Triglyceride glucose index is superior biomarker for predicting type 2 diabetes mellitus in children and adolescents.

The triglyceride-glucose (TyG) index is associated with predicting type 2 diabetes mellitus (T2DM), but its relationship with homeostatic model assessment of insulin resistance (HOMA-IR) in T2DM is not established. We aimed to investigate the role of TyG index for detection of T2DM in children and adolescents and compare it with HOMA-IR. A cross sectional study was performed in 176 overweight or obese children and adolescents with mean age of 11.34 ± 3.24 years. TyG index was calculated as ln (fasting triglyceride (TG) [mg/dL] × fasting glucose [mg/dL]/2). Of a total of 176 subjects, 57 (32%) were diagnosed with T2DM. Significant differences were observed in the TyG index between T2DM and non-T2DM (p < 0.001). The TyG index had a positive correlation with fasting glucose (r = 0.519, p < 0.001), HOMA-IR (r = 0.189, p < 0.017), HbA1c (r = 0.429, p < 0.001), total cholesterol (TC) (r = 0.257, p = 0.001), TG (r = 0.759, p < 0.001), and low-density lipoprotein cholesterol (LDL-C)(r = 0.152, p < 0.001), and a negative correlation with high-density lipoprotein cholesterol (HDL-C)(r = -0.107, p < 0.001) after controlling for sex, age and BMI standard deviation scores (SDS). In multiple regression analyses, 91.8% of the variance in TyG index was explained by age, glucose, HOMA-IR, TG, LDL-C, and HDL-C (p < 0.001). In the receiver operating characteristic (ROC) analysis, the TyG index [area under the curve (AUC) 0.839)] showed a better performance compared to HOMA-IR (AUC 0.645) in identifying patients with T2DM (p < 0.001). In conclusion, the TyG index had significant association with insulin resistance in T2DM and was superior to HOMA-IR in predicting T2DM in children and adolescents.

Gene polymorphisms in leptin and its receptor and the response to growth hormone treatment in patients with idiopathic growth hormone deficiency.

This study aimed to investigate the relationships between genetic polymorphisms of leptin/receptor genes and clinical/biochemical characteristics in children with growth hormone deficiency (GHD). Ninety-three GHD children and 69 age-matched normal controls were enrolled. Anthropometric measurements, bone age, and laboratory test results were obtained. Polymorphisms in the LEP gene promoter locus (LEP-2548, rs7799039) and LEPR genes (K109R, rs1137100 and Q223R, rs1137101) were analyzed using PCR-RFLP. The serum leptin levels were measured using an ELISA kit. The median height and BMI z-scores of all GHD subjects were -2.20 and -0.26, respectively, and those of normal controls were -0.30 and -0.13, respectively. The serum leptin levels were similar between GHD subjects and normal controls (p = 0.537), but those were different between the complete GHD (6.97 ng/mL) and partial GHD (4.22 ng/mL) groups (p = 0.047). There were no differences in the genotypic distributions of LEP-2548, LEPR K109R, and Q223R between GHD subjects and normal controls. However, GHD subjects with the G allele at LEP-2548 showed higher IGF-1 (p = 0.047) and IGFBP-3 SDSs (p = 0.027) than GHD subjects with the A allele. GHD subjects with the G allele at LEPR Q223R showed lower stimulated GH levels (p = 0.023) and greater height gain after 1 year of GH treatment (p = 0.034) than GHD subjects with the A allele. In conclusion, leptin/leptin receptor genes are suggested to have the role of growth-related factors, which can affect various growth responses in children who share the same disease entity.

Inhibin B as a screening tool for early detection and treatment monitoring of central precocious puberty.

Anti-Müllerian hormone (AMH) and inhibin B are considered possible biomarkers of central precocious puberty (CPP). The aim of this study was to evaluate serum levels of AMH and inhibin B, to investigate their regulatory patterns, and to study their clinical significance in girls with CPP. In total, 48 girls with CPP and 35 age-matched prepubertal control girls were enrolled in the study. AMH and inhibin B levels were determined in the CPP and control groups. In the patient group, AMH and inhibin B levels were evaluated during 1 year of gonadotropin releasing hormone analog (GnRHa) treatment. The mean inhibin B level in the CPP group was significantly higher than that in the control. AMH levels were not different between the two groups. After GnRHa treatment. AMH and inhibin B levels decreased significantly. Based on the ROC analysis, the cutoff value for inhibin B to determine CPP was 19.59 pg/mL, with 83.3% sensitivity and 82.9% specificity, and the area under the curve was 0. 852. Inhibin B was useful for determining CPP and the therapeutic effects of GnRHa treatment in girls with CPP. AMH interacted, in part, with the hypothalamo-pituitary gonadal axis, but its clinical implications in CPP should be further investigated.

Identification of rare missense mutations in NOTCH2 and HERC2 associated with familial central precocious puberty via whole-exome sequencing.

Objective: Genetic factors play a critical role in pubertal progression; however, mutations associated with central precocious puberty (CPP) have been reported only in four genes: KISS1, KISS1R, DLK1, and MKRN3. This study aimed to identify novel, potentially pathogenic variants in patients with familial CPP via whole-exome sequencing (WES).Methods: WES analysis was applied in 28 patients (25 girls and three boys) belonging to 14 families, wherein all siblings were diagnosed with CPP. Data analysis aimed to select only very rare variants (minor allele frequency <1%). Nonsense, splice-site, and frameshift variants were considered the most ideal candidate variants. Additionally, non-synonymous missense variants predicted as being deleterious using in silico analysis tools were further considered.Results: The analysis of exome sequencing data resulted in the identification of rare mutations in two promising candidate genes (NOTCH2 and HERC2) in a family. Siblings with CPP exhibited two heterozygous missense mutations (p. Leu15Phe in NOTCH2 and p. Arg4081His in HERC2). Moreover, their parents without history of CPP had a missense variant in either NOTCH2 or HERC2.Conclusions: We identified new candidate genes with potential roles in pubertal development. Digenic inheritance of the two genetic mutations associated with the Notch signaling pathway may have a synergistic effect resulting in CPP.

Serum Makorin ring finger protein 3 values for predicting Central precocious puberty in girls.

This study evaluated the serum level of MKRN3 and investigated its diagnostic usefulness in girls with central precocious puberty (CPP). In total, 41 girls with CPP and 35 age-matched normal control girls were enrolled. Serum values of MKRN3 were measured in both groups. Gonadotropin and estradiol concentrations were evaluated after 6 and 12 months of GnRH agonist (GnRHa) treatment in CPP patients. The MKRN3 concentrations were much lower in the patient group than in the control group (p = .005). Over 1 year of GnRHa treatment in patients, the gonadotropin concentrations were significantly decreased (p < .05), while the MKRN3 concentrations were unchanged (p > .05). MKRN3 levels were inversely correlated to standard deviation (SD) in height (r = -0.46, p = .000), SD in weight (r = -0.32, p = .005), Tanner stage (r = -0.41, p = .000), and bone age (r = -0.46, p = .000). Based on ROC analysis, the area under curve was 0.758 for MKRN3, with 82.9% sensitivity and 68.5% specificity. The measurement of serum MKRN3 level may provide some help for CPP prediction, but relatively various values need further validation.

Multiple Endocrine Neoplasia Type 1 Presenting as Hypoglycemia due to Insulinoma.

Multiple endocrine neoplasia (MEN) mutation is an autosomal dominant disorder characterized by the occurrence of parathyroid, pancreatic islet, and anterior pituitary tumors. The incidence of insulinoma in MEN is relatively uncommon, and there have been a few cases of MEN manifested with insulinoma as the first symptom in children. We experienced a 9-year-old girl having a familial MEN1 mutation. She complained of dizziness, occasional palpitation, weakness, hunger, sweating, and generalized tonic-clonic seizure that lasted for 5 minutes early in the morning. At first, she was only diagnosed with insulinoma by abdominal magnetic resonance images of a 1.3 x 1.5 cm mass in the pancreas and high insulin levels in blood of the hepatic vein, but after her father was diagnosed with MEN1. We found she had familial MEN1 mutation, and she recovered hyperinsulinemic hypoglycemia after enucleation of the mass. Therefore, the early genetic identification of MEN1 mutation is considerable for children with at least one manifestation.

MicroRNAs as novel biomarkers for the diagnosis and treatment of pediatric diseases.

MicroRNAs (miRNAs) are highly conserved noncoding RNAs that regulate gene expression by silencing or degrading messenger RNAs. Many of the approximately 2,500 miRNAs discovered in humans are known to regulate vital biological processes, including cell differentiation, proliferation, apoptosis, and embryonic tissue development. Aberrant miRNA expression may have pathological and malignant consequences. Therefore, miRNAs have emerged as novel diagnostic markers and potential therapeutic targets for various diseases. Children undergo various stages of growth, development, and maturation between birth and adulthood. It is important to study the role of miRNA expression in normal growth and disease development during these developmental stages. In this mini-review, we discuss the role of miRNAs as diagnostic and prognostic biomarkers in various pediatric diseases.

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula.

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals.

Positive Associations between Body Mass Index and Hematological Parameters, Including RBCs, WBCs, and Platelet Counts, in Korean Children and Adolescents.

We conducted this study to investigate the associations between hematological parameters and obesity in children and adolescents. The levels of hematological parameters (including white blood cells [WBCs], red blood cells [RBCs], hemoglobin [Hb], hematocrit [Hct], and platelets) of 7997 participants (4259 boys and 3738 girls) aged 10-18 years were recorded. The parameters were compared among participants with normal weight, overweight, and obesity. Significantly higher mean levels of WBCs (7.16 vs. 6.16 × 103/mm3, p < 0.001), RBCs (4.90 vs. 4.82 × 106/mm3, p < 0.001), Hb (14.07 vs. 13.99 g/dL, p < 0.05), Hct (42.31 vs. 41.91%, p < 0.001), and platelets (311.87 vs. 282.66 × 103/mm3, p < 0.001) were found in the obese than normal weight group, respectively, after adjusting for body mass index (BMI) and sex. BMI SDS had significant positive associations with the levels of WBCs (ß = 0.275, p < 0.001), RBCs (ß = 0.028, p < 0.001), Hb (ß = 0.034, p < 0.001), Hct (ß = 0.152, p < 0.001), and platelets (ß = 8.372, p < 0.001) after adjusting for age, sex, and socioeconomic factors in a multiple linear regression analysis. A higher BMI was associated with elevated WBC, RBC, Hb, Hct, and platelet counts in children and adolescents. Because higher levels of hematological parameters are potential risk factors for obesity-related diseases, hematological parameters should be evaluated in obese children and adolescents.

Exosomal miRNA Profile in Small-for-Gestational-Age Children: A Potential Biomarker for Catch-Up Growth.

Objective: The mechanism underlying postnatal growth failure and catch-up growth in small-for-gestational-age (SGA) children is poorly understood. This study investigated the exosomal miRNA signature associated with catch-up growth in SGA children. Methods: In total, 16 SGA and 10 appropriate-for-gestational-age (AGA) children were included. Serum exosomal miRNA was analyzed using next-generation sequencing (NGS). Exosomal miRNA was profiled for five SGA children with catch-up growth (SGA-CU), six SGA children without CU growth (SGA-nCU), and five AGA children. Results: Exosomal miRNA profiles were clustered into three clear groups. The exosomal miRNA expression profiles of the SGA-nCU group differed from those of the SGA-CU and AGA groups. In all, 22 miRNAs were differentially expressed between SGA-nCU and AGA, 19 between SGA-nCU and SGA-CU, and only 6 between SGA-CU and AGA. In both SGA-nCU and SGA-CU, miR-874-3p was upregulated and miR-6126 was downregulated. Therefore, these two miRNAs could serve as biomarkers for SGA. Compared with SGA-CU and AGA, miR-30c-5p, miR-363-3p, miR-29a-3p, and miR-29c-3p were upregulated in SGA-nCU, while miR-629-5p and miR-23a-5p were downregulated. These six miRNAs could be associated with growth failure in SGA-nCU children. Conclusions: SGA children without CU have a distinct exosomal miRNA expression profile compared with AGA and SGA children with CU. Exosomal miRNAs could serve as novel biomarkers for CU.

Hemoglobin and hematocrit levels are positively associated with blood pressure in children and adolescents 10 to 18 years old.

To investigate the associations between hemoglobin (Hb) concentration and hematocrit (Hct), and blood pressure (BP) in children and adolescents. The study population consisted of 7950 subjects total (4229 boys and 3721 girls) aged 10-18 years who participated in the Korea National Health and Nutrition Examination Surveys conducted between 2007 and 2017. The prevalence of hypertension was 19.19% (21.51% for boys and 16.5% for girls) among the study population, and the prevalence of obesity was 9.59% (10.5% for boys and 8.6% for girls). Hb count and Hct tended to increase with the degree of obesity and BP elevation. Systolic BP (SBP) and diastolic BP (DBP) positively correlated with Hb count and Hct in both sexes. Following multiple linear regression analysis, Hb count and Hct presented a positive association with SBP and DBP after adjusting for age, BMI SDS, alcohol consumption, smoking status, physical activity, rural residence, household income, diagnosis of T2DM, hypertension, and dyslipidemia. Hb count and Hct were positively associated with SBP and DBP in children and adolescents 10-18 years old.

Distribution of waist-to-height ratio and cardiometabolic risk in children and adolescents: a population-based study.

This study was performed to evaluate the waist-to-height ratio (WHtR) distribution and assess its relationship with cardiometabolic risk in children and adolescents. A total of 8091 subjects aged 10-18 years were included from a nationally representative survey. Participants were classified into three groups: (1) < 85th, (2) ≥ 85th and < 95th, and (3) ≥ 95th percentile of WHtR. The WHtR distribution varied with sex and age. Whereas WHtR decreased from age 10-15 years in boys and from age 10-12 years in girls, it slightly increased thereafter. Compared to the < 85th percentile group, the WHtR ≥ 85th and < 95th percentile group had an odds ratio (OR) of 1.2 for elevated blood pressure (BP), 1.89 for elevated triglycerides (TGs), 1.47 for reduced high-density lipoprotein cholesterol (HDL-C) and 4.82 for metabolic syndrome (MetS). The ≥ 95th percentile group had an OR of 1.4 for elevated BP, 2.54 for elevated glucose, 2.22 for elevated TGs, 1.74 for reduced HDL-C, and 9.45 for MetS compared to the < 85th percentile group. Our results suggest that sex- and age-specific WHtR percentiles can be used as a simple clinical measurement to estimate cardiometabolic risk.

Serum level of NPTX1 is independent of serum MKRN3 in central precocious puberty.

OBJECTIVES: Makorin ring finger protein 3 (MKRN3) is associated with the initiation of puberty, and loss of function mutation of MKRN3 is the most common genetic cause of central precocious puberty (CPP). A recent study reported that MKRN3 interacts with and suppresses neural pentraxin-1 precursor (NPTX1) activity via polyubiquitination during early puberty in the mouse hypothalamus. This study investigated the correlation between serum NPTX1 and MKRN3 in CPP girls and predicted the potential role of NPTX1 in pubertal progression. METHODS: In this case-control study, we examined 34 girls diagnosed with CPP and 34 healthy prepubertal girls. Anthropometric and hormonal parameters were measured and serum levels of NPTX1 and MKRN3 were evaluated with commercial enzyme-linked immunosorbent assay kits. RESULTS: Serum MKRN3 level decreased significantly in CPP patients compared to controls (344.48 ± 333.77 and 1295.21 ± 780.80 pg/mL, respectively, p<0.001). Serum MKRN3 tended to decrease as Tanner breast stage increased. However, no significant difference was observed in serum NPTX1 levels between patients and controls (20.14 ± 31.75 ng/mL and 12.93 ± 8.28 ng/mL, respectively, p=0.248). The serum level of NPTX1 did not change significantly with the Tanner breast stage. Serum NPTX1 was correlated with the height standard deviation score (r=0.255; p<0.05), but was not correlated with serum MKRN3 level or the others. Conclusion: Although serum NPTX1 level was independent of serum MKRN3 level, the possibility they might be involved in the progression of puberty or CPP remains. Further research is needed to determine their role in the hypothalamus.

Spontaneous Sexual Development and Heavy Menstrual Bleeding in 45,X Monosomy and 45,X/47,XXX Mosaic Turner Syndrome and a Review of the Literature.

Turner syndrome (TS) is one of the most common sex chromosome disorders and is characterized by short stature and gonadal dysgenesis. A few patients with TS achieve normal sexual development, menarche, and even pregnancy. We encountered two cases of Turner syndrome with spontaneous sexual development and menstruation. The patients had different karyotypes, 45,X monosomy and 45,X/47,XXX mosaic TS, and presented with severe anemia due to excessive menstrual bleeding. Abnormal uterine bleeding patterns are expected in patients with primary ovarian insufficiency; however, the menstrual patterns of patients with TS have not been well described in the literature. Here, we describe these cases along with a brief review of the relevant literature.

Body mass index trajectories and adiposity rebound during the first 6 years in Korean children: Based on the National Health Information Database, 2008-2015.

PURPOSE: We analyzed the nationwide longitudinal data to explore body mass index (BMI) growth trajectories and the time of adiposity rebound (AR). METHODS: Personal data of 84,005 subjects born between 2008 and 2012 were obtained from infant health check-ups which were performed at 5, 11, 21, 33, 45, 57, and 69 months. BMI trajectories of each subject were made according to sex and the timing of AR, which was defined as the lowest BMI occurred. Subjects were divided according to birth weight and AR timing as follows: very low birth weight (VLBW), 0.5 kg ≤ Bwt ≤ 1.5 kg; low birth weight (LBW), 1.5 kg < Bwt ≤ 2.5 kg; non-LBW, 2.5 kg < Bwt ≤ 5.0 kg; very early AR, before 45 months; early AR, at 57 months; and moderate-to-late AR, not until 69 months. MAIN RESULTS: Median time point of minimum BMI was 45 months, and the prevalence rates of very early, early, and moderate-to-late AR were 63.0%, 16.6%, and 20.4%, respectively. BMI at the age of 57 months showed a strong correlation with AR timing after controlling for birth weight (P < 0.001). Sugar-sweetened beverage intake at 21 months (P = 0.02) and no-exercise habit at 57 months (P < 0.001) showed correlations with early AR. When VLBW and LBW subjects were analyzed, BMI at 57 months and breastfeeding at 11 months were correlated with rapid weight gain during the first 5 months (both P < 0.001). CONCLUSIONS: Based on this first longitudinal study, the majority of children showed AR before 57 months and the degree of obesity at the age of 57 months had a close correlation with early AR or rapid weight gain during infancy.

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty.

BACKGROUND: Luteinizing hormone (LH) is a useful parameter in diagnosing precocious puberty. The pubertal response of serum LH to a GnRH stimulation test is varied, and clinical symptoms of precocious puberty are sometimes disproportionate with serum LH concentrations. Many patients present in a state of precocious puberty that advances rapidly, but the post-GnRH peak LH remains prepubertal. LH receptor mutations are suspected of involvement in the non-classic type of central precocious puberty (CPP). OBJECTIVE: To examine the association between LHCGR polymorphism and non-classic CPP in subjects exhibiting a peak LH<5 IU/L on a GnRH stimulation test. METHODS: In total, 102 girls with non-classic CPP and 100 normal adult women were enrolled. All subjects underwent LHCGR gene analysis by the Sanger method, and patients and controls were compared. Auxological data and gonadotropin concentrations were analyzed in the 102 patients. Of these patients, 75 completed GnRH agonist treatment, and the treatment outcomes were analyzed. RESULTS: A total of seven variants were identified, including two missense mutations (g.48698754 G/A and g.48688613 G/A) that were found in the patient group (no patients contained both mutations). In silico analysis of these missense mutations suggested the possibility of damaging the LHCGR. However, no significant association was found between the identified LHCGR variants and non-classic CPP. GnRH agonist treatment decreased bone age advancement and increased predicted adult height. CONCLUSIONS: LHCGR gene polymorphisms do not appear to be a major causative factor for the relatively low concentration of LH in patients with non-classic CPP. GnRH agonist treatment improved clinical parameters in these patients.

Factors affecting bone age maturation during 3 years of growth hormone treatment in patients with idiopathic growth hormone deficiency and idiopathic short stature: Analysis of data from the LG growth study.

To investigate the progression rate of bone age (BA) and associated factors during the first 3 years of growth hormone (GH) treatment in children with idiopathic GH deficiency (iGHD) and idiopathic short stature (ISS).Data for prepubertal children with iGHD and ISS who were treated with recombinant human GH were obtained from the LG Growth Study Database and analyzed. Height, weight, BA, insulin-like growth factor-1 (IGF-1) level, and GH dose were recorded every 6 months. Differences between BA and chronological age (CA), BA-CA, were calculated at each measurement. This study included 92 (78 iGHD and 14 ISS) subjects.After 3 years of GH treatment, the height z-score was -1.09 ±â€Š0.71 (P < .001 compared to baseline), BA-CA was -1.21 ±â€Š1.18 years (P < .001), and IGF-1 standard deviation score (SDS) was 0.43 ±â€Š1.21 (P < .001) in the iGHD subjects; the change in BA over the 3 years was 3.68 ±â€Š1.27 years. In the ISS subjects, the height z-score was -1.06 ±â€Š0.59 (P < .001), BA-CA was -0.98 ±â€Š1.23 years (P = .009), and IGF-1 SDS was 0.16 ±â€Š0.76 (P = .648); the change in BA over the 3 years was 3.88 ±â€Š1.36 years. The only significant factor associated with the BA progression was the BA-CA at 1 year of GH treatment (OR = 2.732, P = .001). The baseline BA-CA, IGF-1 SDS, and GH dose did not influence BA progression.Prepubertal subjects with iGHD and ISS showed height improvement and mild BA acceleration over the first 3 years of GH treatment. However, because the BA progression rate was considered to be clinically acceptable, GH treatment may increase the predicted adult height during this period.

Makorin ring finger 3 gene analysis in Koreans with familial precocious puberty.

BACKGROUND: Precocious puberty is known as an idiopathic, sporadic disease. Recently, specific mutations have been shown to cause familial central precocious puberty (CPP). The makorin ring finger 3 (MKRN3) gene plays a key role in puberty; loss-of-function mutations in the gene trigger familial CPP. To date, most described patients have been Western; few Asians with CPP have been documented. OBJECTIVE: To identify MKRN3 gene mutations or polymorphisms in Korean patients with familial CPP. METHODS: 26 patients with CPP and their parents (total 13 families) were recruited. We measured endocrine and auxological parameters, and sequenced all MKRN3 exons. RESULTS: We found no MKRN3 mutations. Two MKRN3 exon polymorphisms were identified. The g.23566445 C/T polymorphism was found in eight families; a novel single nucleotide polymorphism (SNP) g.23567001 A/C was found in one family. These variants are synonymous SNPs; their functional roles remain unknown. CONCLUSIONS: MKRN3 mutation is uncommon in Korean patients with familial CPP. Ethnic variation in the MKRN3 mutational status is thus evident.

Association of the urinary sodium to urinary specific gravity ratio with metabolic syndrome in Korean children and adolescents: The Korea National Health and Nutrition Examination Survey 2010-2013.

OBJECTIVES: This study aimed to evaluate the association between sodium intake and metabolic syndrome (MetS) in Korean boys. METHODS: A total of 1,738 boys aged 10-18 years were included in this study from the Korea National Health and Nutrition Examination Survey (KNHANES) during the years 2010-2013. Sodium intake was assessed using the urinary sodium excretion to urinary specific gravity ratio (U-Na to U-SG ratio). RESULTS: The median U-Na to U-SG ratio was 133.27 mmol/L (interquartile range: 95.66-178.50 mmol/L). Significant positive associations were found between the U-Na to U-SG ratio and the TG (P = 0.001 for trend) and TG concentrations, and these concentrations were significantly higher in boys with a U-Na to U-SG ratio in the highest quartile compared with those with a ratio in the lowest (P = 0.001) and second (P = 0.033) quartiles, as demonstrated through analysis of covariance (ANCOVA) after adjustment for possible confounders, including age, BMI standard deviation score, ferritin, vitamin D, house income, smoking, alcohol intake, physical activity, season, total intake, total energy intake, protein intake, fat intake, carbohydrate intake, and water intake. Significant inverse associations were found for the U-Na to U-SG ratio with the HDL-C (P = 0.033 for trend) and HDL-C levels, and these values were significantly lower in boys with a ratio in the highest quartile compared with those with a ratio in the second quartile (P = 0.020), as demonstrated through an ANCOVA. Although the trends did not reach statistical significance, a higher U-Na to U-SG ratio tended to be associated with higher SBP (P = 0.086 for trend), DBP (P = 0.063 for trend), and glucose levels (P = 0.099 for trend), as illustrated through ANCOVA. Boys with a ratio in the highest quartile exhibited a 1.73-fold increased risk for elevated TG (95% CI, 1.19-2.51) and a 2.66-fold increased risk for MetS (95% CI, 1.11-6.35) compared with those with a ratio in the lowest quartile, as demonstrated through multivariate logistic regression analyses after adjusting for confounders. CONCLUSIONS: Our results suggest that high sodium intake may be significantly independently associated with MetS in Korean boys aged 10-18 years.