Search

Background: Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS).Methods: We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed.Results: rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles.Conclusion: The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

There is still controversy about the association between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD). The aim of this study was to clarify the association between NAFLD and the decline in BMD in healthcare examinees. Participants who underwent regular health check-ups with BMD and hepatic ultrasonography from 2006 to 2015 with more than one follow-up until 2020 were included. Propensity score matching was performed between the NAFLD group and the control group, and mixed linear regression models were used for the longitudinal analysis. Of 2623 eligible participants (mean age 58.7 ± 7.3 years; males 31.3%), 888 (33.9%) had NAFLD. At baseline, the NAFLD group had a higher total hip BMD than the non-NAFLD group in men (0.988 vs. 1.015 g/cm2, p = 0.007); however, there was no difference in baseline BMD in women (p = 0.253). In longitudinal analysis during a follow-up period of 7.1 years, there was no significant difference in the BMD decline rate between the two groups in the PS-matched cohort (p = 0.816 in men and p = 0.827 in women). However, among men with NAFLD, those with a high and intermediate probability of advanced fibrosis by the FIB-4 showed a significantly increased rate of decline in total hip BMD compared to those with low scores (0.01 vs. − 0.19% change/year, p = 0.011). NAFLD was not associated with the total hip BMD decline rate. However, hepatic fibrosis was significantly associated with an increased rate of decline in total hip BMD in men with NAFLD. This study is a retrospective observational study and is not a drug trial. There was no need for clinical trial registration.

Background Although obesity differs according to ethnicity, it is globally established as a solid risk factor for cardiovascular disease. However, it is not fully understood how obesity parameters affect the progression of coronary artery calcification (CAC) in Korean population. We sought to evaluate the association of obesity-related parameters including visceral adipose tissue (VAT) measurement and CAC progression. Methods This retrospective observational cohort study investigated 1,015 asymptomatic Korean subjects who underwent serial CAC scoring by computed tomography (CT) with at least 1-year interval and adipose tissue measurement using non-contrast CT at baseline for a routine checkup between 2003 and 2015. CAC progression, the main outcome, was defined as a difference of ≥2.5 between the square roots of the baseline and follow-up CAC scores using Agatston units. Results During follow-up (median 39 months), 37.5% of subjects showed CAC progression of a total population (56.4 years, 80.6% male). Body mass index (BMI) ≥25 kg/m2, increasing waist circumferences (WC), and higher VAT/subcutaneous adipose tissue (SAT) area ratio were independently associated with CAC progression. Particularly, predominance of VAT over SAT at ≥30% showed the strongest prediction for CAC progression (adjusted hazard ratio, 2.20; P

Background Cefaclor, a second-generation oral cephalosporin, is widely prescribed to treat infectious diseases. Immediate hypersensitivity (HS) reactions to cefaclor have continuously been reported and are expected to increase with its greater use. This study aimed to investigate the clinical characteristics and risk factors of immediate HS to cefaclor over the most recent 5 years. Methods This retrospective study investigated 521 adverse drug reactions (ADRs) to cefaclor at pharmacovigilance centers at two tertiary hospitals from January 2014 to December 2018. In total, 459 patients with immediate HS to cefaclor were reviewed. Results A total of 459 cases of cefaclor immediate HS were included among 521 cefaclor ADRs, and anaphylaxis was recorded in 61.2%. Female sex (odds ratio 2.917, 95% confidence interval 2.397–3.550, P P P P = 0.010), asthma (8.075, 5.301–12.302, P P Conclusions Cefaclor was found to elicit high proportions of immediate HS and anaphylaxis. Physicians ought to be cautious with prescribing cefaclor to females, individuals with hypertension, liver diseases, or asthma, and patients taking nonsteroidal anti-inflammatory drugs. Trial registration This study was retrospectively registered.

Objective: The association between nonfunctioning adrenal incidentalomas (NFAIs) and cardiometabolic diseases remains controversial. This retrospective cohort study investigated whether NFAIs are related with prevalent and incident cardiometabolic diseases. Methods: This study included 154 patients with biochemically confirmed NFAIs and 1:3 age and sex-matched controls without AIs (n=462) among subjects who underwent abdominal computed tomography at a single healthcare center in 2003-2012. Electronic medical records were reviewed for comorbidities at baseline and during a mean follow-up of 7.5 years. The logistic regression analysis for prevalent cardiometabolic diseases and the survival analysis for incident cardiometabolic diseases were performed. Results: The subjects were 55.7±8.8 years of age and predominantly male (73.1%). The NFAI group had a higher BMI compared to the age and sex-matched control group (25.1±2.8 vs. 24.0±2.8 kg/m2, P

Background : The association between nonalcoholic fatty liver disease (NAFLD) and sarcopenia has been suggested. We investigated the association between sarcopenia and NAFLD independent of visceral adiposity and searched for the clinical characteristics that affect this association. Methods : We performed a retrospective study including of 5,989 subjects (mean age, 53.2 years; men, 57.3%) who underwent bioelectrical impedance analysis (BIA) and abdominal ultrasonography in 2012. The appendicular skeletal muscle mass (ASM) was assessed by BIA method. Sarcopenia was defined as ASM/weight (ASM%)

Context Although blood pressure variability (BPV) is associated with various health outcomes, only 1 study suggested that BPV is correlated with hip fractures. As cardiovascular disease and fractures share similar pathophysiology, there might be a link between BPV and fractures. Objective To investigate the association between BPV and the incident fractures. Design Retrospective cohort study. Setting Population-based, using the Korean National Health Insurance System database. Patients or Other Participants A total of 3 256 070 participants aged ≥50 who participated in ≥3 health examinations within the previous 5 years, including the index year (2009-2010), were included. Outcome data were obtained through the end of 2016. Exposure BPV was calculated using variability independent of the mean. High variability was defined as the highest quartile of variability. Main Outcome Measures Newly diagnosed fractures. Results During the median follow-up of 7.0 years, there were 337 045 cases of any fracture (10.4%). After adjusting for age, sex, income, lifestyle factors, and comorbidities, a higher risk of fracture was observed with higher quartiles of BPV than the lowest quartile group: the adjusted hazard ratios (95% CIs) for incident any fracture were 1.07 (1.06-1.08) in the higher quartile of systolic BPV, 1.06 (1.05-1.07) in that of diastolic BPV, and 1.07 (1.06-1.08) in that of both systolic and diastolic BPV. Consistent results were noted for vertebral fractures and hip fractures, as well as in various subgroup analyses. Conclusions A positive association was noted between higher BPV and fracture incidence. BPV is an independent predictor for developing fracture.

Objectives Diabetes appears to decrease the risk of subarachnoid hemorrhage. However, it is not clear whether diabetes decreases the risk of aneurysm formation. The aim of our study to evaluate the risk of unruptured cerebral aneurysm in patients with diabetes mellitus. Methods We used data from participants who underwent brain magnetic resonance angiography (MRA) and laboratory tests at the Healthcare System Gangnam Center of Seoul National University Hospital between January 2010 and December 2013. From the 17,368 participants who underwent brain MRA, we analyzed 16,337 subjects whose diabetes status could be identified. Results The number of participants with diabetes was 2299 (14.1%). The proportion of participants with cerebral aneurysms was 2.3% in the diabetic group and 2.7% in the non-diabetic group, which was not significantly different (P = 0.225). There were no significant differences in the size, location, and multiplicity of aneurysms between the diabetes and control groups. In multivariate logistic regression, older age showed significant risk effects on cerebral aneurysms, but female sex, hypertension, diabetes, obesity, and smoking did not show significant risk effects. Conclusion In this study, diabetes did not affect the risk of cerebral aneurysm formation. In addition, neither smoking, nor hypertension was a significant risk factor for unruptured cerebral aneurysms. The lack of association between cerebral aneurysm and the traditional risk factors for subarachnoid hemorrhage requires further study. Risk factors for cerebral aneurysm development and those for cerebral aneurysm rupture may be different.

Background: An association between nonalcoholic fatty liver disease (NAFLD) and low vitamin D levels has been suggested. We investigated the relationship between vitamin D and NAFLD assessed by controlled attenuation parameter (CAP). Methods: We conducted a retrospective cohort study of apparently healthy subjects who underwent Fibroscan during health screening tests. NAFLD was diagnosed using CAP values. Results: Among the 1202 subjects (mean age 57.2 years, 60.6% male), 630 (52.4%) subjects had NAFLD with CAP ≥ 248 dB/m. Multivariable analysis was conducted after adjusting for metabolic risk factors including diabetes, hypertension, hypercholesterolemia, body mass index, high-density lipoprotein cholesterol, triglyceride and smoking. Higher vitamin D levels showed a lower risk of NAFLD compared to the lowest quartile of vitamin D in a dose-dependent manner (OR 0.68, 95% CI 0.47–1.00 in Q2 vs. Q1, OR 0.65, 95% CI 0.44–0.94 in Q3 vs. Q1, and OR 0.64, 95% CI 0.44–0.94 in Q4 vs. Q1). The highest quartile of vitamin D showed a decreased risk of a severe grade of steatosis (CAP ≥ 302 dB/m) compared to the lowest quartile (OR 0.52, 95% CI 0.31–0.87 in Q4 vs. Q1). Conclusions: Higher levels of serum vitamin D were associated with a decreased risk of CAP-defined NAFLD, compared to low levels of serum vitamin D. The association between NAFLD and vitamin D suggests that vitamin D may exert a protective role against NAFLD.

Background Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of diabetes but has been rarely investigated in young adults. In this study, we investigated the relationship between NAFLD and incident diabetes risk in young adults using nationwide Korean population data. Methods This population-based cohort study from the Korean National Health Insurance Service included adults aged 20 through 39 years who underwent a health examination from 2009 to 2012. NAFLD was defined as a fatty liver index (FLI) ≥60 in the absence of alcohol consumption of ≥30 g/day. Newly diagnosed diabetes during follow-up was identified using claims data. Cox regression was used to calculate the hazard ratio for incident diabetes after adjusting for classical confounders. Findings Among the 5,254,786 participants, 9.3% had an FLI ≥60. During the median follow-up of 8.6 years, 91,885 cases of incident diabetes occurred. In multivariable analysis, the risk of incident diabetes was significantly higher in the NAFLD group than the control group (adjusted hazard ratio = 4.97, 95% confidence interval, 4.90–5.05). Stratified analyses showed higher associations in those who were ≥30 years, male, obese, smokers, alcohol consumers, and did not regularly exercise (all P Conclusions NAFLD is associated with a five-fold increased risk of incident diabetes in young adults. These results suggest an independent high risk for incident diabetes in young adults and underscore the importance of paying early attention to patients who develop NAFLD before middle age.

Background: An association between sarcopenic obesity and cardiovascular disease has been suggested. We investigated the relationship between sarcopenia and coronary atherosclerosis, taking into account the presence or absence of obesity in a health check-up population.Methods: Data were reviewed for subjects who underwent bioelectrical impedance analysis (BIA) and coronary calcium scoring (CAC) computed tomography between January 2017 and December 2018. Appendicular skeletal muscle mass (ASM) was assessed using BIA. Sarcopenia was defined as reduction of muscle mass and calculated as ASM% (ASM/body weight) more than two standard deviations below the sex-specific mean for healthy young adults. CAC scores were dichotomized as low (Results: Among 1,282 subjects (mean age, 58.1 years; 75.5% male), the prevalence of high CAC was 21%. When the study population was divided into four groups according to their obesity and sarcopenia status, the prevalence of high CAC in the sarcopenic-obesity (SO) group was significantly higher than in the other groups (40.7%, P < 0.001). After adjusting for age, sex, hypertension, diabetes, dyslipidemia, and creatinine, subjects with SO exhibited a significantly higher odds of a high CAC score, compared with the non-sarcopenic, non-obese group (odds ratio, 1.92; 95% confidence interval, 1.16–3.18, P = 0.011).Conclusion: SO was significantly associated with CAC, independent of known risk factors for coronary artery disease. These findings suggest that sarcopenia and obesity may potentiate each other to increase atherosclerotic burden in coronary arteries, which may eventually lead to adverse cardiovascular events.

Background and aims We investigated the association between the patatin-like phospholipase domain-containing-3 (PNPLA3) rs738409 genotype and the risk of diabetes mellitus (DM) using a biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) cohort and a longitudinal observational cohort. Methods Associations between genotypes and the prevalence of DM were evaluated with stratification according to the histological severity of NAFLD in the Boramae cohort (n = 706). A longitudinal cohort consisting of nondiabetic individuals with ≥2 health checkups was then selected to investigate the risk of incident DM according to the genotype (the GENIE cohort; n = 4998). Results Among subjects with NAFLD in the Boramae cohort, the G allele was independently associated with a lower prevalence of DM in both NAFL (odds ratio [OR] per 1 allele, 0.66; 95% confidence interval [CI], 0.46–0.97) and nonalcoholic steatohepatitis (OR per 1 allele, 0.59; 95% CI, 0.38–0.92). This result was replicated in the longitudinal GENIE cohort. The G allele was associated with a lower risk of incident DM during the median follow-up of 60 months in subjects with NAFLD (hazard ratio, 0.65; 95% CI, 0.45–0.93). In contrast, G allele carriers without NAFLD showed higher odds for DM in the context of the Boramae cohort (OR, 2.44; 95% CI, 1.00–5.95). Conclusions These findings clarify conflicting results regarding the association between the PNPLA3 rs738409 genotype and the risk of DM, demonstrating a clear difference between subjects with and without NAFLD; this difference might be explained by the low metabolic risk in genetic NAFLD.

Key Points Question Are female reproductive factors associated with bone health in postmenopausal women? Findings In this population-based cohort study of 1 272 115 postmenopausal Korean women, later menarche, earlier menopause, and shorter reproductive span were each independently associated with increased risk of fracture. Meaning This study’s findings suggest that female reproductive factors are independent risk factors for fracture incidence, with a higher risk associated with shorter lifetime endogenous estrogen exposure., Importance Although estrogen level is positively associated with bone mineral density, there are limited data on the risk of fractures after menopause. Objective To investigate whether female reproductive factors are associated with fractures among postmenopausal women. Design, Setting, and Participants This population-based retrospective cohort study used data from the Korean National Health Insurance Service database on 1 272 115 postmenopausal women without previous fracture who underwent both cardiovascular and breast and/or cervical cancer screening from January 1 to December 31, 2009. Outcome data were obtained through December 31, 2018. Exposures Information was obtained about reproductive factors (age at menarche, age at menopause, parity, breastfeeding, and exogenous hormone use) by self-administered questionnaire. Main Outcomes and Measures Incidence of any fractures and site-specific fractures (vertebral, hip, and others). Results Among the 1 272 115 participants, mean (SD) age was 61.0 (8.1) years. Compared with earlier age at menarche (≤12 years), later age at menarche (≥17 years) was associated with a higher risk of any fracture (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.17-1.31) and vertebral fracture (aHR, 1.42; 95% CI, 1.28-1.58). Compared with earlier age at menopause (, This cohort study uses data from the Korean National Health Insurance System database to investigate whether female reproductive factors are associated with fractures among postmenopausal women in Korea.

Background Aging populations are often accompanied by comorbidity and polypharmacy, leading to increases in adverse drug reactions (ADRs). We sought to evaluate the causes and characteristics of ADRs in older Korean adults (≥65 years) in comparison to younger individuals ( Methods Of 37,523 cases reported at a Korean pharmacovigilance center from 2011 to 2018, we reviewed 18,842 ADRs of certain or probable causality on the basis of WHO-UMC criteria. We estimated the number of ADRs per 1000 patients exposed to the major culprit drugs, and incidence rate ratios were obtained to assess high- and low-risk medications in older adults. Results In total, 4152 (22.0%) ADRs were reported for 3437 older adults (mean age, 74.6 years and 57.3% female). Tramadol (rate ratio, 1.32; 95% confidence interval [CI], 1.21–1.44; P P = 0.002) posed higher risks of ADRs in the older adults, whereas nonsteroidal anti-inflammatory drugs (NSAIDs) (0.35, 0.30–0.40, P P P P = 0.001) were higher in the older adults than in the younger patients. Analgesics primarily elicited cutaneous ADRs in the younger patients and gastrointestinal reactions in the older adults. ICM more commonly led to anaphylaxis in the older adults than the younger patients (3.0% vs. 1.6%, P = 0.019). Conclusion For early detection of ADRs in older adults, better understanding of differences in the causes and characteristics thereof in comparison to the general population is needed.

We aimed to investigate long-term cardiovascular sequelae after coronary artery bypass grafting (CABG) in patients with subclinical hypothyroidism (SCH). All-cause and cardiovascular-related mortality, and cardiovascular events were retrospectively reviewed in 222 euthyroid and 36 SCH patients who underwent CABG. During a mean follow-up period of 8.2 ± 4.1 years, there were 90 incidents of all-cause deaths, 20 cardiovascular-related deaths, 70 major cardiovascular adverse events, 6 myocardial infarctions, 12 unstable anginas, 31 strokes, 23 hospitalizations due to heart failure, 15 atrial fibrillation (AF) events, and 27 coronary revascularizations. The incidence rate of coronary revascularization was significantly higher in patients with SCH (n = 6, 16.6%) than in euthyroid patients (n = 20, 9.0%), with a hazard ratio (HR) of 3.179 (95% confidence interval [CI] 1.174, 8.605; p = 0.023) after adjustment. In subgroup analysis, SCH patients who experienced postoperative AF within 3 months after CABG surgery had a significantly higher risk of coronary revascularization (n = 4, 25.0%) than euthyroid patients without AF (n = 14, 8.9%) after adjustment (HR 11.759, 95% CI 2.747, 50.343, p = 0.001). The frequency of fatal or nonfatal unstable angina was also higher in patients with SCH (n = 2, 12.5%) than in euthyroid patients (n = 4, 2.5%) (HR 16.999, 95% CI 2.242, 128.860, p = 0.006). In conclusion, preoperative SCH is associated with less favorable cardiovascular outcomes, especially coronary revascularization after CABG. Moreover, SCH patients who develop postoperative AF exhibit significantly increased risks of unstable angina and coronary revascularization. Preoperative evaluation of thyroid function may be helpful for predicting long-term outcomes after CABG.

Aims To investigate the changes of post-procedural liver transaminase levels after autologous islet transplantation (ITx), and their associations with glycemic outcomes. Methods Non-diabetic patients who underwent distal pancreatectomy for benign tumors were enrolled. Islets isolated from the healthy part of the resected pancreas were transplanted via the portal vein. Metabolic parameters were evaluated in the subjects for 5 years. Results Eight patients completed the study and four developed postoperative diabetes mellitus (PODM). Disposition index (DI) at postoperative 1 year showed prominent difference between the patients who develop PODM or not: DI was preserved in the PODM-free patients (49.7 ± 4.5 to 70.8 ± 14.4, P = 0.182), while it significantly decreased in the PODM patients (69.3 ± 9.9 to 28.5 ± 3.9, P = 0.019). The preoperative liver transaminase levels were not different between the two groups. However, transient increase in liver transaminase levels during the first week after ITx was observed only in the PODM patients, and their peak values demonstrated significant negative correlation with the changes in DI (r = −0.774 for alanine transaminase, r = −0.759 for aspartate transaminase; P Conclusions Elevation of serum transaminases after ITx could be one of the factors determining insulin secretion and PODM.

Context Thyroid nodules are very common, and 7% to 15% of them are diagnosed as thyroid cancer. However, the inherited genetic risk factors for thyroid nodules and their associations with thyroid cancer remain unknown. Objective To identify the genetic variants associated with susceptibility to thyroid nodules in comparison with thyroid cancer. Design and Setting We performed a three-stage genome-wide association study for thyroid nodules. The discovery stage involved a genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a normal thyroid from a population-based cohort. Replication studies were conducted in an additional 1981 cases and 3100 controls from the participants of a health checkup. We also performed expression quantitative trait loci analysis of public data. Results The most robust association was observed in TRPM3 (rs4745021) in the joint analysis (OR, 1.26; P = 6.12 × 10−8) and meta-analysis (OR, 1.28; P = 2.11 × 10−8). Signals at MBIP/NKX2-1 were replicated but did not reach genome-wide significance in the joint analysis (rs2415317, P = 4.62 × 10−5; rs944289, P = 8.68 × 10−5). The expression quantitative trait loci analysis showed that TRPM3 expression was associated with the rs4745021 genotype in thyroid tissues. Conclusions To the best of our knowledge, we have performed the first genome-wide association study of thyroid nodules and identified a susceptibility locus associated with thyroid nodules, suggesting that thyroid nodules have a genetic predisposition distinct from that of thyroid cancer.

This study was performed to compare the prevalence of autoimmune thyroid disease (AITD) assessed by thyroid peroxidase antibody (anti-TPO Ab) and thyroid ultrasonography (USG) in Korean women with polycystic ovary syndrome (PCOS) (

Osteoporosis is hard to detect before it manifests symptoms and complications. In this study, we evaluated machine learning models for identifying individuals with abnormal bone mineral density (BMD) through an analysis of spine X-ray features extracted by deep learning to alert high-risk osteoporosis populations.We retrospectively used data obtained from health check-ups including spine X-ray and dual-energy X-ray absorptiometry (DXA). Consecutively, we selected people with normal and abnormal bone mineral density. From the regions of interest of X-ray images, deep convolutional networks were used to generate image features. We designed prediction models for abnormal BMD using the image features trained by machine learning classification algorithms. The performances of each model were evaluated.From 334 participants, 170 images of abnormal (T scores- 1.0 standard deviations (SD)) and 164 of normal BMD (T scores= - 1.0 SD) were used for analysis. We found that a combination of feature extraction by VGGnet and classification by random forest based on the maximum balanced classification rate (BCR) yielded the best performance in terms of the area under the curve (AUC) (0.74), accuracy (0.71), sensitivity (0.81), specificity (0.60), BCR (0.70), and F1-score (0.73).In this study, we explored various machine learning algorithms for the prediction of BMD using simple spine X-ray image features extracted by three deep learning algorithms. We identified the combination for the best performance in predicting high-risk populations with abnormal BMD.

Background: An association between low muscle mass and nonalcoholic fatty liver disease (NAFLD) has been suggested. We investigated this relationship using controlled attenuation parameter (CAP). Methods: A retrospective cohort of subjects had liver FibroScan® (Echosens, Paris, France) and bioelectrical impedance analyses during health screening exams. Low muscle mass was defined based on appendicular skeletal muscle mass/body weight ratios of one (class I) or two (class II) standard deviations below the sex-specific mean for healthy young adults. Results: Among 960 subjects (58.1 years, 67.4% male), 344 (45.8%, class I) and 110 (11.5%, class II) had low muscle mass. After adjusting for traditional metabolic risk factors, hepatic steatosis, defined as a CAP ≥ 248 dB/m, was associated with low muscle mass (class I, odds ratio (OR): 1.96, 95% confidence interval (CI): 1.38–2.78, class II, OR: 3.33, 95% CI: 1.77–6.26). A dose-dependent association between the grade of steatosis and low muscle mass was also found (class I, OR: 1.88, for CAP ≥ 248, &lt, 302, OR: 2.19, in CAP ≥ 302, class II, OR: 2.33, for CAP ≥ 248, &lt, OR: 6.17, in CAP ≥ 302). High liver stiffness was also significantly associated with an increased risk of low muscle mass (class I, OR: 1.97, 95% CI: 1.31–2.95, class II, OR: 2.96, 95% CI: 1.51–5.78). Conclusion: Hepatic steatosis is independently associated with low muscle mass in a dose-dependent manner. The association between hepatic steatosis and low muscle mass suggests that particular attention should be given to subjects with NAFLD for an adequate assessment of muscle mass.

Background Selenium and iodine are trace elements well known to have important roles in the synthesis and metabolism of thyroid hormones. However, the effects of other trace elements on thyroid hormones are still inconclusive. We investigated the association between several trace elements and thyroid hormones. Methods The data of 448 subjects who were measured for both, trace elements and TSH/free T4, at the Heath Checkup Center were retrospectively reviewed. The presence of thyroiditis (from thyroid echogenicity) and thyroid nodules were reviewed in the subjects who underwent thyroid ultrasonography. Results Blood concentrations of manganese, copper, selenium, and molybdenum were associated with TSH or free T4. After adjusting for age, sex, BMI, smoking, and alcohol consumption, blood copper levels were positively associated with free T4 in both sexes and selenium levels were positively associated with free T4 in women. There was no association between trace elements and thyroiditis. Blood copper concentration had a weak non-linear association with the presence of thyroid nodules. Conclusions This study demonstrated that blood concentrations of copper and selenium were significantly associated with free T4 in healthy Korean subjects with sufficient iodine intake suggesting their role in maintaining normal thyroid function.

Background: Sarcopenia is an aging process characterized by a decline in muscle mass and physical function. Lung function is related to the respiratory muscle mass in patients with chronic lung disease. However, few studies have evaluated the relationship between sarcopenia and lung function in healthy general population. Objectives: We aim to evaluate the association between muscle mass and lung function decline in health check-up population. Methods: The study included the population who checked pulmonary function test (PFT) and bioelectrical impedance analysis (BSA) in 2012 and performed a follow-up PFT in 2016 in Healthcare System Gangnam Center, Seoul. The outcome was the rate of lung function decline during the 4-year follow-up period. Sarcopenia was defined as a value of Appendicular skeletal muscle (ASM)/Height 2 that was ≤ 7.09 Kg/m2 in men , or ≤ 5.27Kg/m2 in women. ASM was calculated as the sum of the muscle masses of the arm and legs by BSA. Results: A total of 2,308 subjects were included in this analysis. The prevalence of sarcopenia was 7.9% (n=161). Baseline lung function including the forced expiratory volume in 1s(FEV1) was significantly lower in sarcopenic subjects than in control (mean FEV1: 2.88 ± 0.67L vs. 3.12 ± 0.69L, P Conclusions: Sarcopenia with obesity is significantly associated with lung function decline.

Type 2 diabetes (T2D) is a common complex disorder with strong genetic predisposition. Although different ethnic groups share most of the common variants of T2D, there might be nonsynonymous variants that are specific to an ethnic group. In this study, we used whole exome sequencing (N=917) and exome genotyping array (N=3,026) to identify nonsynonymous variants in Korean T2D cases and controls (stage 1) and validated the findings in an independent set of 15,095 T2D cases and controls (stage 2). Whole exome capture was prepared using Agilent SureSelect version 4+UTR and sequencing was performed by Illumina HiSeq 2000. Nonsynonymous variants were incorporated into customized Axiom Biobank Plus Genotyping array. Genotype imputation was performed with 1,000 Genomes Project phase 3 reference. In silico data look-up was done for stage 2 analyses. EPACTS software was used for association testing and METAL was used for meta-analysis of stage 1 and 2 results. We identified 728,838 variants using whole exome sequencing, which include 258,463 novel variants. A nonsynonymous variant in GLP-1R (rs3765467, R131Q) was associated with decreased risk of T2D in genome-wide significance (OR = 0.85, P = 3.01x10-8). This variant was associated with lower fasting glucose concentration (P = 0.00020) and lower HbA1c level (P = 0.0085) in nondiabetic controls. The minor allele frequency of this variant was 21.1% in Koreans but it was monomorphic in Europeans. We also validated the previous association between PAX4 nonsynonymous variant (rs2233580, R192H) and increased risk of T2D (OR = 1.52, P = 6.41x10-15). This variant was associated with lower age at diagnosis and decreased C-peptide level in T2D cases (P < 0.05). Gene-wise analysis revealed that SLC30A8 was most significantly associated with decreased risk of T2D (P = 0.00010) by Madsen and Browning method. In summary, we have identified East Asian specific nonsynonymous variants in GLP-1R and PAX4 to be associated with T2D in genome-wide significance. Disclosure S. Kwak: None. J. Chae: None. J. Yoon: None. S. Choi: None. S. Lim: None. M. Moon: None. Y. Cho: None. H. Jang: None. Y. Cho: None. H. Kang: None. J. Kim: None. K. Park: None.

The purpose of this study was to stratify the malignancy risk of US features, with an emphasis on nodule echogenicity.A total of 1,058 nodules of 824 consecutive patients (236 malignant and 822 benign) were included in this study. Malignancy risk of each nodule was analyzed according to US features, with an emphasis on nodule echogenecity, and was stratified into 4-tier categories.In multivariate analysis, isoechogenicity, indistinct margin, non-solid internal content, and parallel orientation were predictive of benign nodules (P 0.002), while hypoechogenicity, marked hypoechogenicity, spiculated/microlobulated margin, solid content, nonparallel orientation (taller than wide), microcalcification, and macrocalcification were predictive of malignancy (P ≤ 0.037). Although the presence of US features associated with malignancy was significantly predictive of malignancy in hypoechoic and markedly hypoechoic nodules (P ≤ 0.004), it was not associated with malignancy in isoechoic or hyperechoic nodules. Thyroid nodules could be stratified into four categories according to the malignancy risk: benign (risk 0%), probably benign (risk ≤ 5%), indeterminate (risk5 and50%), and suspicion of malignancy (risk50%).The US-based four-tier categorization system will be useful for predicting the risk of malignancy and decisions regarding FNA for thyroid nodules.• No US feature was predictive of malignancy in isoechoic nodules. • Isoechoic nodules without calcification can be included in the probably benign category. • We suggest a four-tier categorization stratified primarily by nodule echogenecity. • The four-tier categorization of thyroid nodules will be useful for FNA decisions.

Purpose Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults. Methods A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated. Results PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis. Conclusions In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

The present study investigated the bone mineral density (BMD) and the prevalence of osteoporosis in an ossification of the ligamentum flavum (OLF) patient group and a matched control group. We also investigated the correlation of BMD with the number of spine levels exhibiting OLF. From January 1999 to August 2012, 120 patients with spinal OLF underwent dual-energy X-ray absorptiometry at our institute, and 102 of those were included in our study. Control group members were age, sex, and body mass index (BMI) matched to OLF group members on a 1:1 basis. Age, sex, and BMI were similar in the OLF and control groups. BMDs of the OLF and control groups were significantly different in the lumbar spine (mean T-scores: -0.2 ± 1.5 and -0.7 ± 1.5, respectively; p = 0.03). The prevalences of osteopenia and osteoporosis tended to be lower in the OLF group (28.3% and 4.0%, respectively) than those in the control group (31.3% and 9.1%, respectively); however, the differences were not statistically significant (p = 0.41). A significant positive correlation was detected between the lumbar spine BMD and the number of spine levels exhibiting OLF (p = 0.03).

Data from 540 subjects (included in the obesity group whose BMI was over 25) was selected from 2,445 sub-jects in the 6 th Korean Body Size Survey. A total of 25 direct measurements were selected for the relevant literature lowerbody size measurement analysis, that included 9 components related to BMI, height and circumferences, 3 componentsrelated to width and thickness, 5 components related to length, 3 components related to height, and 2 other components.Descriptive statistics, factor analysis, cluster analysis and variance analysis were executed using PASW 18.0 to analyzethe data. In accordance with the factor analysis results to classify the lower body shape of overweight women in their20s to 60s whose BMI was over 25, 4 factors were identified (lower body volume, leg volume, lower body length and leglength). A total of 4 lower body shapes of overweight women were found through cluster analysis using 4 factor scoresfrom the factor analysis. Body Shape 1 had the largest lower body and leg volume. It was the heaviest group. Leg lengthwas at a normal level. Body Shape 1 was 22.2% (122 subjects). Body Shape 2 had the longest legs and the smallest bodyshape; however, Body Shape 2 was the leg obesity group with the largest leg volume. It was 39.8% (215 subjects). BodyShape 3 had a smaller leg volume in proportion to the lower body thickness and a long lower body length. It comprised27.8% (150 subjects). Body Shape 4 comprised 9.8% (53 subjects) with the shortest leg. Its lower body obesity was ata normal level. Key words:plus-size(플러스 사이즈), lower body shape(하반신 체형), obese women(비만 여성)

The percentage of overweight people has increased in older people due to the change of body shape (including pregnancy and giving birth for women). Obesity is accompanied by body shape changes; subsequently, there are more pattern design considerations compared to standard body shapes. This paper classifies the upper body shape of overweight women in Korea, analyzes features by body shape and proposes basic pattern design data that reflects the features of plus-size women body shapes. The data on 540 subjects in the overweight group (from 20 to 69 years old)whose BMI was over 25 was selected. The following features by shape were identified in accordance with the upper body shape classification of overweight women. Body Shape1 had lower body obesity with long stature and arms in proportion to the trunk length and represented 22.2% of the subjects. Body Shape2 had most parts near average sizes for overweight body shapes with short height and arms that represented 37.6% of the subjects (the highest ratio). Body Shape3 was the smallest body shape in the four groups with the most distinct body figure and represented 30.7% of the subjects. Body Shape4 (9.4% of the subjects)was the upper body obesity type (the fattest group)and with of the waist bigger abdominal obesity type.

In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.

We thank Dr. Moon for his comments in response to our study, "Hyperglycemia is associated with impaired muscle quality in older men with diabetes: The Korean Longitudinal Study on Health and Aging" [1]. The definition of muscle quality is still incompletely established, with various definitions such as: muscle strength per unit muscle mass/cross sectional area (CSA) [2,3], the degree of intramuscular or intermuscular adipose tissue [4,5], muscle fiber type change [6], or histological changes (including myofibrosis and myosteatosis) [7]. Even though it has not reached a consensus yet, muscle strength per muscle mass/area has been widely used as a definition of functional muscle quality in previous studies [2,3,8,9]. As Dr. Moon mentioned, since intramuscular or intermuscular adipose tissue is associated with decreased muscle strength as well as insulin resistance [10,11,12], it is possible that the relationship between severe hyperglycemia and muscle quality impairment is not a cause and effect. Therefore, we performed further analyses in order to evaluate the relationships between muscular fat, insulin resistance, blood glucose level and muscle quality using data from 217 subjects who took a mid-thigh computed tomography scan. The mid-thigh fat (perimuscular subcutaneous fat+intermuscular fat) CSA, not intermuscular fat area or intramuscular fat, was the only measurement available. The mid-thigh muscle-to-fat CSA ratio showed a significant negative correlation with HOMA-IR (r=–0.169, P=0.013), but did not have a significant relationship with fasting blood glucose or glycosylated hemoglobin (HbA1c; r=0.066, P=0.332; r=–0.025, P=0.713, respectively). Moreover, there was no significant association between the mid-thigh muscle-fat ratio and muscle quality (r=0.004, P=0.954). With these results, it is less likely that intermuscular fat confounded the relationship between hyperglycemia and poor muscle quality in our study. As pointed out by Dr. Moon, diabetic complications may contribute to the deterioration of muscle quality. Unfortunately, diabetic complications like peripheral artery disease and diabetic neuropathy were not evaluated in our study participants, and therefore the effects of these conditions could not be excluded. However, we investigated the history of angina pectoris and myocardial infarction, which could reflect the macrovascular complication status. Among the subjects with a history of myocardial infarction or angina pectoris, one (4.8%) was in HbA1c

Summary Objective We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug-naive type 2 diabetic patients. Design, Patients, and Measurements In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0–10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and β-cell function (HOMA-B), insulinogenic index (IGI, defined as 30–0 min insulin/30–0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test. Results After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P

Aims/Introduction: The efficacy, dose-response relationship and safety of ginsam, a vinegar extract from Panax ginseng ,w ere evaluated in an 8-week, double-blind, randomized, placebo-controlled study in drug-naive patients with type 2 diabetes. Materials and Methods: A total of 72 diabetic patients were randomized to receive 1500, 2000 or 3000 mg of ginsam, or placebo daily for 8 weeks (n =1 8 in each group). The primary end-point was the changes from the baseline HbA 1c level. The secondary end-points were the changes of fasting and postprandial 2-h glucose concentration, and the proportion of patients achieving a reduction in HbA1c >0.5%. Results: In the intention-to-treat analysis, ginsam treatment reduced HbA1c level significantly: )0.56 ± 0.25% in the 1500 mg group, )0.31 ± 0.12% in the 2000 mg group, and )0.29 ± 0.11% in the 3000 mg group (all P 0.5% differed significantly between the placebo group (11.1%) and the 1500 mg (27.8%) and 2000 mg (27.8%) groups. No severe adverse events were observed in any group. Conclusions: An 8-week treatment with ginsam, a vinegar extract from P. ginseng, moderately improved HbA1c level and was well tolerated in type 2 diabetic patients with inadequate glycemic control. This trial was registered with ClinicalTrial.Gov (no. NCT01008163). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00185.x, 2012)

Pericardial fat surrounding the heart and coronary arteries might aggravate vessel wall inflammation and stimulate the progression of coronary atherosclerosis. However, there has been little comprehensive evaluation of the effects of pericardial fat on coronary artery disease (CAD). We investigated the relationship between pericardial fat volume and the severity of coronary artery stenosis assessed by computed tomography and angiography among patients with suspected CAD. Participants from the cohort of the Korean Atherosclerosis Study 2 (n = 402, mean age of 54 years, 57.0% men) underwent 64-slice multidetector-row computed tomography (MDCT) to assess pericardial fat amount, coronary artery calcium score (CACS), severity of coronary artery stenosis, and plaque characteristics. Patients with atherosclerotic lesion had significantly larger volume of pericardial fat than patients without atherosclerosis (308 ± 96 cm(3) vs. 251 ± 93 cm(3); P0.01). In a multivariate regression analysis adjusting for age, gender and BMI, subjects with more pericardial fat had a higher risk for significant (50%) stenosed coronary vessels (odds ratio (OR) = 1.012; 95% confidence interval (CI) 1.001-1.030; P = 0.017). This association remained after adjusting for hypertension, diabetes, smoking status, and lipid profiles (OR = 1.007; 95% CI 1.001-1.014; P = 0.042). In conclusion, an increased pericardial fat volume was an independent risk factor for stenotic CAD and could be helpful in assessing subclinical CADs.

OBJECTIVE The number of people with metabolic syndrome is increasing worldwide, and changes in socioenvironmental factors contribute to this increase. Therefore, investigation of changes in metabolic syndrome and its components in South Korea, where rapid socioenvironmental changes have occurred in recent years, would be foundational in setting up an effective strategy for reducing this increasing trend. RESEARCH DESIGN AND METHODS We compared the prevalence and pattern of metabolic syndrome among participants in the Korean National Health and Nutrition Examination Surveys for 1998, 2001, 2005, and 2007. In each survey, stratified, multistage, probability–sampling designs and weighting adjustments were conducted to represent the entire Korean population. The revised National Cholesterol Education Program criteria were used as the definition of metabolic syndrome. All biochemical parameters were measured in a central laboratory. RESULTS A total of 6,907 (mean ± SE age 45.0 ± 0.2 years), 4,536 (45.5 ± 0.2), 5,373 (47.1 ± 0.2), and 2,890 (49.9 ± 0.3) Koreans over 20 years of age have participated in the studies in 1998, 2001, 2005, and 2007, respectively. The age-adjusted prevalence of metabolic syndrome increased significantly from 24.9% in 1998, 29.2% in 2001, and 30.4% in 2005 to 31.3% in 2007. Among the five components, the level of low HDL cholesterol increased the most, by 13.8% over the 10 years. Abdominal obesity and hypertriglyceridemia followed, with 8.7 and 4.9% increases, respectively. CONCLUSIONS Because dyslipidemia and abdominal obesity were major factors in increasing the prevalence of metabolic syndrome in Koreans for the past 10 years, lifestyle interventions should be conducted at the national level to reduce the burden and consequences of metabolic syndrome.

Efficient production of insulin in response to changes in glucose levels has been a major issue for insulin gene therapy to treat diabetes. To express target genes in response to glucose specifically in hepatocytes, we generated a synthetic promoter library containing hepatocyte nuclear factor-1, CAAT/enhancer-binding protein (C/EBP) response element, and glucose-response element. Combinations of these three cis-elements in 3-, 6-, or 9-element configurations were screened for transcriptional activity and then glucose responsiveness in vitro. The most effective promoter (SP23137) was selected for further study. Intravenous administration of a recombinant adenovirus expressing furin-cleavable rat insulin under control of the SP23137 promoter into streptozotocin (STZ)-induced diabetic mice resulted in normoglycemia, which was maintained for >30 days. Glucose tolerance tests showed that treated mice produced insulin in response to glucose and cleared exogenous glucose from the blood in a manner similar to nondiabetic control mice, although the clearance was somewhat delayed. Insulin expression was seen specifically in the liver and not in other organs. These observations indicate the potential of this synthetic, artificial promoter to regulate glucose-responsive insulin production and remit hyperglycemia, thus providing a new method of liver-directed insulin gene therapy for type 1 diabetes.

The age-related increase in body fat and decrease in muscle mass are associated with increased morbidity in elderly populations. Pulmonary function also decreases with age, but no study has investigated whether regional body composition is associated with pulmonary function in an older population. The Korean Longitudinal Study on Health and Aging is a community-based cohort study of people aged > 65 years selected by random stratified sampling. Anthropometrics, biochemical factors, and lung function by spirometry were evaluated in 439 men (mean age of 75.9 ± 8.6 years) and 561 women (mean age of 76.0 ± 8.8 years). Dual-energy X-ray absorptiometry (DXA) was performed to assess the whole and regional body composition. Computed tomography (CT) was also used to measure fat or muscle distribution at the abdominal and mid-thigh levels. Although pulmonary function and muscle mass were inversely related to age, fat mass was not. After adjusting for age, height, BMI, smoking and exercise status, and high sensitivity C-reactive protein (hsCRP), fat mass in trunk or central area was inversely associated with lung function in both sexes (P < 0.01). Men with more muscle in trunk and mid-thigh level had better lung function (P < 0.01). The results of this community-based study show that regional body composition is significantly associated with lung function. Augmentation of muscle in the trunk and low extremity in men, and reduction of fat in the trunk and upper body in men and women may be helpful in maintaining lung function in the elderly population.

OBJECTIVE To improve quality and efficiency of care for elderly patients with type 2 diabetes, we introduced elderly-friendly strategies to the clinical decision support system (CDSS)-based ubiquitous healthcare (u-healthcare) service, which is an individualized health management system using advanced medical information technology. RESEARCH DESIGN AND METHODS We conducted a 6-month randomized, controlled clinical trial involving 144 patients aged >60 years. Participants were randomly assigned to receive routine care (control, n = 48), to the self-monitored blood glucose (SMBG, n = 47) group, or to the u-healthcare group (n = 49). The primary end point was the proportion of patients achieving A1C RESULTS After 6 months of follow-up, the mean A1C level was significantly decreased from 7.8 ± 1.3% to 7.4 ± 1.0% (P < 0.001) in the u-healthcare group and from 7.9 ± 1.0% to 7.7 ± 1.0% (P = 0.020) in the SMBG group, compared with 7.9 ± 0.8% to 7.8 ± 1.0% (P = 0.274) in the control group. The proportion of patients with A1C CONCLUSIONS The CDSS-based u-healthcare service achieved better glycemic control with less hypoglycemia than SMBG and routine care and may provide effective and safe diabetes management in the elderly diabetic patients.

Background: The aim of this study was to investigate sarcopenia and its association with cardiometabolic risk factors in a community-based elderly cohort in Korea. Methods: We recruited 287 men and 278 women aged 65 years or older and without physical disability. Appendicular skeletal muscle mass (ASM) was measured with dual energy X-ray absorptiometry. We used two definitions for sarcopenia-ASM divided by height (kg/m) or by weight (%)

Fluconazole is used as an orally administrated antifungal drug for the treatment of tinea corporis, candidiasis including skin mycotic pneumonia infections. The dosage of fluconazole varies with indication ranging from 50 mg/day to 400 mg/day. The fluconazole capsule 50 mg (3 capsules daily) is already available in Korean market. To improve the patient compliance, a fluconazole tablet 150 mg (once a day administration) was developed recently. The purpose of this study was to evaluate the bioequivalence of three doses of fluconazole capsule 50 mg (Diflucan 50 mg, Pfizer Korea Inc., as a reference drug) and a single dose of fluconazole tablet 150 mg (Plunazol 150 mg, Daewoong Pharm. Co., Korea) according to the guidelines of the Korea Food and Drug Administration (KFDA). The bioequivalence for three capsules of Diflucan 50 mg and a single tablet of Plunazol 150 mg was investigated in twenty-four healthy male volunteers under a randomized 22 crossover trial design. The average age of twenty-four volunteers was 24.783.27 year-old, average height was 175.565.45 cm and average weight was 67.246.86 kg. After three capsules of Diflucan 50 mg or a single tablet of Plunazol 150 mg were orally administered, blood was taken at predetermined time intervals and the plasma concentrations of fluconazole in plasma were determined using LC-MS-MS. The 90% confidence intervals for the main parameters of statistical results after logarithmic transformation were AUCt 0.9272-1.0084 and Cmax 0.8423-0.9544 respectively, which are in the range of log 0.8 to log 1.25 and the statistical results of additional parameters (AUClast, t1/2 and MRT) were also in the 90% confidence interval that is in the range of log 0.8 to log 1.25. Therefore, the results of this study confirm the bioequivalence of three capsules of Diflucan 50 mg to one tablet of Plunazol 150 mg.

Background Some studies have proposed that subclinical hypothyroidism (SCH) has adverse effects on the cardiovascular system, but little is known about the effect on patients undergoing cardiovascular operations. We examined the influence of preoperative SCH on postoperative outcome in patients undergoing coronary artery bypass grafting (CABG). Methods Among patients who underwent CABG between July 2005 and June 2007 at Seoul National University Bundang Hospital, 224 with normal thyroid function and 36 with SCH were enrolled. Preoperative risks and postoperative outcomes were evaluated prospectively without thyroid hormone replacement. Results There were no significant differences in primary outcomes (major adverse cardiovascular events) and secondary outcomes such as wound problems, mediastinitis, leg infection, respiratory complications, delirium, or reoperation during the same hospitalization. However, patients with SCH had a higher incidence of postoperative atrial fibrillation than those with normal thyroid function after adjustment for age, gender, body mass index, and other independent variables such as emergency operation, the use of cardiopulmonary bypass, combined valvular operation, preoperative creatinine levels, left ventricular systolic dysfunction, and nonuse of β-blockers (45.5% vs 29%; odds ratio, 2.552; 95% confidence interval, 1.117 to 5.830; p = 0.026). Conclusions SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.

Extracts of ginseng species show antihyperglycemic activity. We evaluated the antihyperglycemic and antiobesity effects of ginsam, a component of Panax ginseng produced by vinegar extraction, which is enriched in the ginsenoside Rg3. Otsuka Long-Evans Tokushima Fatty rats, an obese insulin-resistant rat model, were assigned into 1 of 3 groups (n = 8 each): controls (isotonic sodium chloride solution, 5 mL/d), rats given 300 mg/(kg d) ginsam, and rats given 500 mg/(kg d) ginsam. An intraperitoneal 2-hour glucose tolerance test was performed at the end of the 6-week treatment. After 8 weeks, body and liver weights, visceral fat measured by computed tomography, and fasting glucose and insulin concentrations and lipid profiles were recorded. Insulin-resistant rats treated with ginsam had lower fasting and postprandial glucose concentrations compared with vehicle-treated rats. Importantly, overall glucose excursion during the intraperitoneal 2-hour glucose tolerance test decreased by 21.5% (P < .01) in the treated rats, indicating improved glucose tolerance. Plasma insulin concentration was significantly lower in ginsam-treated rats. These changes may be related to increased glucose transporter 4 expression in skeletal muscle. Interestingly, when the data from both ginsam-treated groups were combined, body weight was 60% lower in the ginsam-treated rats than in the controls (P < .01). Liver weight and serum alanine aminotransferase concentrations were also lower in the ginsam-treated rats. These effects were associated with increased peroxisome proliferator-activated receptor gamma expression and adenosine monophosphate-activated protein kinase phosphorylation in liver and muscle. Our data suggest that ginsam has distinct beneficial effects on glucose metabolism and body weight control in an obese animal model of insulin resistance by changing the expression of genes involved in glucose and fatty acid metabolism.

Type 2 diabetes mellitus is a common age-dependent disease. We discovered that male offspring of non-diabetic C57BL/6 and DBA/2 mice, called JYD mice, develop type 2 diabetes when they grow old. JYD mice show characteristics of insulin resistance, hyperglycaemia and hyperinsulinaemia in old age without obesity. We postulated that the mechanism of age-dependent type 2 diabetes in this model relates to caveolin-1 status in skeletal muscle, which appears to regulate insulin sensitivity in the mice.We compared insulin sensitivity in aged C57BL/6 and JYD mice using glucose and insulin tolerance tests and (18)F-fluorodeoxyglucose positron emission tomography. We also determined insulin signalling molecules and caveolin proteins using western blotting, and altered caveolin-1 levels in skeletal muscle of C57BL/6 and JYD mice using viral vector systems, to examine the effect of this on insulin sensitivity.In 30-week-old C57BL/6 and JYD mice, the basal levels of IRS-1, Akt and peroxisome proliferator-activated receptor-gamma decreased, as did insulin-stimulated phosphorylation of Akt and insulin receptor beta. However, caveolin-1 was only increased about twofold in 30-week-old JYD mice as compared with 3-week-old mice, whereas an eightfold increase was seen in C57BL/6 mice. Downregulation of caveolin-1 production in C57BL/6 mice caused severe impairment of glucose and insulin tolerance. Upregulation of caveolin-1 in aged diabetic JYD mice significantly improved insulin sensitivity with a concomitant increase of glucose uptake in the skeletal muscle.The level of skeletal muscle caveolin-1 is correlated with the progression of age-dependent type 2 diabetes in JYD mice.

BACKGROUND:Various diabetes risk scores composed of non-laboratory parameters have been developed, but only a few studies performed cross-validation of these scores and a comparison with laboratory parameters. We evaluated the performance of diabetes risk scores composed of non-laboratory parameters, including a recently published Korean risk score (KRS), and compared them with laboratory parameters. METHODS:The data of 26,675 individuals who visited the Seoul National University Hospital Healthcare System Gangnam Center for a health screening program were reviewed for cross-sectional validation. The data of 3,029 individuals with a mean of 6.2 years of follow-up were reviewed for longitudinal validation. The KRS and 16 other risk scores were evaluated and compared with a laboratory prediction model developed by logistic regression analysis. RESULTS:For the screening of undiagnosed diabetes, the KRS exhibited a sensitivity of 81%, a specificity of 58%, and an area under the receiver operating characteristic curve (AROC) of 0.754. Other scores showed AROCs that ranged from 0.697 to 0.782. For the prediction of future diabetes, the KRS exhibited a sensitivity of 74%, a specificity of 54%, and an AROC of 0.696. Other scores had AROCs ranging from 0.630 to 0.721. The laboratory prediction model composed of fasting plasma glucose and hemoglobin A1c levels showed a significantly higher AROC (0.838, P < 0.001) than the KRS. The addition of the KRS to the laboratory prediction model increased the AROC (0.849, P = 0.016) without a significant improvement in the risk classification (net reclassification index: 4.6%, P = 0.264). CONCLUSIONS:The non-laboratory risk scores, including KRS, are useful to estimate the risk of undiagnosed diabetes but are inferior to the laboratory parameters for predicting future diabetes.

The objective of this study was to demonstrate that islet neogenesis-associated protein (INGAP) peptide, a pentadecapeptide containing the biologically active portion of native INGAP, increases functional beta-cell mass in normal animals and can be used therapeutically to reverse hyperglycemia in streptozotocin-induced diabetes.INGAP, a 175 amino acid pancreatic acinar cell protein, has been suggested to be implicated in beta-cell mass expansion.In the first part of this study, normoglycemic hamsters were administered either 500 microg INGAP peptide (n = 30) or saline (n = 20) intraperitoneally daily and sacrificed after 10 or 30 days of treatment. Blood glucose and insulin levels were measured, and a histologic and morphometric analysis of the pancreas was performed to determine the effect of INGAP peptide on the endocrine pancreas. In the second part of the study, 6- to 8-week-old C57BL/6J mice (n = 8) were administered multiple low doses of the beta-cell toxin streptozotocin (STZ) inducing insulitis and hyperglycemia. The mice were then injected with INGAP peptide (n = 4) or saline (n = 4) for 39 days and sacrificed at 48 days. Two additional groups of diabetic mice were administered either a peptide composed of a scrambled sequence of amino acids from INGAP peptide (n = 5) or exendin-4 (n = 5), an incretin that has been associated with amelioration of hyperglycemia.Islet cell neogenesis was stimulated in INGAP-treated hamsters by 10 days. At 30 days, the foci of new endocrine cells had the appearance of mature islets. There was a 75% increase in islet number, with normal circulating levels of blood glucose and insulin. Administration of INGAP peptide to diabetic mice reversed the diabetic state in all animals, and this was associated with increased expression of PDX-1 in duct cells and islet cell neogenesis with a reduction of insulitis in the new islets. Diabetic mice treated with exendin-4 or a scrambled INGAP peptide did not revert from hyperglycemia.Because there is a deficiency of beta-cell mass in both type-1 and type-2 diabetes, INGAP peptide stimulation of fully functional neoislet differentiation may provide a novel approach for diabetes therapy.

Type 1 diabetes results from the destruction of pancreatic beta cells. Genetic factors are believed to be a major component for the development of type 1diabetes, but the concordance rate for the development of diabetes in identical twins is only about 40%, suggesting that non-genetic factors play an important role in the expression of the disease. Viruses are one environmental factor that is implicated in the pathogenesis of type 1 diabetes. To date, 14 different viruses have been reported to be associated with the development of type 1 diabetes in humans and animal models. Viruses may be involved in the pathogenesis of type 1 diabetes in at least two distinct ways: by inducing beta cellspecific autoimmunity, with or without infection of the beta cells, (e.g. Kilham rat virus) and by cytolytic infection and destruction of the beta cells (e.g. encephalomyocarditis virus in mice). With respect to virus-mediated autoimmunity, retrovirus, reovirus, Kilham rat virus, bovine viral diarrhoea-mucosal disease virus, mumps virus, rubella virus, cytomegalovirus and Epstein-Barr virus are discussed. With respect to the destruction of beta cells by cytolytic infection, encephalomyocarditis virus, mengovirus and Coxsackie B viruses are discussed. In addition, a review of transgenic animal models for virus-induced autoimmune diabetes is included, particularly with regard to lymphocytic choriomeningitis virus, influenza viral proteins and the EpsteinBarr viral receptor. Finally, the prevention of autoimmune diabetes by infection of viruses such as lymphocytic choriomeningitis virus is discussed.

Type 1 diabetes results from the progressive destruction of insulin-producing pancreatic beta cells. Although the etiology of type 1 diabetes is believed to have a major genetic component, studies on the risk of developing type 1 diabetes suggest that environmental factors, such as viruses, may be important etiological determinants. Among the viruses, the most clear and unequivocal evidence that a virus induces type 1 diabetes in animals comes from studies on the D variant of encephalomyocarditis (EMC-D) virus in mice and Kilham rat virus (KRV) in rats. A high titer of EMC-D viral infection results in the development of diabetes within 3 days, primarily due to the rapid destruction of beta cells by viral replication within the cells. A low titer of EMC-D viral infection results in the recruitment of macrophages to the islets. Soluble mediators produced by the activated macrophages such as interleukin-1Beta, tumor necrosis factor-alpha, and nitric oxide play a critical role in the destruction of residual beta cells. KRV causes autoimmune type 1 diabetes in diabetes resistant-BioBreeding rats by breakdown of immune balance, including the preferential activation of effector T cells, such as Th1-like CD45RC+CD4+ T cells and CD8+ T cells, and down-regulation of Th2-like CD45RC-CD4+ and CD4+CD25+ T cells, rather than by direct infection of pancreatic beta cells.

Type 1 diabetes results from the destruction of insulin-producing pancreatic β-cells by a β-cell–specific autoimmune process. Although converting other cell types into insulin-producing cells may compensate for the loss of the β-cell mass while evading β-cell–specific T-cell responses, proof-of-principle of this approach in large animal models is lacking. This investigation was initiated to determine whether an insulin-producing human hepatocyte line can control diabetes when transplanted into totally pancreatectomized diabetic pigs. We established a reversibly immortalized human hepatocyte line, YOCK-13, by transferring a human telomerase reverse transcriptase cDNA and a drug-inducible Cre recombinase cassette, followed by cDNA for a modified insulin under the control of the l-type pyruvate kinase (l-PK) promoter. YOCK-13 cells produced small amounts of modified insulin and no detectable endogenous l-PK at low glucose concentrations, whereas they produced large amounts of both modified insulin and l-PK in response to high glucose concentrations. Xenotransplantation of YOCK-13 cells via the portal vein into immunosuppressed, totally pancreatectomized pigs decreased hyperglycemia and prolonged survival without adverse effects such as portal thrombosis, liver necrosis, pulmonary embolism, and tumor development. We suggest that this reversibly immortalized, insulin-secreting human hepatocyte line may overcome the shortage of donor pancreata for islet transplantation into patients with type 1 diabetes.