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High lipoprotein(a) [Lp(a)] levels are associated with increased risk of cardiovascular disease. However, the association between Lp(a) and fatty liver disease (FLD) remains controversial. Therefore, we analyzed the relationship between FLD and serum Lp(a) levels in Korean adults.A total of 22,534 participants who underwent a routine health screening program at Kangbuk Samsung Hospital in 2010 and 2014 were enrolled. Anthropometric and biochemical parameters, including Lp(a), were measured. The presence of FLD was assessed using abdominal ultrasonography. Odds ratios (ORs) for the presence of FLD were analyzed in quartile groups of serum Lp(a) levels using logistic regression. We divided the participants into four groups according to the median values of Lp(a) and homeostasis model assessment for insulin resistance (HOMA-IR).Among the total study population, 3030 (13.4%) participants had fatty liver disease. The mean Lp(a) level was lower in subjects with FLD than in those without (70.0 vs 73.8 nmol/L, p 0.001). The OR for FLD was the lowest in the fourth Lp(a) quartile group, using the first quartile group as the reference group after adjusting for confounding factors [0.815; 95% confidence interval (CI) 0.725-0.916]. When the OR for FLD was analyzed in four groups divided by the median values of Lp(a) and HOMA-IR, the low Lp(a)-high HOMA-IR group had the greatest OR for FLD, using the high Lp(a)-low HOMA-IR group as the reference (1.903; 95% CI 1.679-2.158).Serum Lp(a) levels were inversely associated with the presence of FLD. Subjects with low Lp(a) and high insulin resistance (IR) showed higher risk of FLD than those with high Lp(a) and low IR, suggesting the opposite associations of Lp(a) and IR with FLD.

Background It is well known that high serum ferritin, a marker of iron storage, predicts incident type 2 diabetes. Limited information is available on the association between transferrin, another marker of iron metabolism, and type 2 diabetes. Thus, we investigated the association between transferrin and incident type 2 diabetes. Methods Total 31,717 participants (mean age, 40.4±7.2 years) in a health screening program in 2005 were assessed via cross-sectional analysis. We included 30,699 subjects who underwent medical check-up in 2005 and 2009 and did not have type 2 diabetes at baseline in this retrospective longitudinal analysis. Results The serum transferrin level was higher in the type 2 diabetes group than in the non-type 2 diabetes group (58.32±7.74 μmol/L vs. 56.17±7.96 μmol/L, Pl0.001). Transferrin correlated with fasting serum glucose and glycosylated hemoglobin in the correlational analysis (r=0.062, Pl0.001 and r=0.077, Pl0.001, respectively) after full adjustment for covariates. Transferrin was more closely related to homeostasis model assessment of insulin resistance than to homeostasis model assessment of β cell function (r=0.042, Pl0.001 and r=-0.019, P=0.004, respectively) after full adjustment. Transferrin predicted incident type 2 diabetes in non-type 2 diabetic subjects in a multivariate linear regression analysis; the odds ratio (95% confidence interval [CI]) of the 3rd tertile compared to that in the 1st tertile of transferrin for incident diabetes was 1.319 (95% CI, 1.082 to 1.607) after full adjustment (P=0.006). Conclusion Transferrin is positively associated with incident type 2 diabetes in Koreans.

BackgroundAlthough autonomic imbalance is associated with an increased risk for metabolic disease, its effects on nonalcoholic fatty liver disease (NAFLD) remains unclear. We aimed to evaluate whether autonomic dysfunction predicts the risk for nonalcoholic fatty liver disease (NAFLD).MethodsA total of 33,899 participants without NAFLD who underwent health screening programs between 2011 and 2018 were enrolled. NAFLD was identified by ultrasonography. Autonomic activity was estimated using heart rate variability (HRV). Time domain [standard deviation of the normal-to-normal interval (SDNN) and root mean square difference (RMSSD)]; frequency domain [total power (TP), low frequency (LF), and high frequency (HF), and LF/HF ratio were analyzed.FindingsA total 6,466 participants developed NAFLD within a median of 5.7 years. Subjects with incident NAFLD showed decreased overall autonomic modulation and vagal activity with lowered SDNN, RMSSD, HF, normalized HF, compared to those without NAFLD. As the SDNN, RMSSD, TP, LF, and HF tertiles increased, the risk of NAFLD decreased with tertile 1 being the reference group [the hazard ratios (95% confidence intervals) of tertile 3 were 0.90 (0.85–0.96), 0.83 (0.78–0.88), 0.91 (0.86-0.97), 0.93 (0.87-0.99) and 0.89 (0.83-0.94), respectively] after adjusting for potential confounders. The risk for NAFLD was significantly higher in subjects in whom sustained elevated heart rate, normalized LF, and LF/HF ratio values than in those with sustained decrease in these parameters during follow-up.ConclusionsOverall autonomic imbalance, decreased parasympathetic activity, and recently increased sympathetic activity might increase the risk of NAFLD.

Background To confirm the accuracy of transcutaneous bilirubin (TcB) in the neonatal intensive care unit both with and without phototherapy, and compare forehead and sternum as the TcB assessment site. Methods We simultaneously assessed the total serum bilirubin (TSB) and TcB at the forehead and sternum, using a JM-103 bilirubinometer. We analyzed the correlation between the TSB and TcB assessed at the forehead and sternum, with measurements classified as ‘without phototherapy’ (before phototherapy and > 24 hours after phototherapy discontinuation) and ‘with phototherapy’ (after 24 hours of phototherapy). Results There were 1,084 paired forehead and sternum TcB measurements, with the corresponding TSB measurement, from 384 infants. Their mean gestational age of 35.4 ± 3.2 weeks (62% were preterm) and a mean birth weight of 2434 ± 768 grams, and TSB was 6.61 ± 3.56 mg/dL. Without phototherapy, TcB values at the forehead and sternum were correlated well to the TSB value (r = 0.925 and 0.915, respectively). With phototherapy, TcB values at the forehead and sternum were significantly correlated with the TSB value, but TcB at the forehead (r = 0.751) was a better match to the TSB than was TcB at the sternum (r = 0.668). Additionally, Bland-Altman plots showed a greater degree of underestimation of the TSB by TcB at the sternum with phototherapy. Conclusions TcB was more accurate in infants not receiving phototherapy. During phototherapy, it is better to assess TcB at the forehead rather than at the sternum.

Objective Thyroid hormones play crucial roles in the control of energy homoeostasis and can influence body composition. In contrast, the changes in body composition might influence thyroid hormone levels. We evaluated associations between thyroid hormone levels, body composition and insulin resistance in euthyroid subjects with normal thyroid ultrasound (US) findings. Design and patients This retrospective cross-sectional study included 36 655 euthyroid subjects who joined the medical health check-up programme at our institution. Serum thyroid hormone levels were analysed in association with body fat percentage (BFP), skeletal muscle mass index (SMI) and homoeostatic model assessment of insulin resistance (HOMA-IR). Linear regression analyses were performed to evaluate relationships between thyroid hormone levels and anthropometric parameters. Results Mean age was 36.4 years, and 49% of subjects were female. In multiple linear regression analysis, serum-free triiodothyronine (FT3) levels exhibited positive associations with waist circumference (WC) and HOMA-IR and a negative association with body weight, body mass index (BMI) and SMI among both men and women. The association between serum-free thyroxine (FT4) levels and anthropometric markers showed inconsistent results in men and women. Serum thyroid-stimulating hormone (TSH) levels showed a positive association with HOMA-IR in both men and women. Conclusions Lower SMI was significantly associated with higher serum FT3 levels, the active form of thyroid hormone, in both men and women. Higher insulin resistance was positively associated with serum FT3 levels and inversely associated with serum TSH levels in euthyroid subjects with normal thyroid US findings.

Purpose Rotavirus infection has recently been reported to be associated with seizures accompanied by leukoencephalopathy in newborns. We aimed to determine long-term outcomes and prognostic factors in newborns with neonatal seizures caused by rotavirus-associated leukoencephalopathy. Methods We retrospectively reviewed the records and brain magnetic resonance (MR) images of 32 patients who fulfilled the following criteria: (1) neonatal seizures, (2) distinctive symmetric cerebral white matter lesions on diffusion-weighted MR images (DWI), (3) rotavirus infection, (4) absence of a specific etiology of seizures, except for the aforementioned DWI lesions, and (5) Korean Bayley Scales of Infant Development II (K-BSID-II) assessment after 12 months of age. Results The mean age at seizure onset was 4.7 ± 0.8 days. The median age of the patients at the time of K-BSID-II assessment was 22 months. Fourteen patients (43.8%) showed normal or accelerated performance in the mental and motor scales, while 18 patients (56.2%) had delayed performance in the mental and/or motor scales. Seven patients (21.9%) had significantly delayed performances on the mental and/or motor scales. The percentage of volume of diffusion-restricted lesions based on total brain volume was significantly negatively correlated with the mental developmental index (MDI) score ( r = −0.507, p = .003), but not with the psychomotor developmental index (PDI) score ( r = −0.324, p = .071). Conclusions Rotavirus-associated leukoencephalopathy in newborns around 5 days of age can cause adverse neurodevelopmental outcomes with a wide range of severity. The extent of white matter lesion on initial DWI can predict neurocognitive outcome.

Background and Aim Previous studies reported that many patients are at high risk for cardiovascular disease (CVD) despite achieving recommended low-density lipoprotein cholesterol (LDL-C) levels. Therefore, we investigated whether the association between LDL-C and the risk for incident CVD differed according to high-density lipoprotein cholesterol (HDL-C) levels using coronary artery calcium score (CACS) progression as a surrogate marker for predicting CVD. Methods We investigated 2132 Korean men in a health screening program, in which CACS was measured at baseline and after 4 years. Coronary artery calcification (CAC) progression was defined as a change in CACS ≥0 over 4 years. We divided the subjects into nine groups according to baseline HDL-C and LDL-C levels and compared their risks for CAC progression. Results After 4 years, 475 subjects (22.3%) exhibited CAC progression. We identified a positive relationship between baseline LDL-C levels and the risk for incident CAC. However, this association was attenuated by high baseline HDL-C levels. Multivariate logistic regression analysis adjusted for age, body mass index, systolic blood pressure, fasting glucose, smoking, and exercise status revealed that the odds ratios for incident CAC in the lowest HDL-C tertile were 3.08 for LDL-C tertile 3 and 2.02 for LDL-C tertile 2 compared to LDL-C tertile 1. However, these differences disappeared in the highest HDL-C tertile (HDL-C ≥54.0 mg/dL). Conclusions In this longitudinal study, we found that the positive relationship between LDL-C and the relative risk for incident CAC was attenuated by higher HDL-C levels. Therefore, HDL-C levels should be considered when estimating CVD risk.

Purpose Insulin resistance is one of the most important mechanisms in the development of diabetes, and it is closely related to the presence and severity of coronary heart disease. Triglyceride glucose (TyG) index is a useful marker of insulin resistance; however, few studies have investigated the relationship between TyG and subclinical atherosclerosis. Therefore, we evaluated the association of TyG and subclinical coronary atherosclerosis as measured by coronary artery calcium score (CACS). Methods Our study included 30,776 participants (mean age of 41 years, 80.4% male) enrolled in a health screening program, in whom CACS were measured. Homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-body mass index (BMI), and TyG-waist circumference (WC) were subsequently analyzed. Indices were calculated using the following formulae: HOMA-IR=fasting insulin (μU/mL)×fasting plasma glucose (FPG; mmol/L)/22.5; TyG index=Ln [TG (mg/dL)×FPG (mg/dL)/2]; TyG-BMI=TyG index×BMI; and TyG-WC=TyG index×WC. CACS was measured using multidetector computed tomography, and the presence of coronary artery calcification (CAC) was defined by CACS>0. Results The prevalence of CAC was 14.4% in the study population. Multivariate logistic regression analysis showed that participants with TyG-BMI in the highest tertile were 1.638 times more likely to have CAC after adjustment for other metabolic parameters compared with participants with TyG-BMI in the lowest tertile (odds ratio, 1.612; 95% confidence interval, 1.465 to 1.774). The receiver operating characteristics curve for prediction of CAC showed that TyG-WC index had a higher area under the curve (AUC=0.626) than other indices (AUCTyG=0.617, AUCTyG-BMI=0.616, AUCHOMA-IR=0.562). Conclusion TyG index predicted CAC better than other markers of insulin resistance, and could be a useful marker for predicting subclinical atherosclerosis.

s: Congenital paraesophageal hiatal hernia (CPEH) is a rare condition. CPEH can cause important clinical problems such as gastric volvulus, hematemesis, vomiting, failure to thrive, and respiratory distress, it requires early diagnosis and prompt surgical treatment. In this paper, we describe a case of CPEH that was suspected in a prenatal ultrasound. Postnatal upper gastrointestinal contrast series confirmed a CPEH with intrathoracic gastric volvulus. An emergency operation was performed. The stomach was reduced, the hiatal defect was repaired by crural approximation, and a Nissen fundoplication was done. The prenatal diagnosis of CPEH is unusual, but prenatal detection is important because it allows planned neonatal surgery before the onset of complications and reduces long-term morbidity. Keywords: Congenital paraesophageal hiatal hernia, Antenatal diagnosis, Gastric volvulus

Background The main aim of this study was to estimate the effectiveness of routine scrubbing by change of the incidence of central line-associated bloodstream infections (CLABSI). Methods We surveyed cultures from the NICU environment in December 2017. We found that areas close to infants harbored more bacteria. We implemented routine scrubbing to control sites with the most bacteria starting from January 2018. We retrospectively reviewed and compared the data between the pre (2017) and post (2018) intervention periods. Results A total of 916 infants were included; 10 CLABSI episodes were identified, 9 and 1 episodes in the pre- and postintervention periods, respectively. We found that the incidence of CLABSI decreased significantly among all admitted infants (P = .006) and also among very low birth weight infants (P = .085). The number of CLABSI cases per 1,000 central line days decreased from 1.89 in 2017 to 0.23 in 2018 (P = .018). The most common bacterial species found in the cultures established from the NICU environment were identical to the CLABSI-causing coagulase-negative Staphylococcus. Conclusions Routine scrubbing significantly reduced CLABSI in the NICU.

OBJECTIVE The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians. RESEARCH DESIGN AND METHODS A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal intervals [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group. RESULTS During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70–0.95], 0.76 [0.65–0.90], and 0.78 [0.67–0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21–1.65], 1.32 [1.13–1.53], and 1.31 [1.13–1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance. CONCLUSIONS Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.

Background We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults. Methods Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: 25 kg/m2 (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0. Results When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]). Conclusion Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.

Results from previous studies support the association of lipoprotein(a) [Lp(a)] levels and coronary artery disease risk. In this study, we analyzed the association between baseline Lp(a) levels and future progression of coronary artery calcification (CAC) in apparently healthy Korean adults.A total of 2611 participants (mean age: 41years, 92% mend) who underwent a routine health check-up in 2010 and 2014 were enrolled. Coronary artery calcium score (CACS) were measured by multi-detector computed tomography. Baseline Lp(a) was measured by high-sensitivity immunoturbidimetric assay. Progression of CAC was defined as a change in CACS0 over four years.Bivariate correlation analyses with baseline Lp(a) and other metabolic parameters revealed age, total cholesterol, HDL-C, LDL-C and CACS to have a significant positive correlation, while body weight, fasting glucose level, blood pressure and triglyceride level were negatively correlated with baseline Lp(a) level. After four years of follow-up, 635 subjects (24.3%) had CAC progression. The participants who had CAC progression were older, composed of more men, more obese, and had higher fasting glucose levels and worse baseline lipid profiles compared to those who did not have CAC progression. The mean serum Lp(a) level was significantly higher in subjects who had CAC progression compared to those who did not (32.5 vs. 28.9mg/dL, p0.01). When the risk for CAC progression according to baseline Lp(a) was calculated, those with Lp(a) level≥50mg/dL had an odds ratio of 1.333 (95% CI 1.027-1.730) for CAC progression compared to those with Lp(a)50mg/dL after adjusting for confounding factors.In this study, the subjects who had higher Lp(a) were at significantly higher risk for CAC progression after four years of follow-up, suggesting the role of high Lp(a) in CAC progression.

Background The purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP) III and the American College of Cardiology (ACC)/American Heart Association (AHA) guidelines in Korean adults. Methods Renal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR): stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR

Background Diabetes can be efficiently prevented by life style modification and medical therapy. So, identification for high risk subjects for incident type 2 diabetes is important. The aim of this study is to identify the best β-cell function index to identify high risk subjects in non-diabetic Koreans. Methods This is a retrospective longitudinal study. Total 140 non-diabetic subjects who underwent standard 2-hour 75 g oral glucose tolerance test from January 2007 to February 2007 at Kangbuk Samsung Hospital and followed up for more than 1 year were analyzed (mean follow-up, 54.9±16.4 months). The subjects were consist of subjects with normal glucose tolerance (n=44) and subjects with prediabetes (n=97) who were 20 years of age or older. Samples for insulin and C-peptide levels were obtained at 0 and 30 minutes at baseline. Results Thirty subjects out of 140 subjects (21.4%) developed type 2 diabetes. When insulin-based index and C-peptide-based index are compared between progressor and non-progressor to diabetes, all C-peptide-based indices were statistically different between two groups, but only insulinogenic index and disposition index among insulin-based index were statistically different. C-peptide-based index had higher value of area under receiver operating characteristic curve (AROC) value than that of insulin-based index. "C-peptidogenic" index had highest AROC value among indices (AROC, 0.850; 95% confidence interval, 0.761 to 0.915). C-peptidogenic index had significantly higher AROC than insulinogenic index (0.850 vs. 0.731 respectively; P=0.014). Conclusion C-peptide-based index was more closely related to incident type 2 diabetes in non-diabetic subjects than insulin-based index.

The visceral adiposity index (VAI) is a mathematical tool that reflects a patient's visceral adiposity and insulin resistance. Recent studies have noted an association between VAI and cardiovascular event. We analyzed the association between VAI and coronary artery calcium score (CACS) in Korean adults.For 33,468 participants (mean age 42 yrs) in a health screening program, VAI was calculated using the following formulae: [waist circumference (WC)/{39.68 + (1.88 * body mass index (BMI))}] * (triglyceride/1.03) * {1.31/high-density lipoprotein cholesterol (HDL-C)} for men and [WC/{36.58 + (1.89 * BMI)}] * (triglyceride/0.81) * (1.52/HDL-C) for women. Coronary artery calcium scores were measured with multi-detector computed tomography.CACS was positively correlated with VAI (r = 0.027, p 0.001). Subjects with 0 CACS100 and CACS ≥ 100 had significantly higher VAI compared to those with CACS = 0 (2.04 ± 1.97, 2.08 ± 1.67 vs. 1.68 ± 1.50, p 0.001). In logistic regression analyses with CACS0 as the dependent variable, subjects in the highest tertile of VAI (1.777) had significantly increased odds ratio for CACS0 compared to subjects in the lowest tertile (0.967), even after adjusting for confounding variables, including BMI (OR 1.26, 95% CI 1.147-1.381).Subjects with high VAI had increased risk for subclinical atherosclerosis, as assessed by CACS. Key messages Recent studies have noted an association between visceral adiposity index (VAI) and cardiovascular event. Subjects with coronary artery calcification (CAC) showed significantly higher VAI compared to those without CAC. The subjects with high VAI showed increased odds ratio for CAC as compared to subjects with low VAI, suggesting high VAI reflects increased risk for subclinical atherosclerosis.

Background Waist-to-height ratio (WHtR) is an easy and inexpensive adiposity index that reflects central obesity. In this study, we examined the association of various baseline adiposity indices, including WHtR, with the development of diabetes over 4 years of follow-up in apparently healthy Korean individuals. Methods A total of 2,900 nondiabetic participants (mean age, 44.3 years; 2,078 men) in a health screening program, who repeated the medical check-up in 2005 and 2009, were recruited. Subjects were divided into two groups according to development of diabetes after 4 years. The cut-off values of baseline body mass index (BMI), waist circumference (WC), and WHtR for the development of diabetes over 4 years were calculated. The sensitivity, specificity, and mean area under the receiver operator characteristic curve (AUROC) of each index were assessed. The odds ratio (OR) for diabetes development was analyzed for each of the three baseline adiposity indices. Results During the follow-up period, 101 new cases (3.5%) of diabetes were diagnosed. The cut-off WHtR value for diabetes development was 0.51. Moreover, WHtR had the highest AUROC value for diabetes development among the three adiposity indices (0.716, 95% confidence interval [CI], 0.669 to 0.763; 0.702, 95% CI, 0.655 to 0.750 for WC; 0.700, 95% CI, 0.651 to 0.750 for BMI). After adjusting for confounding variables, the ORs of WHtR and WC for diabetes development were 1.95 (95% CI, 1.14 to 3.34) and 1.96 (95% CI, 1.10 to 3.49), respectively. No significant differences were observed between the two groups regarding BMI. Conclusion Increased baseline WHtR and WC correlated with the development of diabetes after 4 years. WHtR might be a useful screening measurement to identify individuals at high risk for diabetes.

No cohort studies have evaluated the effect of obesity on the incidence of thyroid cancer according to metabolic health status. Therefore, this study examined the association of body mass index (BMI) and metabolic health status with thyroid cancer risk.A cohort study was performed involving 255,051 metabolically healthy (MH) and metabolically unhealthy (MUH) adults free of thyroid cancer at baseline who were followed for a median of 5.3 years. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and confidence interval (CI).During 1,402,426.3 person-years of follow-up, 2927 incident thyroid cancers were identified. Among men, the multivariable aHR for thyroid cancer comparing obesity, defined as a BMI ≥25 kg/mIn both MH and MUH men, obesity was associated with an increased risk of incident thyroid cancer, indicating excessive adiposity per se as an independent risk factor for thyroid cancer. Conversely, women with MUH obesity but not MH obesity were found to have an increased risk of thyroid cancer, indicating that obesity with accompanying metabolic abnormalities may affect thyroid cancer risk in women.

Objective Coronary artery calcification (CAC) is considered a surrogate marker for atherosclerotic burden. The aim of this study was to analyze the risk of incident CAC associated with diabetes development in non-diabetic subjects with zero CAC score (CACS) at baseline. Methods 2076 non-diabetic participants (mean age 40 years) in a health screening program in whom CACS were repeatedly measured by multi-detector computed tomography in four years of intervals and with zero CACS at baseline, were retrospectively analyzed. Glycemic status was assessed in both years, with subjects divided into three groups: subjects with ‘no progression’, ‘normal to impaired fasting glucose (IFG)’ and ‘progression to diabetes’. Insulin resistance was assessed by homeostasis model assessment-insulin resistance (HOMA-IR) index. Results Over 4 years, 204 subjects (9.8%) developed CAC. Subjects who developed diabetes showed the highest proportion of subjects with incident CAC among the three groups (21.0% vs. 9.3 and 10.4% in non-progressors and subjects from normal to IFG). The subjects with HOMA-IR level in higher half at baseline showed significantly increased risk for incident CAC in subjects who progressed from normal to IFG and in subjects who developed diabetes (1.740; 95% CI 1.014–2.985, 2.449; 95% CI 1.159–5.174) even after adjustment for confounding variables, whereas subjects with HOMA-IR level in lower half at baseline showed no significantly increased risk for incident CAC even in subjects who developed diabetes. Conclusions In this non-diabetic population, we found that increased risk for incident CAC in relation to diabetes development over 4 years was pronounced only in subjects with insulin resistance at baseline.

Background Hypertriglyceridemic waist phenotype is a simple screening parameter to identify people at increased risk for cardiovascular disease. We evaluated whether hypertriglyceridemic waist (HTGW) phenotype increases the risk for coronary artery calcification (CAC) in apparently healthy Korean adults. Methods A total of 32,186 participants (mean age 41.3, 80.2% men) in a health screening program, in whom the coronary artery calcium score (CACS) was measured, were analyzed. Subjects were divided into four groups: 1) normal waist circumference (WC)–normal triglyceride (TG) (NWNT), 2) normal WC–high TG (NWHT), 3) enlarged WC–normal TG (EWNT), and 4) enlarged WC–high TG (EWHT). Enlarged WC was defined as WC ≥90cm for men and ≥85cm for women; high serum TG was defined as TG ≥150mg/dL. The presence of CAC was defined by CACS >0, and CACS was analyzed in a logarithmized form of CACS plus 1 {ln(CACS+1)}. Results A total of 14.9% of the participants had CAC. The EWHT group showed the highest mean value for ln(CACS+1) among the four groups. The EWHT group showed the highest odds ratio for CAC, with NWHT group the second, and with EWNT group the third compared with the NWNT group after adjusting for confounding variables (1.579, 1.302, and 1.266 vs. NWNT). Conclusions The EWHT group showed the highest association for CAC, suggesting this HTGW phenotype as a useful marker for the detection of subjects with high cardiometabolic risk in healthy Korean adults.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Background: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. Methods: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. Results: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositolrequiring kinase 1α, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. Conclusion: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.

Objective Ezetimibe is known as a Niemann-Pick C1-Like 1 (NPC1L1) inhibitor and has been used as an agent for hypercholesterolemia. In our previous study, ezetimibe administration improved glycemic control and increased glucagon like peptide-1 (GLP-1), an incretin hormone with anti-diabetic properties. However, the mechanisms by which ezetimibe stimulates GLP-1 secretion are not fully understood. Thus, the specific aim of this study was to investigate the mechanism(s) by which ezetimibe stimulates GLP-1 secretion. Materials/methods Male KK/H1J mice were divided into following groups: AIN-93G (NC), NC with ezetimibe (10mg/kg/day), 45% high fat (HF) diet, and HF diet with ezetimibe. To investigate the role of ezetimibe in glucose homeostasis and GLP-1 secretion, an insulin tolerance test was performed and serum and intestinal GLP-1 levels and intestinal mRNA expression involved in GLP-1 synthesis were measured after 6weeks of ezetimibe treatment. In vivo and in vitro dipeptidyl peptidase-4 (DPP-4) inhibition assays were employed to demonstrate the association between ezetimibe-induced GLP-1 change and DPP-4. The molecular mechanism by which ezetimibe affects GLP-1 secretion was evaluated by using human enteroendocrine NCI-H716 cells. Results Ezetimibe supplementation significantly ameliorated HF-increased glucose and insulin resistance in the type 2 diabetic KK/H1J mouse model. Serum and intestinal active GLP-1 levels were significantly increased by ezetimibe in HF-fed animals. However, mRNA expression of genes involved in intestinal GLP-1 synthesis was not altered. Furthermore, ezetimibe did not inhibit the activity of either in vivo or in vitro dipeptidyl peptidase-4 (DPP-4). The direct effects of ezetimibe on GLP-1 secretion and L cell secretory mechanisms were examined in human NCI-H716 intestinal cells. Ezetimibe significantly stimulated active GLP-1 secretion, which was accompanied by the activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK). Ezetimibe-increased GLP-1 secretion was abrogated by inhibiting the MEK/ERK pathway with PD98059. Conclusion These findings suggest a possible novel biological role of ezetimibe in glycemic control to stimulate intestinal GLP-1 secretion via the MEK/ERK signaling pathway.

PURPOSE Anogential distance (AGD) and the 2:4 digit length ratio appear to provide a reliable guide to fetal androgen exposure. We intended to investigate the current status of penile size and the relationship between penile length and AGD or digit length according to birth weight in Korean newborn infants. MATERIALS AND METHODS Between May 2013 and February 2014, among a total of 78 newborn male infants, 55 infants were prospectively included in this study. Newborn male infants with a gestational age of 38 to 42 weeks and birth weight>2.5 kg were assigned to the NW group (n=24) and those with a gestational age

Objective: We aimed to establish the reference range of gamma glutamyl transferase (GGT) in the first week of life at each gestational age (GA).Methods: This retrospective study included infants born and admitted before 7 days of age with no apparent congenital liver disease during four consecutive years. Early GGT levels measured at 3–7 days of age were analyzed according to GA. Differences according to sex, mode of delivery, small for gestational age, and the predictability for cholestasis were analyzed.Results: We analyzed early GGT values in 2091 neonates. The average reference value in neonates (156.7 ± 98.2 IU/L) was much higher than that in adults. The GGT values were significantly higher in preterm than in term infants and in male infants than in female infants. Mode of delivery and small for gestational age were not significantly related to GGT level. Early GGT had no predictive value for cholestasis occurrence.Conclusions: Early GGT levels were much higher in neonates, especially preterm...

Aims Weight cycling is defined as cyclical loss and gain of weight and recent studies suggest deleterious effects of weight cycling on cardiometabolic health. We aimed to analyze the risk for diabetes development in association with weight cycling over 4 years of follow-up. Methods A retrospective study performed in 4,818 non-diabetic participants (mean age 43 years, 78.3% men) in a health screening program in whom serial health examinations were performed in 5 consecutive years from 2010 to 2014. Average successive variability of weight (ASVW) was defined by the amount of body weight change in absolute value between the successive years over 5 years summed and divided by four. The subjects were divided into two groups according to body mass index (BMI), normal weight ( Results Over 4 years, 3.2% developed diabetes. When the subjects were divided into 3 groups according to tertile groups of ASVW, those in the highest tertile showed significantly increased risk for diabetes development compared to those with the lowest tertile {odds ratio (OR) 1.860; 95% CI 1.130–3.063}. When similar analyses were performed according to the 4 groups divided by baseline body weight and ASVW over four years, those who were more than overweight at baseline with high ASVW showed significantly increased risk of diabetes development compared to those had normal weight and low ASVW (OR 2.266; 95% 1.123–4.572). When the subjects were divided into six group according to weight change and ASVW, those with increased weight over 4 years and high ASVW showed the highest risk for diabetes development among the groups compared to those with stable weight and low ASVW over four years (OR 3.660; 95% CI 1.402–9.553). Conclusions Those with high ASVW showed significantly increased risk for diabetes development over four years compared with those who had low ASVW. Weight cycling was significantly associated with increased risk for diabetes.

We aimed to identify whether rotavirus, human parechovirus, or enterovirus are causative or associated viral pathogens of seizures accompanied by diffuse cerebral white matter injury in neonates. Thirty neonates who presented with seizures and diffusion-restriction in the widespread bilateral cerebral white matter on diffusion-weighted magnetic resonance imaging (MRI) were included in this study. All patients were tested for rotavirus, human parechovirus, and enterovirus by using reverse transcription PCR. Stool, cerebrospinal fluid, and serum samples were examined in 30, 25, and 20 patients, respectively. Rotavirus was detected in stool samples from all 30 patients (100%). Stool samples from 5 patients (16.7%) were also positive for enterovirus. Rotavirus or human parechovirus were not detected in any cerebrospinal fluid samples from 25 patients, but 1 patient tested positive for enterovirus. No virus was detected in any of 20 patient sera. This study indicated an association between rotavirus and seizures accompanied by diffuse cerebral white matter lesions in neonates.

Background and Aims We undertook this study to compare the prevalence of coronary artery calcification (CAC) across glycated hemoglobin A1c (HbA1c) in nondiabetic males and to evaluate the impact of insulin resistance on CAC in relation to HbA1c levels. Methods A cross-sectional study was performed in 18,504 adult males without diabetes mellitus and cardiovascular disease (CVD). CAC scores were measured by multidetector computed tomography; CAC was defined as a CAC score >0. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Subjects were grouped by HbA1c quartile (≤5.4%, 5.4–5.6%, 5.7%, 5.8–6.4%). Results Thirteen percent of subjects ( n = 2,406) had a CAC score >0. The prevalence of CAC increased with increasing HbA1c quartile (9.4%, 11.1%, 14.1%, 17.3%). Crude odds ratios (ORs) for CAC were 1.2, 1.58 and 2.01 for the HbA1c quartiles 2, 3, and 4 when compared with the first quartile. Mean HOMA-IR levels were different among HbA1C categories and CAC status. HOMA-IR levels were higher in subjects with CAC than in those without, except in the third HbA1c quartile. Stratification by HbA1c showed a significant association between CAC and insulin resistance only in the first (OR 1.67) and fourth (OR 1.33) HbA1c quartile. After adjustment for CV risk factors, insulin resistance remained an independent predictor of CAC only in the first HbA1c quartile. Conclusions Our study demonstrated that not only glucose status represented by HbA1c but also insulin resistance might be associated with CAC in non-diabetic Korean men. The magnitude of association of CAC with insulin resistance was greater in the lowest HbA1c quartile group.

Background The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear. Methods To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation. Results Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels. Conclusion Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus.

Aims To evaluate whether variable fatty liver status over time influence the risk of type 2 diabetes differently. Methods We analyzed the data from 7849 subjects without type 2 diabetes who underwent comprehensive health check-ups annually for 5 years. All subjects had an abdominal ultrasonography annually. The risk of incident diabetes was assessed in individuals with sustained non-alcoholic fatty liver disease (NAFLD), individuals with changed fatty liver status (intermittent NAFLD group), and individuals who did not have NAFLD (never NAFLD group) during the study period. A subgroup analysis was done in subjects of the intermittent NAFLD group. Incident diabetes was compared according to the number of time diagnosed as NAFLD by annual ultrasonography. Results During the mean follow-up of 4 years, subjects in the sustained NAFLD group had a HR of 1.50 (95% CI 1.13–1.98) for the development of diabetes compared with those in the never NAFLD group, whereas the risk was not higher in the intermittent NAFLD group (HR 0.99, 95% CI 0.76–1.31). When compared with the intermittent NAFLD group, multivariable adjusted HR for incident diabetes was 1.50 (95% CI 1.20–1.89) in the sustained NAFLD group. As the number of times diagnosed as NAFLD increased, the proportion of subjects who developed diabetes also increased (p = .002). Conclusions The presence of fatty liver was differentially associated with incident diabetes based on its duration. The persistence of fatty liver status is an important factor for an independent association between NAFLD and incident diabetes.

Context The hemoglobin glycation index (HGI) is known to be correlated with the risk for cardiovascular disease. Objective To analyze the association between incident coronary artery calcification (CAC) and the changes in HGI among participants without diabetes, over 4 years. Design, setting, participants, and outcome measures A retrospective study of 2052 nondiabetic participants in whom the coronary artery calcium score was measured repeatedly over 4 years, as part of a health checkup program in Kangbuk Samsung Hospital in Korea, and who had no CAC at baseline. The HGI was defined as the difference between the measured and predicted hemoglobin A1c (HbA1c) levels. Results A total of 201 participants developed CAC after 4 years, and the mean baseline HGI was significantly higher in those patients. The incidence of CAC gradually increased from the first to the fourth quartile groups of baseline HGI. The odds ratio (OR) for incident CAC was the highest among the four groups divided by the quartiles of the baseline HGI and was significant after adjustment for confounding variables (vs first quartile group: OR, 1.632; 95% confidence interval, 1.024 to 2.601). The incidence of and risk for CAC development were significantly higher than in other groups compared with the low-to-low group after adjustment for confounding factors; however, when baseline HbA1c level was included in the model, only participants with a low-to-high HGI over 4 years showed a significantly increased OR for CAC development compared with the low-to-low group (OR, 1.722; 95% confidence interval, 1.046 to 2.833). Conclusions The participants with a high baseline HGI and consistently high HGI showed a higher risk for incident CAC than those with a low baseline HGI. An increased HGI over 4 years significantly increased the risk for CAC regardless of the baseline HbA1c levels.

Introduction The number of citations that an article has received reflects its impact on a particular research area. Evidence acquisition We determined the one-hundred most-cited articles in thyroid research via the Institute for Scientific Information Web of Knowledge database, using the search term. The following parameters were used to analyze the characteristics of the 100 most-cited articles: publication year, journal (including subject category and impact factor), number of citations and annual citations, authors, department, institution, country, type of study, and topic. Evidence synthesis The number of citations for the 100 most-cited articles ranged from 2521 to 412 (mean, 643.4) and the number of annual citations ranged from 392.9 to 7.1 (mean, 38.0). The majority of articles were published in 2000-2009 (32%), published in endocrinology journals (29%), originated in the USA (70%), were clinical observation study (31%), and dealt with nodular thyroid disease (32%). Department of Internal Medicine, Johns Hopkins University School of Medicine and Department of Internal Medicine, Ohio State University College of Medicine (N.=6 each) were the leading institutions and Mazzaferri EL (N.=7) was the most prolific author. Conclusions Our study presents a detailed list and analysis of the 100 most-cited thyroid research articles, which provides a unique insight into the historical development in this field.

An adequate supply of vitamin D is considered necessary for osteoporosis management and fracture prevention. Intermittent high-dose vitamin D supplementation is an effective and convenient way to achieve and maintain sufficient vitamin D status. However, the long-term effectiveness of supplementation for preventing falls and fractures is unclear, and some deleterious effects of such treatments have been reported. Concerning these issues, the Korean Society for Bone and Mineral Research task force team reviewed previous clinical trials and provided the following perspectives based on current evidence: 1) An adequate supply of vitamin D is necessary for preventing falls and fractures in postmenopausal women and men older than 50 years. An oral intake of 800 to 1,000 IU/day of vitamin D is generally recommended. 2) Care should be taken concerning the routine use of intermittent high-dose vitamin D, as large-scale clinical trials showed increased risk of falls or fractures after high-dose vitamin D administration. Intermittent high-dose vitamin D supplementation is recommendable only in cases of malabsorption or when oral administration is not suitable. 3) Monitoring of the serum level of 25-hydroxy-vitamin D (25[OH]D) is advisable, especially when intermittent high-dose vitamin D is used for supplementation. The task force team suggests that a serum 25(OH)D level of >20 ng/mL is generally appropriate for the prevention of osteoporosis, and that a serum 25(OH)D level of >30 ng/mL is probably helpful both for the management of osteoporosis and the prevention of fractures and falls. However, serum 25(OH)D level >50 ng/mL (this value can vary depending on the measurement method used) is unnecessary and may be undesirable. These perspectives are relevant for the management of osteoporosis, falls, or fractures. Other metabolic bone diseases or non-skeletal disorders are not within the scope of these perspectives.

Background Recent studies suggest an association between Lipoprotein(a) [Lp(a)] and the development of diabetes mellitus. We analyzed the association between baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a population of apparently healthy Korean subjects. Methods A total of 2,536 non-diabetic participants (mean age: 41 years, men: 92%) of a health checkup program were included in the study. Diabetes development was defined by fasting blood glucose ≥126 mg/dL, HbA1c ≥6.5%, and self-reported treatment of diabetes. Homeostasis model assessment (HOMA) indices were used to assess insulin resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was defined by being in the highest quartile of HOMA-IR and in the lowest quartile HOMA-IS. Results After four years, 3.4% of the participants developed diabetes. The odds ratio (OR) of developing diabetes was lowest in the 4th quartile group of baseline Lp(a) (0.323 [95% CI 0.153–0.685])with the 1st quartile group as the reference. The subjects with both IR & impaired IS plus baseline Lp(a)

Rhesus D (RhD) alloimmunization is the most severe cause of hemolytic disease of the fetus and newborn (HDFN). However, owing to medical advances, pediatricians are likely to encounter only a few relatively mild cases. Therefore, although late-onset anemia is a well-recognized complication of HDFN, it may be overlooked in evaluations for post-discharge surveillance. Herein, we report a case of severe late-onset anemia associated with RhD HDFN. A 37-day-old male infant presented with a marked pale appearance. During the fetal period, he had received intrauterine transfusion six times for the treatment of severe anemia induced by RhD HDFN. However, during the neonatal period, he had no significant clinical manifestations, except mild jaundice. The laboratory findings on the day of presentation showed severe hemolytic anemia with reticulocytosis, which was treated with red blood cell transfusion. Our case report emphasizes that regardless of the initial disease severity during the neonatal period, regular follow-up visits and close monitoring for late-onset anemia in the first several weeks after birth are vital in infants with HDFN.

The liver of a newborn is vulnerable to damage during the process of delivery or on external manipulation. Although hepatic subcapsular hematoma occurs relatively commonly in the perinatal period, it is clinically unnoticeable in the majority of the cases. We report two cases of hepatic subcapsular hematoma in neonates who presented with different clinical features. The first newborn was a macrosomic full-term infant. He presented with severe hyperbilirubinemia, requiring intensive phototherapy and exchange transfusion twice within 8 days of life. In contrast, the other baby was a very low-birth-weight preterm infant, resuscitated with endotracheal intubation and chest compression due to asphyxia. He presented with severe pallor, uncontrolled bleeding tendency, and hemorrhagic shock which suddenly lead to catastrophic result. Identifying the high-risk patients and various clinical characteristics is crucial for the early detection and proper management of hepatic subcapsular hematoma in newborns.

Background/Aims: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evalu ated in previous studies. Methods: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components. Results: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of cri teria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to ≥ 3 (p for trend < 0.001). Conclusions: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.

Thyroid dysfunction affects clinical complications in preterm infants and older children. However, thyroid hormone replacement in preterm infants has no proven benefits, possibly owing to the lack of an appropriate reference range for thyroid hormone levels. We aimed to establish a reference range for triiodothyronine (T3) levels at 1-month postnatal age (PNA) in preterm infants.This retrospective study included preterm infants born at a tertiary referral neonatal center at gestational age (GA)35 weeks with no apparent thyroid dysfunction, for 6 consecutive years, with follow-up from PNA 2 weeks to 16 weeks. Using thyroid function tests (TFT), the relationships between T3 levels and thyrotropin (TSH) and free thyroxine (fT4) levels, birth weight, GA, postmenstrual age (PMA), and PNA were examined. The conversion trend for fT4 to T3 was analyzed using the T3/fT4 ratio.Overall, 464 TFTs from 266 infants were analyzed, after excluding 65 infants with thyroid dysfunction. T3 levels increased with fT4 levels, birth weight, GA, PMA, and PNA but not with TSH levels. The T3/fT4 ratio also increased with GA, PNA, and PMA. The average T3 level at 1 month PNA was 72.56 ± 27.83 ng/dL, with significant stratifications by GA.Relatively low T3 and fT4 levels in preterm infants were considered normal, with T3 levels and conversion trends increasing with GA, PMA, and PNA. Further studies are required to confirm the role of the present reference range in thyroid hormone replacement therapy.

Background Chronic kidney disease (CKD) is considered one of the most common risk factors for cardiovascular disease. Coronary artery calcification (CAC) is a potential mechanism that explains the association between renal function and cardiovascular mortality. We aimed to evaluate the association between renal function and CAC in apparently healthy Korean subjects. Methods A total of 23,617 participants in a health-screening program at Kangbuk Samsung Hospital were included in the study. Estimated glomerular filtration rate (eGFR) was assessed using the Cockcroft-Gault equation. Coronary artery calcium score (CACS) was measured via multidetector computed tomography. Subjects were divided into three groups according to the CKD Staging system with eGFR grade: stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stage 3, eGFR 30 to 59 mL/min/1.73 m2. Results The mean age of the participants was 41.4 years and the mean eGFR was 103.6±21.7 mL/min/1.73 m2. Hypertension and diabetes were noted in 43.7% and 5.5% of the participants, respectively. eGFR showed a weakly negative but significant association with CACS in bivariate correlation analysis (r=-0.076, P

Some full-term neonates presenting seizures show diffusion-restricted lesions in the cerebral white matter on brain diffusion-weighted imaging (DWI). The purpose of this study was to describe the clinical characteristics and DWI findings in a group of neonates with seizures, white matter lesions on DWI, and a high incidence of rotavirus infection.Total 30 full-term neonates with seizures were admitted between 2008 and 2010. Of these, 13 (group A) had the following characteristics on brain DWI: (1) diffusion-restricted lesions in the diffuse symmetric cerebral white matter, including the corpus callosum, and (2) no cerebral cortical lesions. The remaining 17 patients (group B) did not exhibit the DWI findings. The clinical characteristics were compared between the 2 groups.The 1-min and 5-min Apgar scores ranged between 7 and 10 in all group A patients, whereas the scores were more diverse in the group B patients. Patients' age at seizure onset was 4.6 ± 0.6 days (range, 4-6 days) in group A and 8.3 ± 7.4 days (range, 1-27 days) in group B. Twelve of 13 patients (92.3%) in group A tested positive for stool rotavirus antigen, while only 2 of 12 (16.7%) in group B tested positive (p 0.001). Six of 10 group A patients showed normal neurodevelopment, but 4 had delayed development between 6 and 30 months.Rotavirus infection should be considered in neonates with seizures accompanied by diffuse cerebral white matter lesions on DWI, particularly around 5 days of life.

Objective Hepatokine fibroblast growth factor (FGF) 21 takes part in the regulation of lipid metabolism in the liver and adipose tissue. We investigated whether exendin-4 regulates the expression of FGF21 in the liver, and whether the effects of exendin-4 on the regulation of FGF21 expression are mediated via silent mating type information regulation 2 homolog (SIRT) 1 or SIRT6. Materials/methods The C57BL/6J mice were fed a low fat diet, high fat diet, or high fat diet with 1 nmol/kg/day exendin-4 intraperitoneal injection for 10 weeks. HepG2 used in vitro study was treated with palmitic aicd (0.4 mM) with or without exendin-4 (100 nM) and FGF21 (50 nM) for 24 hours. The change of FGF21 and its receptors expression by exendin-4 were measured using quantitative real-time RT-PCR and Western blot. The intracellular lipid content in HepG2 cells was evaluated by Oil Red O staining. Inhibition of FGF21, SIRT1 and SIRT6, by 10 nM siRNA was performed to establish the signaling pathway of exendin-4 action in hepatic lipid metabolism. Results Exendin-4 increased the expression of FGF21 and its receptors in high fat diet-induced obese mice. In addition, recombinant FGF21 treatment reduced lipid content in palmitic acid-treated HepG2 cells. We also observed significantly decreased expression of peroxisomal proliferator-activated receptor (PPAR) α and medium-chain acyl-coenzyme A dehydrogenase (MCAD) in hepatocytes transfected with FGF21 siRNA. In cells treated with exendin-4, inhibition of SIRT1, but not SIRT6, by siRNA significantly repressed the expression of FGF21 mRNA, whereas decreased SIRT1 expression by inhibition of FGF21 was not observed. Conclusions These data suggest that exendin-4 could improve fatty liver by increasing SIRT1-mediated FGF21.

Adiponectin and tumor necrosis factor‑α (TNF‑α) exert opposite effects on obesity‑associated inflammation and insulin signaling. The purpose of the present study was to investigate the effects of chronic TNF‑α on adiponectin levels in 3T3‑L1 adipocytes, as well as the potential reversal mechanisms. Differentiated 3T3‑L1 adipocytes were exposed to TNF‑α for three different incubation times and then to various wash‑off periods with or without mitogen‑activated protein kinase (MAPK) inhibitors. TNF‑α significantly reduced adiponectin gene expression in a dose‑ and time‑dependent manner and activated c‑Jun N‑terminal kinases (JNK), extracellular signal‑regulated kinases (ERK) and p38 MAPK. A 16 h restoration period fully reversed the decrease in adiponectin levels following 16 h treatment with TNF‑α; however, 16 h withdrawal of TNF‑α following 32 or 48 h treatment did not completely reverse the TNF‑α‑induced decrease in adiponectin levels. In 3T3‑L1 adipocytes, 32 or 48 h wash‑off periods were required following 32 or 48 h TNF‑α treatments, respectively. The pattern of ERK activation following TNF‑α exposure and removal was similar to the pattern of adiponectin expression. Furthermore, ERK1/2 inhibition accelerated the recovery of adiponectin levels compared with the levels in the untreated control adipocytes. Therefore, the inhibitory effects of TNF‑α on adiponectin levels in differentiated 3T3‑L1 cells were fully reversed following a wash‑out period equivalent to the TNF‑α treatment time, potentially through the ERK 1/2 pathway.

Background Intracranial hemorrhage (ICH) is a rare birth injury in term infants. Newborn infants with cephalohematoma (CH) associated with ICH, however, have frequently been found incidentally at Kyungpook National University Hospital; many of them had no neurological symptoms. The aim of this study was to evaluate the clinical manifestations of ICH in newborn infants with CH. Methods Newborn infants with CH in the neonatal intensive care unit were retrospectively evaluated. During period I (5 years), neuroimaging (brain computed tomography and magnetic resonance imaging) was performed when intracranial abnormalities were suspected. During period II (36 months) neuroimaging was performed when CH > 5 cm in diameter was present. Results During period I, seven out of 19 infants who underwent neuroimaging had ICH (36.8%) including two epidural hemorrhages (EDH). During period II, 18 out of 27 infants who underwent neuroimaging had ICH (66.7%), including two EDH. There was no significant difference in the clinical manifestations between infants with and without ICH. In 10 cases of CH accompanied with a linear skull fracture, nine had ICH, including all cases of ICH that needed intervention. Conclusions The association of ICH appears to be common in newborn infants with CH; particularly in infants with CH accompanied with a skull fracture, the rate of ICH was very high, and all cases of EDH requiring intervention were associated with skull fracture. Therefore, evaluation of accompanying skull fracture should be required in infants with CH, and, in cases of skull fracture, neuroimaging should be considered.

Accumulation of excess hepatic lipids contributes to insulin resistance and liver disease associated with endoplasmic reticulum (ER) stress. Exendin-4 is an agonist of the glucagon-like peptide 1 receptor and plays a role in improving insulin resistance and liver disease by increasing silent mating type information regulation 2 homolog (SIRT) 1. However, the effects and mechanism of action of exendin-4 on responses to palmitic acid (PA)-induced ER stress in hepatocytes have not been clearly defined. We investigated whether exendin-4 attenuates PA-induced ER stress via SIRT1 in HepG2 cells. PA treatment induced increased expression of PRKR-like endoplasmic reticulum kinase, inositol-requiring kinase 1α (IRE1α), activating transcription factor 6 (ATF6), and C/EBP homologous protein (CHOP) mRNA. Exendin-4 decreased the expression of P-IRE1α, ATF6, X-box binding protein-1 and CHOP, and increased the expression of SERCA2b. A significant decrease in the hepatic expression of PUMA, BAX, cytochrome c, and cleaved caspase-3 were observed in hepatocytes treated with exendin-4. The TUNEL assay consistently showed that exendin-4 reversed hepatocyte apoptosis induced by treatment with PA. Inhibition of SIRT1 by nicotinamide and siRNA significantly increased the expression of ER stress marker genes in cells treated with both PA and exendin-4. In conclusion, increased SIRT1 by exendin-4 attenuates PA-induced ER stress and mitochondrial dysfunction in hepatocytes.

In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

Background Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects. Methods A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day). Results Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P

Background: Tumor necrosis factor (TNF)-α is associated with insulin resistance and systemic inflammatory responses. The aim of this study was to investigate the relationship between TNF-α and the development of nonalcoholic fatty liver disease (NAFLD) in a longitudinal study. Methods: Three hundred and sixty-three apparently healthy subjects (mean age, 40.5±6.1 years; male, 57.6%) without NAFLD were enrolled in 2003. Anthropometric and laboratory measurements were performed. The participants were grouped into tertiles according to their serum TNF-α levels from samples taken in 2003. At a 4-year follow-up, we compared the odds ratios (ORs) of the development of NAFLD according to the tertiles of TNF-α levels measured in 2003. Results: At the 4-year follow-up, the cumulative incidence of NAFLD was 29.2% (106/363). The group that developed NAFLD had higher levels of TNF-α than those in the group without NAFLD (3.65±1.79 pg/mL vs. 3.15±1.78 pg/mL; P=0.016). When the 2003 serum TNF-α levels were categorized into tertiles: incidence of NAFLD observed in 2007 was significantly higher with increasing tertiles (22.6%, 35.8%, and 41.5%, respectively; P

Background Recent studies have suggested the importance of non-alcoholic fatty liver disease (NAFLD) and systemic inflammation in the development of atherosclerosis. The aim of this study was to compare the risk for coronary artery calcification (CAC) development according to the status of NAFLD and inflammation over four years of follow-up in subjects without baseline CAC. Methods A total of 1,575 participants in a health screening program were divided into four groups according to baseline NAFLD state and high-sensitivity C-reactive protein (hs-CRP) (median 0.06 mg/L) levels as follows: no NAFLD and hs-CRP