Clinical Significance of the Fetuin-A-to-Adiponectin Ratio in Obese Children and Adolescents with Diabetes Mellitus.

Fetuin-A and adiponectin are inflammatory cytokines associated with obesity and insulin resistance. This study aimed to examine the fetuin-A-to-adiponectin ratio (FAR) in diabetic children and to determine the role of FAR. A total of 54 children and adolescents with diabetes mellitus (DM) and 44 controls aged 9-16 years were included in this study. Clinical characteristics, including plasma fetuin-A and adiponectin levels, were compared with respect to body mass index (BMI) and diabetes type. Of 98 children, 54.1% were obese, whereas 18.4% were obese and diabetic. FAR was higher in obese children with DM than in non-obese children and also in type 2 DM children than in type 1. FAR showed a stronger association with BMI than with fetuin-A and adiponectin individually, and its association was more prominent in diabetic children than in controls. BMI was a risk factor for increased FAR. Plasma fetuin-A was elevated in obese children, and its association with insulin resistance and ß cell function seemed more prominent in diabetic children after adjustment for adiponectin. Thus, FAR could be a useful surrogate for the early detection of childhood metabolic complications in diabetic children, particularly those who are obese.

Transient Hyperinsulinemic Hypoglycemia Linked to PAX6 Mutation.

Prolonged hyperinsulinemic hypoglycemia in infancy can result in developmental sequelae. A mutation in the paired box-6 gene (PAX6) has been reported to cause disorders in oculogenesis and neurogenesis. A limited number of cases of diabetes mellitus in adults with a PAX6 mutation suggest that the gene also plays a role in glucose homeostasis. The present case report describes a boy with a PAX6 mutation, born with anophthalmia, who underwent hypoglycemic seizures starting at 5 months old, and showed a prediabetic condition at 60 months. This patient provides novel evidence that connects PAX6 to glucose homeostasis and highlights that life-threatening hypoglycemia or early onset glucose intolerance may be encountered. The role of PAX6 in glucose metabolism and insulin regulation should be further investigated.

Discriminatory performance of insulin-like growth factor 1 and insulin-like growth factor binding protein-3 by correlating values to chronological age, bone age, and pubertal status for diagnosis of isolated growth hormone deficiency.

PURPOSE: The discriminatory performance of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) was investigated by correlating their values with chronological age (CA), bone age (BA), and pubertal status (PS) for diagnosis of isolated growth hormone deficiency (IGHD). METHODS: We evaluated IGF-1 and IGFBP-3 levels in 310 short-stature subjects subdivided into 2 groups: IGHD (n=31) and non-IGHD (n=279). IGF-1 and IGFBP-3 were assayed using immune-radiometric assay and transformed into standard deviation score (SDS) according to CA, BA, and PS. RESULTS: The highest sensitivity was found in IGF-1-SDS for CA and IGFBP-3-SDS for CA (22.6% and 30.0%, respectively). The highest specificity was found in IGF-1-SDS for PS and IGFBP-3-SDS for PS (98.2% and 94.4%, respectively). Groups with the highest positive predictive values were IGF-1-SDS for BA and IGFBP-3-SDS for BA (10.9% and 5.1%, respectively). Highest negative predictive values were seen in IGF-1-SDS for CA and IGFBP-3-SDS for CA (98.4% and 98.4%, respectively). CONCLUSION: IGF-1-SDS for CA, instead of IGF-1-SDS for BA or PS, could be used as a standard variable for IGHD screening. The sufficiently high specificity of IGF-1-SDS for PS suggests that this value is a useful tool for identification of IGHD.

HLA alleles, especially amino-acid signatures of HLA-DPB1, might contribute to the molecular pathogenesis of early-onset autoimmune thyroid disease.

The major histocompatibility complex region has been suggested to play an important role in the development of autoimmune thyroid disease (AITD). In this study, we investigated the associations of human leukocyte antigen (HLA) alleles and amino acid variants of HLA with early-onset AITD. HLA class I and class II genes were analyzed in 116 Korean children with AITDs (Graves' disease [GD]: 71, Hashimoto's disease [HD]: 45) and 142 healthy controls. HLA-B*46:01 (OR = 3.96, Pc = 0.008), -C*01:02 (OR = 2.51 Pc = 0.04), -DPB1*02:02 (OR = 3.99, Pc = 0.04), and -DPB1*05:01 (OR = 4.6, Pc = 0.003) were significantly associated with GD, and HLA-A*02:07 (OR = 4.68, Pc = 0.045) and -DPB1*02:02 (OR = 6.57, Pc = 0.0001) with HD. The frequency of HLA-DPB1*05:01 was significantly higher in GD patients than in HD patients (Pc = 0.0005). Furthermore, differences were found between patients with Thyroid associated ophthalmopathy (TAO) and those without TAO in the distribution of HLA-B*54:01 (8.6% vs. 30.6%, P = 0.04) and -C*03:03 (37.1% vs. 11.1%, P = 0.02). In the analysis of amino acid variants of HLA molecules, both Leu35 (OR = 23.38, P = 0.0002) and Glu55 (OR = 23.38, P = 0.0002) of HLA-DPB1 were strongly associated with GD and showed different distributions between GD and HD (P = 0.001). Our results suggest that HLA alleles, especially amino-acid signatures of the HLA-DP ß chain, might contribute to the molecular pathogenesis of early-onset AITD.

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty.

PURPOSE: We investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP). METHODS: Medical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age). RESULTS: The peak LH (8.95±2.85 U/L vs. 11.97±8.42 U/L, P<0.01) and peak follicle-stimulating hormone (9.60±2.91 U/L vs. 11.17±7.77 U/L, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81-0.98, P=0.02). CONCLUSION: In girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty.

Nonautoimmune congenital hyperthyroidism due to p.Asp633Glu mutation in the TSHR gene.

Most cases of congenital hyperthyroidism are autoimmune forms caused by maternal thyroid stimulating antibodies. Nonautoimmune forms of congenital hyperthyroidism caused by activating mutations of the thyrotropin receptor (TSHR) gene are rare. A woman gave birth to a boy during an emergency cesarean section at 33 weeks of gestation due to fetal tachycardia. On the 24th day of life, thyroid function tests were performed due to persistent tachycardia, and hyperthyroidism was confirmed. Auto-antibodies to TSHR, thyroid peroxidase, and thyroglobulin were not found. The patient was treated with propylthiouracil and propranolol, but hyperthyroidism was not well controlled. At 3 months of age, the patient had craniosynostosis and hydrocephalus, and underwent a ventriculoperitoneal shunt operation. Direct sequencing of the TSHR gene showed a heterozygous mutation of c.1899C>A (p.Asp633Glu) in exon 10. No mutations were discovered in any of the parents in a familial genetic study. We have reported a case of sporadic nonautoimmune congenital hyperthyroidism, by a missense mutation of the TSHR gene, for the first time in South Korea.

Association of Polymorphisms in Toll-Like Receptors 4 and 9 with Autoimmune Thyroid Disease in Korean Pediatric Patients.

BACKGROUND: Toll-like receptors (TLRs) have been suggested to be associated with the development of AITD. METHODS: Fifteen single-nucleotide polymorphisms in 7 TLR genes were analyzed in 104 Korean children (girls = 86, boys = 18) with AITD (Hashimoto disease (HD) = 44, Graves' disease (GD) = 60, thyroid-associated ophthalmopathy (TAO) = 29, and non-TAO = 31) with 183 controls. RESULTS: GD showed higher frequencies of the TLR4 rs1927911 C allele than control. TAO showed a lower frequency of the TLR4 rs1927911 CT genotype and non-TAO showed a higher frequency of the TLR4 rs1927911 CC genotype than control. The frequency of the TLR9 rs187084 CC genotype in TAO was higher than that in non-TAO. GD females showed a higher frequency of the TLR4 rs10759932 T allele, rs1927911 CC genotype, and the rs1927911 C allele than controls. GD males showed a higher frequency of the TLR4 rs10759932 CC genotype and rs1927911 TT genotype and lower frequency of the rs1927911 CT genotype than control. The frequency of the TLR4 rs10759932 CC genotype, C allele and rs1927911 TT genotype, and T allele in a GD female were lower than in a GD male. CONCLUSIONS: Our results suggest that TLR4 and 9 polymorphisms might contribute to the pathogenesis of GD and TAO.

Birth Weight Could Influence Bone Mineral Contents of 10- to 18-Year-Old Korean Adolescents: Results from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010.

BACKGROUND: We investigate the relationship between birth weight (BW) and bone mineral content (BMC) in Korean adolescents. METHODS: Data were obtained from the Korea National Health and Nutrition Examination Survey conducted in 2010. Baseline characteristics were compared according to age- and sex-specific BMC quartiles of total body less head (TBLH), lumbar spine (LS) and femur neck (FN) in 10- to 18-year-old adolescents (male = 474, female = 394). RESULTS: BW showed a positive correlation with current weight-SDS (p = 0.006 in males, p = 0.008 in females). BW according to TBLH-BMC quartile groups (p for trend <0.003 in males, <0.0001 in females), LS-BMC quartile groups (p for trend <0.034 in males) and FN-BMC quartile groups (p for trend <0.008 in males, <0.020 in females) showed significant differences. The odds ratio (OR) of being in the highest BMC quartile, per 1-kg increase in BW, was significantly increased in TBLH-BMC (OR = 2.14 in males, OR = 3.26 in >16-year-old adolescents) and FN-BMC (OR = 2.62 in males, OR = 3.06 in >16-year-old adolescents) after adjusting for age, height, smoking, drinking, metabolic equivalent of task, and gestational age. CONCLUSION: BW might be one of the determinant factors of BMC in Korean adolescents.