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1.  Efficacy of Short-Term Growth Hormone Treatment in Prepubertal Children with Idiopathic Short Stature 
Yonsei Medical Journal  2013;55(1):53-60.
It has been reported that daily recombinant human growth hormone (GH) treatment showed beneficial effects on growth in prepubertal children with idiopathic short stature (ISS). The present study aimed to validate the GH (Eutropin®) effect on growth promotion and safety after short-term GH treatment.
Materials and Methods
This study was an open-label, multicenter, interventional study conducted at nine university hospitals in Korea between 2008 and 2009. Thirty six prepubertal children with ISS were enrolled in this study to receive 6-month GH treatment. Yearly growth rate, height standard deviation score (SDS), and adverse events were investigated during treatment.
After 26 weeks of GH treatment, the height velocity significantly increased by 6.36±3.36 cm/year (p<0.001). The lower end of one-sided 95% confidence interval was 5.22 cm/year, far greater than the predefined effect size. The gain in height SDS at week 26 was 0.57±0.27 (p<0.0001). Bone age significantly increased after GH treatment, however, bone maturation rate (bone age for chronological age) showed limited advancement. This 26-week GH treatment was effective in increasing serum levels of insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 from baseline (p<0.0001). Eutropin was well tolerated and there were no withdrawals due to adverse events. No clinically significant changes in laboratory values were observed.
This 6-month daily GH treatment in children with ISS demonstrated increased height velocity, improved height SDS, and increased IGF-I and IGFBP-3 levels with a favorable safety profile.
PMCID: PMC3874918  PMID: 24339287
Treatment outcome; safety; growth hormone; child; short stature; idiopathic
2.  Spot Urine Albumin to Creatinine Ratio and Serum Cystatin C are Effective for Detection of Diabetic Nephropathy in Childhood Diabetic Patients 
Journal of Korean Medical Science  2012;27(7):784-787.
Spot urinary albumin to creatinine ratio (ACR) measurement has been suggested as a surrogate to 24-hr urine collection for the assessment of microalbuminuria, and cystatin C (cysC) is known as an advantageous marker for renal function. The aim of this study was to evaluate the clinical values of spot urinary ACR and serum cysC for the assessment of diabetic nephropathy instead of 24-hr urine microalbumin in children and adolescents with diabetes. A total of 113 children and adolescents (age 12-19 yr, M:F = 47:66) with type 1 or 2 diabetes were enrolled. We evaluated the validity of spot urine ACR and serum cysC, and then compared them to 24-hr urine microalbumin and creatinine clearance. Spot urine ACR was correlated with 24-hr urine albumin excretion (R2 = 0.828, P = 0.001) and creatinine clearance (R2 = 0.249, P = 0.017). The ROC curve analysis of serum cysC demonstrated higher diagnostic accuracy than that of serum creatinine (AUC 0.732 vs 0.615). Both the measurements of spot urine ACR and serum cysC might better predict the presence of diabetic nephropathy than 24-hr urine microalbumin in childhood diabetic patients.
PMCID: PMC3390728  PMID: 22787375
Diabetic Nephropathies; Albumin to Creatinine Ratio; Cystatin C; Childhood Diabetes
3.  Effects of Body Composition, Leptin, and Adiponectin on Bone Mineral Density in Prepubertal Girls 
Journal of Korean Medical Science  2010;25(8):1187-1190.
Body weight is positively associated with bone mineral density but the relationship between obesity and bone mineral density is unclear. Leptin and adiponectin are potential independent contributors to bone mineral density. We assessed the correlations of body composition, leptin and adiponectin with bone mineral density, and whether leptin, adiponectin and body composition determine bone mineral density independently in prepubertal girls. Forty-eight prepubertal girls were classified into obese and control groups by body mass index. Serum leptin and adiponectin levels were determined by enzyme immunoassay. Bone mineral density was measured using dual energy radiography absorptiometry and body composition was measured using bioelectrical impedance analysis. Lean and fat mass, and leptin were positively correlated with bone mineral density. Lean mass was a positive independent predictor of femoral and L-spine bone mineral density. Serum leptin was a postivie independent predictor of femoral bone mineral density. Fat mass was a negative independent predictor of femoral bone mineral density. In prepubertal girls, lean mass has a favorable effect on bone mineral density. Fat mass seems not to protect the bone structure against osteoporosis, despite increased mechanical loading. Serum leptin may play a biological role in regulating bone metabolism.
PMCID: PMC2908789  PMID: 20676331
Bone Density; Body Composition; Leptin; Adiponectin; Obesity
4.  Ultrasound measurement of pediatric visceral fat thickness: correlations with metabolic and liver profiles 
Abdominal obesity is a fundamental factor underlying the development of metabolic syndrome. Because of radiation exposure and cost, computed tomography or dual-energy X-ray absorptiometry to evaluate abdominal adiposity are not appropriate in children. Authors evaluated whether ultrasound results could be an indicator of insulin resistance and nonalcoholic fatty liver disease (NAFLD).
We enrolled 73 subjects (aged 6–16 years) who were evaluated abdominal adiposity by ultrasound. Subcutaneous fat thickness was defined as the measurement from the skin-fat interface to the linea alba, and visceral fat thickness (VFT) was defined as the thickness from the linea alba to the aorta. Anthropometric and biochemical metabolic parameters were also collected and compared. The subjects who met 2 criteria, radiologic confirmed fatty liver and alanine aminotransferase >40, were diagnosed with NAFLD.
There was a strong positive correlation between VFT and obesity. VFT was highly correlated with the homeostasis model assessment for insulin resistance score (r=0.403, P<0.001). The area under the curve for VFT as a predictor of NAFLD was 0.875 (95% confidence interval [CI], 0.787–0.964). VFT of 34.3 mm was found to be the discriminating cutoff for NAFLD (sensitivity, 84.6%; specificity, 71.2%, respectively).
Ultrasound could be useful in measuring VFT and assessing abdominal adiposity in children. Moreover, increased VFT might be an appropriate prognostic factor for insulin resistance and NAFLD.
PMCID: PMC4960018  PMID: 27462583
Intra-abdominal fat; Ultrasonography; Child; Abdominal obesity metabolic syndrome; Fatty liver
5.  A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report 
A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.
PMCID: PMC4835561  PMID: 27104179
Pituitary microadenoma; Inferior petrosal sinus sampling; Desmopressin
6.  Male patients presenting with rapidly progressive puberty associated with malignant tumors 
In males, precocious puberty (PP) is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years) with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG) levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years) and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.
PMCID: PMC4835563  PMID: 27104181
Puberty; Neoplasms; Germ-cell tumor
7.  Turner syndrome with spinal hemorrhage due to vascular malformation 
Turner syndrome (TS) is a relatively common chromosomal disorder and is associated with a range of comorbidities involving the cardiovascular system. Vascular abnormalities, in particular, are a common finding in cases of TS. However, dissection involving the vertebral arteries is rare. Here, we report the case of a 9-year-old girl with TS who had been treated with growth hormone replacement therapy for the past 3 years. She presented with weakness of both lower legs, and was ultimately diagnosed with spinal hemorrhage due to vascular malformation. We treated her with intravenous high dose dexamethasone (0.6 mg/kg) and she could walk without assistance after 6 days of treatment. In conclusion, when a patient with TS shows sudden weakness of the lower limbs, we should consider the possibility of spinal vessel rupture and try to take spine magnetic resonance imaging as soon as possible. We suggest a direction how to make a proper diagnosis and management of sudden vertebral artery hemorrhage in patients with TS.
PMCID: PMC4722165  PMID: 26817012
Turner syndrome; Vascular malformations; Vertebral artery dissection
8.  Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia 
In male patients with congenital adrenal hyperplasia (CAH), the presence of testicular adrenal rest tumors (TARTs) have been reported, however their prevalence and clinical manifestations are not well known. Untreated TARTs may lead to testicular structural damage and infertility. This study was conducted to investigate the prevalence of TARTs in male patients with CAH, and characterize the manifestations to identify contributing factors to TART.
Among 102 CAH patients aged 0-30 years, 24 male patients have been regularly followed up in our outpatient clinic at Severance Children's Hospital from January 2000 to December 2014. In order to reveiw the characteristics of TART patients, we calculated the mean levels of hormones during the 5 years before the time of investigation. Five patients underwent follow-up scrotal ultrasonography (US) after adjusting the dosage of glucocorticoids.
TARTs were detected in 8 of the 13 patients (61.5%). The median age of TARTs diagnosis was 20.2 years with the youngest case being 15.5 years old. The mean serum level of adrenocorticotropic hormone (ACTH) was higher in the TARTs patient group compared to the non-TARTs group (P<0.05). The tumor size decreased in 3 cases, slightly increased in 1 case, and had no change in another case.
The serum ACTH level might be associated with the growth promoting factor for TARTs, but the exact mechanism has not been clearly identified. Screening for TARTs using US is important in male patients with CAH for early-detection and prevention of ongoing complications, such as infertility.
PMCID: PMC4623344  PMID: 26512352
Congenital adrenal hyperplasia; Adrenal rest tumor; Adrenocorticotropic hormone
9.  Hypotonic hyponatremia by primary polydipsia caused brain death in a 10-year-old boy 
Hypotonic hyponatremia by primary polydipsia can cause severe neurologic complications due to cerebral edema. A 10-year-and-4-month-old boy with a psychiatric history of intellectual disability and behavioral disorders who presented with chief complaints of seizure and mental change showed severe hypotonic hyponatremia with low urine osmolality (serum sodium, 101 mmol/L; serum osmolality, 215 mOsm/kg; urine osmolality, 108 mOsm/kg). The patient had been polydipsic for a few months prior, and this had been worse in the previous few days. A diagnosis of hypotonic hyponatremia caused by primary polydipsia was made. The patient was in a coma, and developed respiratory arrest and became brain death shortly after admission, despite the treatment. The initial brain magnetic resonance imaging showed severe brain swelling with tonsillar and uncal herniation, and the patient was declared as brain death. It has been reported that antidiuretic hormone suppression is inadequate in patients with chronic polydipsia, and that this inadequate suppression of antidiuretic hormone is aggravated in patients with acute psychosis. Therefore, hyponatremia by primary polydipsia, although it is rare, can cause serious and life-threatening neurologic complications.
PMCID: PMC4623346  PMID: 26512354
Hyponatremia; Psychogenic polydipsia; Water intoxication
10.  XYY syndrome: a 13-year-old boy with tall stature 
When evaluating the underlying causes of tall stature, it is important to differentiate pathologic tall stature from familial tall stature. Various pathologic conditions leading to adult tall stature include excess growth hormone secretion, Marfan syndrome, androgen or estrogen deficiency, testicular feminization, and sex chromosome anomaly, such as Klinefelter syndrome and XYY syndrome. Men with 47,XYY syndrome can exhibit multiple phenotypes. A 13-year-old boy visited the hospital for evaluation of tall stature. The boy had no other physical abnormalities except tall stature. All biochemical and imaging studies were within the normal ranges. He was diagnosed with XYY syndrome in this chromosome study. When evaluating men with tall stature, XYY syndrome should be ruled out.
PMCID: PMC4623347  PMID: 26512355
Growth disorders; Sex chromosome disorders; 47,XYY syndrome
13.  HbA1c variability and the risk of microalbuminuria in patients with type 1 diabetes 
PMCID: PMC4428784
HbA1c variability; microalbuminuria; type 1 diabetes
14.  Regression and progression of microalbuminuria in adolescents with childhood onset diabetes mellitus 
Although microalbuminuria is considered as an early marker of nephropathy in diabetic adults, available information in diabetic adolescents is limited. The aim of this study was to investigate prevalence and frequency of regression of microalbuminuria in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients with childhood onset.
One hundred and nine adolescents (median, 18.9 years; interquartile range (IQR), 16.5-21.0 years) with T1DM and 18 T2DM adolescents (median, 17.9 years; IQR, 16.8-18.4 years) with repeated measurements of microalbuminuria (first morning urine microalbumin/creatinine ratios) were included. The median duration of diabetes was 10.1 (7.8-14.0) years and 5.0 (3.5-5.6) years, respectively, and follow-up period ranged 0.5-7.0 years. Growth parameters, estimated glomerular filtration rate, glycosylated hemoglobin (HbA1c) and lipid profiles were obtained after reviewing medical record in each subject.
The prevalence of microalbuminuria at baseline and evaluation were 21.1% and 17.4% in T1DM, and 44.4% and 38.9% in T2DM. Regression of microalbuminuria was observed in 13 T1DM patients (56.5%) and 3 T2DM patients (37.5%), and progression rate was 10.5% and 20% in T1DM and T2DM respectively. In regression T1DM group, HbA1c at baseline and follow-up was lower, and C-peptide at baseline was higher compared to persistent or progression groups. In T2DM, higher triglyceride was observed in persistent group.
Considerable regression of microalbuminuria more than progression in diabetes adolescents indicates elevated urinary microalbumin excretion in a single test does not imply irreversible diabetic nephropathy. Careful monitoring and adequate intervention should be emphasized in adolescents with microalbuminuria to prevent rapid progression toward diabetic nephropathy.
PMCID: PMC4397268  PMID: 25883922
Albuminuria; Type 1 diabetes mellitus; Type 2 diabetes mellitus; Child; Adolescent
15.  Etiologies and characteristics of children with chief complaint of short stature 
Short stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature.
We retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed.
Approximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%).
A majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.
PMCID: PMC4397271  PMID: 25883925
Short stature; Etiology; Growth
16.  Relationship between serum 25-hydroxyvitamin D concentration and risks of metabolic syndrome in children and adolescents from Korean National Health and Nutrition Examination survey 2008-2010 
Previous studies have revealed many inconsistent results regarding the relationship between vitamin D and metabolic syndrome. The purpose of our study was to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and factors that characterize metabolic syndrome in Korean children and adolescents.
We analyzed data from 2,880 children and adolescents aged 10-18 years collected from the 2008-2010 Korean National Health and Nutrition Examination Survey. We investigated the data according to quartiles of 25(OH)D concentrations.
Systolic blood pressure and diastolic blood pressure with adjustment for sex and age differed significantly between the serum 25(OH)D groups and exhibited negative trend as 25(OH)D concentrations increased. The number of subjects with metabolic syndrome was greater in the low 25(OH)D groups (I, II, and III quartile) than in the high 25(OH)D group (IV quartile) (P=0.029). BMI and waist circumference were lower in the high 25(OH)D group. Serum 25(OH)D concentration correlated negatively with homeostasis model assessment estimate of insulin resistance (ρ=-0.073, P<0.001) and correlated positively with quantitative insulin sensitivity check index (ρ=0.095, P<0.001).
Low serum 25(OH)D level is associated with an increase of insulin resistance and metabolic syndrome in children and adolescents.
PMCID: PMC4397273  PMID: 25883927
25-hydroxyvitamin D; Metabolic syndrome; Child; Obesity; Insulin resistance
17.  Growth hormone treatment and risk of malignancy 
Korean Journal of Pediatrics  2015;58(2):41-46.
Growth hormone (GH) treatment has been increasingly widely used for children with GH deficiencies as the survival rate of pediatric patients with malignancies has increased. Both GH and insulin-like growth factor-I have mitogenic and antiapoptotic activity, prompting concern that GH treatment may be associated with tumor development. In this review, the authors examined the relationship between GH treatment and cancer risk in terms of de novo malignancy, recurrence, and secondary neoplasm. Although the results from numerous studies were not entirely consistent, this review of various clinical and epidemiological studies demonstrated that there is no clear evidence of a causal relationship between GH treatment and tumor development. Nonetheless, a small number of studies reported that childhood cancer survivors who receive GH treatment have a small increased risk of developing de novo cancer and secondary malignant neoplasm. Therefore, regular follow-ups and careful examination for development of cancer should be required in children who receive GH treatment. Continued surveillance for an extended period is essential for monitoring long-term safety.
PMCID: PMC4357770  PMID: 25774194
Growth hormone; Neoplasms; Recurrence; Malignancy insulin-like growth factor-I
18.  Adult height in girls with central precocious puberty treated with gonadotropin-releasing hormone agonist with or without growth hormone 
There is controversy surrounding the growth outcomes of treatment with gonadotropin-releasing hormone agonist (GnRHa) in central precocious puberty (CPP). We analyzed height preservation after treatment with GnRHa with and without growth hormone (GH) in girls with CPP.
We reviewed the medical records of 82 girls with idiopathic CPP who had been treated with GnRHa at Severance Children's Hospital from 2004 to 2014. We assessed the changes in height standard deviation score (SDS) for bone age (BA), and compared adult height (AH) with midparental height (MPH) and predicted adult height (PAH) during treatment in groups received GnRHa alone (n=59) or GnRHa plus GH (n=23).
In the GnRHa alone group, the height SDS for BA was increased during treatment. AH (160.4±4.23 cm) was significantly higher than the initial PAH (156.6±3.96 cm) (P<0.001), and it was similar to the MPH (159.9±3.52 cm). In the GnRHa plus GH group, the height SDS for BA was also increased during treatment. AH (159.3±5.33 cm) was also higher than the initial PAH (154.6±2.55 cm) (P<0.001), which was similar to the MPH (158.1±3.31 cm). Height gain was slightly higher than that in the GnRHa alone group, however it statistically showed no significant correlation with GH treatment.
In CPP girls treated with GnRHa, the height SDS for BA was increased, and the AH was higher than the initial PAH. Combined GH treatment showed a limited increase in height gain.
PMCID: PMC4316408  PMID: 25654068
Central precocious puberty; Gonadotropin-releasing hormone; Growth hormone; Treatment outcome
19.  Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls 
The rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH) stimulation test is required to diagnose central precocious puberty (CPP), however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.
Clinical and laboratory parameters, including basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), were measured in 540 girls with clinical signs of CPP.
Two hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group). The CPP group had advanced bone age (P<0.001), accelerated yearly growth rate (P<0.001), increased basal levels of LH (P=0.02), FSH (P<0.001), E2 (P=0.001), and insulin-like growth factor-I levels (P<0.001) compared to the non-CPP group. In contrast, body weight (P<0.001) and body mass index (P<0.001) were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L) detected CPP with 87.8% sensitivity and 20.9% specificity.
No single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.
PMCID: PMC4027085  PMID: 24904878
Precocious puberty; Diagnosis; Gonadotropin-releasing hormone; Forecasting; Female
22.  Longitudinal Standards for Height and Height Velocity in Korean Children and Adolescents: the Kangwha Cohort Study 
Journal of Korean Medical Science  2013;28(10):1512-1517.
Longitudinal standards for height and height velocity are essential to monitor for appropriate linear growth. We aimed to construct standards in Korean children and adolescents through the population-based longitudinal Kangwha study. Our study was a part of a community-based prospective cohort study from 1986 to 1999 with 800 school children. Height and height velocity were recorded annually from age 6 until final height. Results were compared with cross-sectional data from the 2007 Korean National Growth Charts. Final height was 173.5 cm in boys and 160.5 cm in girls. Although final height was similar between longitudinal and cross-sectional standards, the mean height for age was higher in the longitudinal standard by 1-4 cm from age 6 until the completion of puberty. Using the longitudinal standard, age at peak height velocity (PHV) was 12 in boys and 10 in girls; height velocity at PHV was 8.62 cm/yr in boys and 7.07 cm/yr in girls. The mean height velocity was less than 1 cm/yr at age 17 in boys and 15 in girls. Thus, we have presented the first report of longitudinal standards for height and height velocity in Korean children and adolescents by analyzing longitudinal data from the Kangwha cohort.
PMCID: PMC3792607  PMID: 24133358
Growth; Height Velocity; Longitudinal Studies; Reference Standards; Child
23.  The Clinical Measures Associated with C-peptide Decline in Patients with Type 1 Diabetes over 15 Years 
Journal of Korean Medical Science  2013;28(9):1340-1344.
This study was done to characterize the natural course of C-peptide levels in patients with type 1 diabetes and identify distinguishing characters among patients with lower rates of C-peptide decline. A sample of 95 children with type 1 diabetes was analyzed to retrospectively track serum levels of C-peptide, HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The clinical characteristics were compared between the patients with low and high C-peptide levels, respectively. The average C-peptide level among all patients was significantly reduced five years after diagnosis (P < 0.001). The incidence of diabetic ketoacidosis was significantly lower among the patients with high levels of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS) 15 yr after diagnosis were significantly higher among the patients with low C-peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C-peptide level was significantly decreased after 5 yr from diagnosis. Type 1 diabetes patients whose beta-cell functions were preserved might have low incidence of diabetic ketoacidosis. The declines of C-peptide level after diagnosis in type 1 diabetes may be associated with changes of body weight and BMI.
PMCID: PMC3763109  PMID: 24015040
Diabetes Mellitus, Type 1; C-Peptide; Body Weight; Body Mass Index; Diabetic Ketoacidosis
24.  Sex hormone binding globulin, free estradiol index, and lipid profiles in girls with precocious puberty 
Sex hormone-binding globulin (SHBG) modulates the availability of biologically active free sex hormones. The regulatory role of SHBG might be important in the relationship between hormone levels and the modification of lipid profiles in girls with precocious puberty. However, few studies have evaluated the relationship of SHBG, free estradiol index (FEI), and lipid levels in these girls.
One hundred and nine girls less than 8 years of age with pubertal development were enrolled. FEI was calculated with SHBG and estradiol (E2). We analyzed SHBG between peak luteinizing hormone (LH)≥5 (IU/L) (group 1) and LH<5 (IU/L) (group 2) through a gonadotropin releasing hormone stimulation test.
Body mass index (BMI) standard deviation score (SDS) was higher in group 2 than in group 1 (P=0.004). Serum SHBG levels did not differ and FEI was not higher in group 1 (P=0.122). Serum cholesterol, HDL, and LDL did not differ; however, triglyceride levels were higher in group 2 (P=0.023). SHBG was negatively correlated with bone age advancement, BMI, BMI SDS, and FEI, and was positively correlated with HDL. However, SHBG was not correlated with E2 or peak LH.
Serum SHBG itself might not be associated with precocious puberty in girls, but it might be related to BMI and lipid profiles. Further studies are needed to reveal the relationship between sex hormone and obesity in girls with precocious puberty.
PMCID: PMC4027091  PMID: 24904857
Sex hormone-binding globulin; Estradiol; Lipid; Precocious puberty

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