clinical diagnoses were primarily upper respiratory tract infections (45.4%), lower respiratory tract infections (48.1%), and neurologic disease (5.2%). Associated symptoms, signs and laboratory findings included fever (91.9%), cough (83.9%), pharyngeal injection (62.3%), rale (32.6%) and elevated C-reactive protein (93.9%). The most common radiologic findings were perihilar and peribronchial infiltrates (42.6%). Co-infections were observed in 29 cases. The mean durations of hospitalization and fever were 6.2 ± 6.5 and 4.8 ± 3.1 days, respectively. The lengths of hospitalization were similar for patients admitted for upper respiratory tract infections with severe morbidity and those admitted for lower respiratory tract infections. No children in the study died. Conclusion Our study demonstrates that respiratory adenovirus infections are an important cause of hospitalization in young children, and contribute to a significant morbidity.

Few studies have investigated the long-term effects of gonadotropin-releasing hormone (GnRH) agonist treatment on the reproductive function of central precocious puberty (CPP) girls. In this cross-sectional study, we assessed the ovarian function by analyzing the serum anti-Müllerian hormone (AMH) levels of CPP girls. Our study included 505 CPP girls subdivided into 5 groups according to the GnRH agonist treatment stage: group A (before treatment, n = 98), group B (3 months after initiation, n = 103), group C (12 months after initiation, n = 101), group D (24 months after initiation, n = 101), and group E (6 months after discontinuation, n = 102). We compared the serum AMH levels of the CPP girls with those of 100 bone age-matched controls (before treatment: n = 55; after discontinuation: n = 45). At baseline, the mean AMH level of the CPP girls was 5.9 ± 3.6 ng/mL. The mean AMH level after 3 months of the GnRH agonist treatment was lower (4.7 ± 3.2 ng/mL, P = 0.047) than that at baseline and recovered after 12 months of treatment. Six months after discontinuation, the AMH levels were similar to those at pre-treatment. Before and after the GnRH agonist treatment, the AMH levels were similar to those of the bone age-matched controls. In the precocious puberty girls, the AMH levels based on the GnRH agonist treatment stage were all within the normal reference range. The results of this study suggest that GnRH agonist treatment has no adverse effects on the reproductive function., Graphical Abstract

It is well-known that the prevalence of attention deficit hyperactivity disorder (ADHD) is higher in epileptic children than in the general pediatric population. The aim of this study was to compare the accompaniment of ADHD in epileptic children with well-controlled seizures and no significant intellectual disability with that in healthy controls. We included epileptic children between the ages of 6 and 12 yr visiting our clinic for six consecutive months and controls without significant medical or psychiatric illnesses. We excluded patients with intellectual disability or persistent seizures during the recent three months. The diagnosis of ADHD was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV). After exclusion of 84 patients, we enrolled 102 (54.8%) children (mean age, 9.4 ± 2.0 yr). Seven (7 of 102, 6.9%) were diagnosed with ADHD. As compared to control group (4 of 110, 3.6%), there was no difference in ADHD accompaniment (P = 0.29). No difference was observed in ADHD accompaniment according to seizure type and epilepsy syndrome. In conclusion, the accompaniment of ADHD in epileptic children with well-controlled seizures and no intellectual disability may not differ from that of the general pediatric population.

Central precocious puberty (CPP) is caused by premature activation of hypothalamic gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin and G-protein coupled receptor-54 system is the essential gatekeeper of the reproductive system, playing a key role in the activation of the gonadotropic axis at puberty. We aimed to determine whether serum kisspeptin may function as a marker for CPP by investigating serum kisspeptin levels in Korean girls with CPP and their prepubertal controls. Serum kisspeptin levels of Korean girls with CPP (n = 30) and age-matched healthy prepubertal controls (n = 30) were measured with a competitive enzyme immunoassay. Serum kisspeptin levels were significantly higher in CPP group than in control group (4.61 ± 1.78 vs 2.15 ± 1.52 pM/L, P < 0.001). Serum kisspeptin was positively correlated with peak luteinizing hormone (LH), peak/basal LH ratio and peak LH/follicular-stimulating hormone (FSH) ratio during GnRH stimulation test. CPP is supposed to be triggered by premature increase of kisspeptin. Serum kisspeptin may be used as a marker of CPP. Further studies on KISS1 gene polymorphisms leading to higher risk of premature increase of kisspeptin and upstream regulator of kisspeptin are also needed.

One of the major goals in investigating children with urinary tract infection (UTI) is to recognize patients at risk of further UTI-related problems. This study reports the clinical features of 19 pediatric patients with UTIs in whom associated hepatic and/or pulmonary nodules were incidentally diagnosed by the imaging tests performed for the UTI. Hepatic nodules in five patients were detected on ultrasound scans, and pulmonary nodules and both hepatic and pulmonary nodules were detected in 12 and two children by dimercaptosuccinic acid scintigraphy. The mean age of the patients was 24.5 months. Vesicoureteral reflux (VUR) was detected in nine of 17 patients (52.9%), acute pyelonephritis was identified in nine of 18 patients, and renal scarring was found in 57.1% patients with pyelonephritis. On follow-up, the hepatic and/or pulmonary nodules regressed in all patients. About 85.7% of patients experienced a recurrence of UTI within 1 year. In comparison with age- and sex-matched controls with UTIs without pulmonary or hepatic nodules, the presence of VUR and the recurrence of UTI within 1 year were higher in patients with UTIs and nodules (P

Hyponatremia and hyperkalemia in infancy can be attributed to various causes, originating from a variety of renal and genetic disorders. Pseudohypoaldosteronism type 1 (PHA1) is one of these disorders, causing mineralocorticoid resistance that results in urinary salt wasting, failure to thrive, metabolic acidosis, and dehydration. PHA1 is heterogeneous in etiology. Inactivating mutations in the NR3C2 gene (4q31.1), which encodes the mineralocorticoid receptor, causes a less severe autosomal dominant form that is restricted to the kidney, while mutations in the amiloride-sensitive epithelial sodium channel gene (alpha subunit=SCNN1A, 12p13; beta subunit=SCNN1b, 16p12.2-p12.1; gamma subunit=SCNN1G, 16p12) causes a more severe autosomal recessive form, which has systemic effects. Here we report a neonatal case of kidney restricted PHA1 (renal type of PHA1) who first showed laboratory abnormalities before obvious PHA1 manifestations, with two functional polymorphisms in the NR3C2 gene. This is the second genetically confirmed case in Korea and the first to show functional polymorphisms that have previously been reported in the literature.

Objectives Bone plays metabolic roles through osteocalcin(OC) when it is released into the systemic circulation in uncarboxylated form. Identified novel metabolic roles of OC include increasing insulin secretion and sensitivity, energy expenditure, reduction of fat mass and mitochondrial proliferation and functional enhancement. The onset of puberty can be influenced metabolic factors. This study was aimed to determine serum OC levels in girls with central precocious puberty(CPP) and to investigate the effects of OC on the onset of puberty.

Background: Earlier and more accurate identification of a high-risk group of preterm infants that are likely to develop a hemodynamically significant patent ductus arteriosus (hsPDA) would allow specific targeting of early treatment and thus possibly minimize the morbidity and mortality associated with a PDA in extremely low birth weight (ELBW) infants. Objective: To investigate the predictability of B-type natriuretic peptide (BNP) for early targeted treatment of hsPDA in ELBW infants. Methods: 73 ELBW infants that underwent echocardiographic evaluation and plasma BNP measurement after birth were enrolled. 31 infants developed hsPDA (HsPDA group) and 42 infants did not develop hsPDA (nPDA group). Results: BNP levels of the HsPDA group were significantly higher than those of the nPDA group at 24 h of age (921 [318–2,133] vs. 152 [91–450] pg/ml) but not different at 12 h of age. BNP levels at 24 h of age were significantly correlated with the magnitudes of the ductal shunt but not at 12 h of age. The area under the receiver operator characteristic curve of BNP levels for prediction of hsPDA at 24 h of age was 0.830. At the cutoff BNP levels of 200 and 900 pg/ml at 24 h of age, sensitivity was 83.9 and 54.8% and specificity was 61.9 and 95.2%, respectively. Conclusions: BNP levels at 24 h of age can be used as a guide for early targeted treatment of hsPDA and avoid the unnecessary use of cyclooxygenase inhibitors in ELBW infants.

Thirty-eight obese Korean children (21 boys, 17 girls), whose ages were between 9 and 15, were divided into either the intervention group (19 obese children: BMI>95P) or the age- and sex-matched obese control group. The intervention group performed an intensive exercise program under the supervision of educated instructors for 12 weeks (90 minutes/day, two days/week) and received lifestyle modification counseling using food diaries and phone calls. The control group participated in conventional counseling at an out-patient clinic. The intervention group appeared to have more improvement of body weight, body composition, serum lipid profiles and high-sensitivity C-reactive protein (hs-CRP) levels (P < 0.05) but without changes in serum adiponectin level. HOMA-IR decreased from 2.3 to 1.3 in the intervention group. Maximal oxygen consumption (VO2 max) and other physical fitness parameters were significantly improved after the intervention program (P < 0.05).

Purpose User-created content (UCC) has provided a considerable amount of medical information and become an important source. We aimed to evaluate the quality and scientific accuracy of precocious puberty-related UCC on YouTube. Methods The keywords "precocious puberty", "early puberty", "sexual precocity", and "precocity" were searched for on YouTube during June and July 2014. More than 1,500 UCC matched the keywords. According to the information provider, UCC was classified as medical, oriental, or commercial & others. We evaluated the quality and scientific accuracy of the information provided in UCC using the DISCERN instrument and information scores, respectively. Results We selected 51 UCC, which were categorized into three types: medical (n=17), oriental (n=17), or commercial & others (n=17). The overall quality score for medical UCC (3.4) was significantly higher relative to those of oriental and commercial & others UCC (2.8 and 2.3, respectively) (P

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.

Purpose: The objective of this study was to evaluate the effect of gonadotropin releasing hormone analog (GnRHa) treatment on bone mineral density (BMD) in girls with central precocious puberty (CPP). Further we investigated the differences in the effect on BMD by using the GnRHa leuprolide-acetate and triptorelin. Methods: Sixty-one females with CPP were enrolled in the study, the lumbar spine BMD was measured by dual energy x-ray absorptiometry before treatment, after one year (n = 61) and after two years (n = 24) of treatment. Lumbar spine BMD standard deviation scores (SDS) were compared according to chronological age (CA) and bone age (BA) for the whole group, as well as for the group A, treated with leuprolide-acetate (n = 40), and the group B, treated with triptorelin (n = 21). Results: All subjects showed significant increment in BMD during treatment (P ˂ 0.05). Lumbar spine BMD SDS for CA and BA showed no significant changes before and during treatment. Group A and group B, within each group, showed no significant changes in lumbar spine BMD SDS for CA and BA during treatment. Conclusion: Our study suggests that lumbar spine BMD was not impaired in girls treated with GnRHa for CPP and both leuprolide-acetate and triptorelin showed comparable effects on lumbar spine BMD during treatment. (J Korean Soc Pediatr Endocrinol 2011;16:106-111)

Retinol binding protein 4 (RBP4) has been postulated to provide a new link between obesity and insulin resistance. We aimed to assess the relationship between serum RBP4 and insulin resistance by investigating serum RBP4 levels in children and adolescents according to degree of obesity and pubertal stage. A total of 103 (30 lean, 39 overweight, 34 obese) were evaluated for serum RBP4, adiponectin, insulin, glucose and lipid profiles. RBP4 levels of obese and overweight groups were higher than those of lean group. RBP4 level was higher in pubertal group than in prepubertal group. RBP4 was positively correlated with age, height, weight, body mass index (BMI), abdominal circumference, systolic blood pressure, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), total cholesterol and triglyceride, and inversely with adiponectin. In the multiple linear regression analysis, RBP4 was found to be independently associated with pubertal stage, BMI and triglyceride but not with HOMA-IR. In conclusion, serum RBP4 level is related with degree of adiposity and pubertal development. The association of RBP4 with insulin resistance is supposed to be secondary to the relation between RBP4 and adipose tissue in children and adolescents.

Tuberculosis is primarily a pulmonary disease, but extra-pulmonary manifestations are not uncommon, especially in children and adolescents. Ten percent of extra pulmonary tuberculosis localizes to the bones and joints, and 56% of such cases affect the spine. We treated a childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy in a patient without specific constitutional symptoms. We report this case because the patient had an unusual presentation of spinal tuberculosis.

Background: The aim of this study was to investigate the favorable factors for gonadotropin-releasing hormone (GnRH) agonist treat ment with regard to the growth velocity and the predicted adult height (PAH) in central precocious puberty (CPP) girls. Methods: We reviewed the clinical and auxological parameters in 46 CPP girls who were treated with GnRH agonist at the pediatric endocrinology clinic of Korea University Hospital from January 2001 to August 2007. We divided the two groups according to the growth velocity of 5 cm/yr and we assessed the related factors associated with growth velocity. We also assessed the changes in PAH for two years. Results: The pretreatment chronological age and bone age were significantly younger in the high growth velocity group (> 5 cm/yr) compared to that of the low growth velocity group (7.8 ± 0.9 year vs. 8.4 ± 0.5 year, 9.4 ± 1.2 year vs. 10.1 ± 0.9 year, respectively) (P 5 cm/yr)( P < 0.05). Growth velocity during treatment had negative correlation with the pretreatment chronological age and positive correlation with the PAH after one and two years of treatment (r = -0.45, P < 0.05 and r = 0.51, P < 0.01). PAH had positive correlation with the treatment duration (r = 0.31, P < 0.05). Conclusion: In our study, the growth velocity during GnRH agonist treatment was negatively related to age at the initiation of treatment. Therefore, earlier treatment is important to improve the outcomes and to maintain appropriate growth velocity in CPP girls. (Endocrinol Metab 25:206-212, 2010)

Purpose : With a duration of action of approximately 24 hours and peakless levels, Lantus is a more physiologic basal insulin analogue compared with NPH. The aim of this study was to compare the glycemic control of Lantus plus Humalog with that of premixed insulin in children and adolescents with type 1 diabetes mellitus. Methods : The subjects consisted of 25 patients with type 1 diabetes mellitus, aged 12-19 years, who changed their insulin regimen from premixed insulin to Lantus plus Humalog. Daily insulin doses, frequency of hypoglycemia, fasting blood glucose, C-peptide concentration and HbA1c before and 6 months after Lantus treatment were compared. 24 hour blood glucose of 11 patients among Lantus treatment group (n=25) and premixed insulin treatment group (n=10) were self-monitored and compared. Results : 6 months after Lantus treatment, the episodes of hypoglycemia were reduced by 50%(15.1 vs. 7.6 events/month), especially nocturnal hypoglycemia by 67%(6.7 vs. 2.5 events/month). HbA1c was reduced from 9.3% to 8.7% after Lantus treatment. Self-monitored blood glucose of Lantus treatment group at postbreakfast 30, 60, 90 and 120 minutes were 171.1, 169.5, 171.0 and 154.1 mg/dL respectively and lower than those of premixed insulin treatment group (259.7, 282.7, 280.0 and 250.9 mg/dL respectively). Conclusion : Compared with premixed insulin, Lantus plus Humalog is more effective in glycemic control and reduction in nocturnal hypoglycemia in children and adolescents with type 1 diabetes mellitus.

Vitamin D deficiency is reported in patients with type 1 diabetes mellitus (T1DM). Allelic variations in the gene associated with vitamin D metabolism were reported to play a role in glucose metabolism. CYP2R1 and CYP27B1 gene polymorphisms were investigated as a candidate gene for T1DM in Korean youth. We measured serum level of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in 217 subjects and defined vitamin D deficiency as 25-hydroxyvitamin D level below 20 ng/ml. Five single nucleotide polymorphisms (SNPs) in the CYP2R1 gene and three SNPs in the CYP27B1 gene were examined in 92 patients with T1DM and 125 controls. The frequency of A/G alleles of the rs12794714 was 35.9%/64.1% and 46.0%/54.0% in T1DM youth and controls, respectively (p=0.034). The G/A alleles of the rs10766196 was 37.0%/63.0% and 46.0%/54.0% in T1DM youth and controls, respectively (p=0.059). We observed that the GG homozygous genotype of rs12794714 and AA homozygous genotype of rs10766196 were more prevalent in T1DM youth than in controls (42.4% vs. 29.6%, p=0.051 and 41.3% vs. 29.6%, p=0.073, respectively). The prevalence of vitamin D deficiency was considerably higher in T1DM youth with ‘G’ allele of rs12794714 and ‘A’ allele of rs12794714. Polymorphisms in CYP2R1 gene are associated with susceptibility to T1DM in Korean youth. The pathophysiological mechanisms remain unexplained, but they could be related to an etiological role for vitamin D deficiency in T1DM.