Seong Yong Lee

Signalling through the type 1 insulin-like growth factor receptor (IGF1R) interacts with canonical Wnt signalling to promote neural proliferation in developing brain

Signalling through the IGF1R [type 1 IGF (insulin-like growth factor) receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin−KO mice) the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i) the activity of a LacZ (β-galactosidase) reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene) and (ii) the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I) in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic) mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin−KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β) significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i) retarded brain growth, (ii) reduced precursor proliferation and (iii) decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

Urinary 6-sulfatoxymelatonin level in girls and its relationship with obesity

Purpose Short sleep duration is associated with obesity. Urinary 6-sulfatoxymelatonin (6-OHMS), the principal metabolite of melatonin, is closely related with sleep. We evaluated the difference in urinary 6-OHMS levels between obese girls and normal weight girls, and the relationship of urinary 6-OHMS with other hormones regulating body weight and metabolism. Methods A total of 79 girls (6.3 to 12.4 years) were included in this study, of whom 34 were obese; 15, overweight; and 30, normal-weight. We examined their pubertal status and bone age. Fasting serum levels of total ghrelin, leptin, insulin, and first morning urinary 6-OHMS were measured. Homeostatic model assessment-insulin resistance (HOMA-IR) was calculated from the fasting insulin and glucose levels. Results There was no significant difference in the creatinine adjusted 6-OHMS levels between the obese girls and the control group. Urinary 6-OHMS did not show any correlations with body mass index (BMI), BMI percentile, total ghrelin, leptin, and HOMA-IR. Negative correlations were found between urinary 6-OHMS levels and chronological and bone ages. Conclusion Our results suggest that melatonin production is not reduced consistently in obese girls.

Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance.

Lee YA, Yoo JH, Kim JH, Lee SH, Kim JH, Lim HH, Kang MJ, Chung HR, Lee SY, Shin CH, Yang SW. Independent relationships of obesity and insulin resistance with serum proinsulin level in prepubertal children with normal glucose tolerance.

Influence of Body Mass Index on the Growth Hormone Response to Provocative Testing in Short Children without Growth Hormone Deficiency

Obesity and its related factors are known to suppress the secretion of growth hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the peak GH response to provocative testing in short children without GH deficiency. We conducted a retrospective review of medical records of 88 children (2-15 yr old) whose height was less than 3 percentile for ones age and sex, with normal results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF-1 level were measured. Univariate analysis showed that the BMI standard deviation score (SDS) correlated negatively with the natural log (ln) of the peak stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with ln peak GH level induced by clonidine but not by dopamine. In stepwise multivariate regression analysis, BMI SDS was the only significant predictor of ln peak GH level in the combination of tests and the clonidine test, but not in the dopamine test. In children without GH deficiency, BMI SDS correlates negatively with the peak GH level. BMI SDS should be included in the analysis of the results of GH provocation tests, especially tests with clonidine.

Growth after Hematopoietic Stem Cell Transplantation in Children with Acute Myeloid Leukemia

Previous studies have shown that hematopoietic stem cell transplantation (HSCT) may result in growth impairment. The purpose of this study was to evaluate the growth during 5 yr after HSCT and to determine factors that influence final adult height (FAH). We retrospectively reviewed the medical records of acute myeloid leukemia (AML) patients who received HSCT. Among a total of 37 eligible patients, we selected 24 patients who began puberty at 5 yr after HSCT (Group 1) and 19 patients who reached FAH without relapse (Group 2). In Group 1, with younger age at HSCT, sex, steroid treatment, hypogonadism and hypothyroidism were not significantly associated with growth impairment 5 yr after HSCT. History of radiotherapy (RT) significantly impaired the 5 yr growth after HSCT. Chronic graft-versus-host disease (cGVHD) only temporarily impaired growth after HSCT. In Group 2, with younger age at HSCT, steroid treatment and hypogonadism did not significantly reduce FAH. History of RT significantly reduced FAH. Growth impairment after HSCT may occur in AML patients, but in patients without a history of RT, growth impairment seemed to be temporary and was mitigated by catch-up growth.

Factors Associated with the Presence and Severity of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Korean Children and Adolescents

The aim of this study was to identify the risk factors for presence and severity of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in Korean children and adolescents. A retrospective chart review of children and adolescents newly diagnosed with T1DM was conducted in seven secondary and tertiary centers in Korea. Eligible subjects were < 20 years of age and had records on the presence or absence of DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, height, body weight, pubertal status, family history of diabetes, delayed diagnosis, preceding infections, health insurance status, and parental education level. A total of 361 patients (male 46.3%) with T1DM were included. Overall, 177 (49.0%) patients presented with DKA at T1DM diagnosis. Risk factors predicting DKA at T1DM diagnosis were age ≥ 12 years, lower serum C-peptide levels, presence of a preceding infection, and delayed diagnosis. Low parental education level and preceding infection increased the severity of DKA. These results suggest that alertness of the physician and public awareness of diabetes symptoms are needed to decrease the incidence and severity of DKA at T1DM diagnosis.

Unfavorable Course of Subclinical Hypothyroidism in Children with Hashimoto’s Thyroiditis Compared to Those with Isolated Non-Autoimmune Hyperthyrotropinemia

Subclinical hypothyroidism (SCH) is a common problem in pediatric population, and the natural history of SCH varies depending on its etiology. Whether Hashimoto’s thyroiditis (HT) negatively affects the natural course of SCH was investigated in pediatric patients without concomitant diseases. Predictors for levothyroxine medication were also evaluated. Medical records of 109 children with SCH (91 girls, 5−18 years) diagnosed between 2005 and 2014 were retrospectively reviewed. Patients were classified into HT (n = 37) and isolated non-autoimmune hyperthyrotropinemia (iso-NAHT, n = 72). During median 2 years of follow-up, only 10.1% of SCH patients eventually initiated levothyroxine, and HT patients showed a higher probability of requiring levothyroxine medication than iso-NAHT patients (21.6% vs. 4.2%). Underlying HT independently predicted deterioration of thyroid function, leading to levothyroxine medication (hazard ratios [HRs], 4.6 vs. iso-NAHT, P = 0.025). High titers of anti-thyroglobulin antibodies (TGAbs) predicted later medication in the HT group (HRs, 28.2 vs. normal TGAbs, P = 0.013). Most pediatric SCH showed benign and self-remitting courses. Underlying HT significantly increases the risk for levothyroxine medication, especially with high titers of TGAbs.

Perinatal factors associated with neonatal thyroid-stimulating hormone in normal newborns

Purpose This study was to evaluate the effect of neonatal, maternal, and delivery factors on neonatal thyroid-stimulating hormone (TSH) of healthy newborns. Methods Medical records of 705 healthy infants born through normal vaginal delivery were reviewed. Neonatal TSH levels obtained by neonatal screening tests were analyzed in relation to perinatal factors and any associations with free thyroxine (FT4) and 17-α hydroxyprogesterone (17OHP) levels. Results An inverse relationship was found between TSH and sampling time after birth. Twin babies and neonates born by vacuum-assisted delivery had higher TSH levels than controls. First babies had higher TSH levels than subsequent babies. Birth weight, gestational age, maternal age and duration from the rupture of the membrane to birth were not related to neonatal TSH. There were no significant differences in TSH level according to sex, Apgar scores, labor induction, the presence of maternal disease and maternal medications. There was a positive association between TSH and 17OHP level but not between TSH and FT4 level. Multiple linear regression analyses showed that sampling time, mode of delivery, birth order, and 17OHP level were significant factors affecting neonatal TSH level. Conclusion Neonatal TSH levels of healthy normal newborns are related with multiple factors. Acute stress during delivery may influence the neonatal TSH level in early neonatal period.

Distribution of glycated haemoglobin and its determinants in Korean youth and young adults: a nationwide population-based study

The present study aimed to describe the distribution of and to investigate the factors associated with glycated haemoglobin (HbA1c) values in Korean youth (10–19 years old) and young adults (20–29 years old). Data from the Korea Health and Nutrition Examination Survey (2011–2015) were used. A total of 6,418 participants (male 3,140 [53.2%]) aged 10–29 years were included in the analysis. Percentiles of HbA1c were calculated and HbA1c values were compared according to age, sex, and associated factors. The mean HbA1c values (% [mmol/mol]) were 5.42 ± 0.01 (35.7 ± 0.1) for youths and 5.32 ± 0.01 (34.7 ± 0.1) for young adults (P < 0.001). Male participants showed significantly higher HbA1c level than females (P < 0.001). When age was grouped into 5-year intervals, HbA1c was the highest in those aged 10–14 years and the lowest in those aged 20–24 years. After controlling for confounding variables, the HbA1c values of youths and male participants were significantly higher than those of young adults and female participants. The present study provides nationally representative data on the distribution of HbA1c values in Korean youth and young adults. There were significant differences in the level of HbA1c according to age and sex.

Factors affecting growth response to growth hormone treatment in prepubertal patients with chronic renal failure

Multiple linear regression models are built to predict either the adult height or the age at first menstruation, for girls with an idiopathic central precocious puberty.