Effects of lobeglitazone, a novel thiazolidinedione, on adipose tissue remodeling and brown and beige adipose tissue development in db/db mice.

BACKGROUND/OBJECTIVES: We investigated the effect of long-term treatment with lobeglitazone, a novel thiazolidinedione-based activator of peroxisome proliferator-activated receptor gamma, on adipose tissue (AT), focusing on its effects on insulin resistance in obese db/db mice. METHODS: Seven-week-old male db/db mice were assigned to either a vehicle-treated (n=8) or lobeglitazone-treated (n=8) group. Lobeglitazone (1 mg kg-1 daily) was injected intraperitoneally for 20 weeks. RESULTS: Lobeglitazone treatment for 20 weeks resulted in a remarkably improved glycemic index, including significantly decreased glucose levels, enhanced insulin sensitivity and preserved pancreatic beta cells. Both whole body and subcutaneous AT weight increased in the lobeglitazone-treated group. However, lobeglitazone induced an increase in the number of small adipocyte in both epididymal and subcutaneous AT, with a significant weight decrease in the epididymal AT of db/db mice. Using flow cytometry, the CD11c-positive M1 macrophages and CD206-positive M2 macrophages in the epididymal AT were observed to exhibit a decreased M1-to-M2 ratio in lobeglitazone-treated db/db mice. Furthermore, in the lobeglitazone-treated group, interscapular brown AT was clearly visualized by 18F-fluoro-2-deoxy-D-glucose positron emission tomography combined with computed tomography (18F-FDG-PET/CT) and its mass was significantly greater than that of the vehicle-treated group. In the lobeglitazone-treated group, beige-specific gene expression and the number of mitochondria in white AT were upregulated. Lobeglitazone, with upregulating interferon regulatory factor-4 (a key transcriptional regulator of thermogenesis), promoted the development of brown adipocytes and the differentiation of white adipocytes into beige adipocytes. CONCLUSIONS: Long-term lobeglitazone treatment has a beneficial role in remodeling and ameliorating inflammation in white AT and in glycemic control, in relation to insulin sensitivity in obese db/db mice. Moreover, lobeglitazone induced the differentiation of brown and beige adipocytes. Collectively, our data suggest that lobeglitazone treatment provides promising effects on white and brown AT as well as great improvement in glycemic control, as a potent insulin sensitizer.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK.

BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

Case-matched comparison of ABO-incompatible and ABO-compatible living donor liver transplantation.

BACKGROUND: ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and patient survival between ABO-compatible (ABO-C) and ABO-I LDLT. The aim was to compare the outcomes of ABO-I LDLT with those of ABO-C LDLT using the matched-pairs method. METHODS: Patients who underwent ABO-I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO-C LDLT (1:2 matching). RESULTS: Forty-seven ABO-I LDLT procedures were included. Ninety-four patients who had ABO-C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO-I LDLT and ABO-C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody-mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO-I and ABO-C groups (P = 0.478 and P = 0.511 respectively). Three patients who had ABO-I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1-, 2- and 3-year patient survival rates after ABO-I LDLT and ABO-C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively. CONCLUSION: The short-term outcomes of ABO-I LDLT were comparable to those of ABO-C LDLT in this study. ABO-I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.

Identification of a novel HLA-B*40 variant allele, B*40:301, by sequence-based typing.

The new allele, HLA-B*40:301 differs from B*40:01:02 by one nucleotide substitution at codon 239 (AGA → AAA).

Identification of a novel HLA-C*03 variant allele, C*03:280 by sequence-based typing.

The new allele, HLA-C*03:280 differs from C*03:04:01 by one nucleotide substitution at codon 35 (CGG→CAG).

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

A new HLA-A*30 allele, A*30:81, identified by sequence-based typing.

The new allele, HLA-A*30:81, differs from A*30:01:01 by one nucleotide substitution at codon 272 (CTG→ATG).

Incidence and risk factors of poor mobilization in adult autologous peripheral blood stem cell transplantation: a single-centre experience.

BACKGROUND AND OBJECTIVES: Collection of sufficient CD34+ cells for autologous peripheral blood stem cell (PBSC) transplantation is frequently failed in patients with lymphoma or multiple myeloma (MM). We investigated the incidence and the predictive factors for poor mobilization. MATERIALS AND METHODS: A total of 205 adult patients (101 lymphoma and 104 MM) were retrospectively included for identifying the incidence of mobilization failure and the predictive factors for poor mobilization in conventional G-CSF-based mobilization regimen. Another 17 patients who used plerixafor for mobilization were included. RESULTS: Overall, 14·1% of patients (21·8% of patients with lymphoma, 6·7% of patients with MM) were poor mobilizers. Univariate analysis and multivariate analysis revealed an interval from G-CSF administration to PBSC collection exceeding 10 days and peripheral blood mononuclear cells count on the first day of collection were predictive factors for poor mobilization in lymphoma, but not in MM. Among plerixafor-treated patient group, 9 of 11 poor mobilizers who received second-cycle plerixafor mobilization were able to collect higher number of CD34+ cells than that of CD34+ cells during the G-CSF-based first mobilization. All patients who had received initial plerixafor mobilization reached 2·0 × 10(6) CD34+ cells/kg during the four leukaphereses. CONCLUSION: In conventional G-CSF-based mobilization, early PBSC collection after G-CSF administration might enhance CD34+ cell yield. A combination of a new mobilizing agent, plerixafor, would be helpful to harvest sufficient number of CD34+ cells for successful transplantation outcome while reducing the effort of collection procedures in poor mobilizers.

The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.

BACKGROUND: Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients. METHODS: Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up. RESULTS: In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively. CONCLUSION: This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.

The novel allele HLA-C*03:04:36 identified by sequence-based typing.

The new allele, HLA-C*03:04:36, differs from C*03:04:01:01 by one nucleotide substitution at codon 207 (GGC→GGT).

Frequencies of 10 autosomal minor histocompatibility antigens in Korean population and estimated disparities in unrelated hematopoietic stem cell transplantation.

Disparity of minor histocompatibility antigens (mHAs) is known to induce graft-versus-tumor and graft-versus-host disease reactions in stem cell transplantation. Not much information is available on genotypic and phenotypic distributions of the currently identified mHAs, especially in Korean population. Therefore, we report genotype and phenotype frequency analyses of 10 autosomal mHAs in 329 unrelated healthy Koreans using the Sequenom MassARRAY matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) system and polymerase chain reaction-sequence specific primers (PCR-SSP). Estimates of the probability of immunogenic mismatches between donor/recipient pairs were made from observed phenotypic frequencies. HA-1 was the most favorable mHA for clinical application with the highest disparity of 7.0%. Similar results were obtained in ACC-1. The Korean population can benefit the most in a setting of matched major histocompatibility complex (MHC)-restricted mHAs-mismatched unrelated hematopoietic stem cell transplantations with the disparity rate of 27.5% with eight hematopoietic mHAs. This is the first comprehensive report on the genotypic and phenotypic frequency distributions of human mHAs in the Korean population. It can contribute to not only donor selection before transplantation but also therapeutic approaches after transplantation. It is expected that mHA-based immunotherapy will lead to a new treatment modality tailored for patients at high risk of relapse following allogeneic hematopoietic cell transplantation.

Demethylation analysis of the FOXP3 locus shows quantitative defects of regulatory T cells in IPEX-like syndrome.

Immune dysregulation, Polyendocrinopathy, Enteropathy X-linked (IPEX) syndrome is a unique example of primary immunodeficiency characterized by autoimmune manifestations due to defective regulatory T (Treg) cells, in the presence of FOXP3 mutations. However, autoimmune symptoms phenotypically resembling IPEX often occur in the absence of detectable FOXP3 mutations. The cause of this "IPEX-like" syndrome presently remains unclear. To investigate whether a defect in Treg cells sustains the immunological dysregulation in IPEX-like patients, we measured the amount of peripheral Treg cells within the CD3(+) T cells by analysing demethylation of the Treg cell-Specific-Demethylated-Region (TSDR) in the FOXP3 locus and demethylation of the T cell-Specific-Demethylated-Region (TLSDR) in the CD3 locus, highly specific markers for stable Treg cells and overall T cells, respectively. TSDR demethylation analysis, alone or normalized for the total T cells, showed that the amount of peripheral Treg cells in a cohort of IPEX-like patients was significantly reduced, as compared to both healthy subjects and unrelated disease controls. This reduction could not be displayed by flow cytometric analysis, showing highly variable percentages of FOXP3(+) and CD25(+)FOXP3(+) T cells. These data provide evidence that a quantitative defect of Treg cells could be considered a common biological hallmark of IPEX-like syndrome. Since Treg cell suppressive function was not impaired, we propose that this reduction per se could sustain autoimmunity.

Reduction in glycated albumin can predict change in HbA1c: comparison of oral hypoglycaemic agent and insulin treatments.

AIM: To investigate whether the change in glycated albumin 3 weeks after initiating anti-diabetes treatment (oral hypoglycaemic agent or insulin) could predict the corresponding change in HbA(1c) 3 months later in Korean patients with Type 2 diabetes. METHODS: A total of 140 patients were enrolled into two groups: group I (insulin-based; n = 100) and group II (oral hypoglycaemic agent-based; n = 40). Both glycated albumin and HbA(1c) levels were measured as 'glucose control markers' during hospitalization. Glycated albumin was measured again at 3 weeks (first visit) after the initial measurement, and HbA(1c) was measured at 3 months (second visit) after the initial measurement.. The change in glucose control marker was defined as 100 × (follow-up glucose control marker--hospital glucose control marker)/hospital glucose control marker. RESULTS: In both groups, the change in glycated albumin at the first visit and in HbA(1c) at the second visit showed a moderate linear relationship (r = 0.735; P < 0.01). In group II (r = 0.778; P < 0.01), a slightly stronger linear relationship was demonstrated than in group I (r = 0.738; P < 0.001); however, there was no statistically significant difference between the two groups. A correlation coefficient between the change in glycated albumin and HbA(1c) was not affected by sex, age, BMI, haemoglobin, serum creatinine or albumin. CONCLUSION: The reduction in glycated albumin 3 weeks after the initiation of treatment corresponded with the reduction in HbA(1c) 3 months after starting treatment in both the group treated with a oral hypoglycaemic agent and the insulin-treated group of Korean patients with Type 2 diabetes.

Evaluation of overnight storage conditions for autologous peripheral blood stem cell products: comparison of three different conditions.

BACKGROUND: Overnight (ON) storage of peripheral blood stem cell (PBSC) occurs frequently in clinical settings. However, there are no standard guidelines for optimal storage conditions of freshly harvested PBSC. The aim of this study was to investigate the influence of storage temperatures on the quality of autologous PBSC and establish optimal storage conditions before cryopreservation. METHODS: A retrospective analysis was performed on 260 PBSC harvests according to pre-cryopreservation conditions: immediate processing or ON storage at room temperature (RT). For direct comparison, 30 autologous PBSC products were collected prospectively and prepared under three different pre-cryopreservation conditions: immediate processing, ON storage at 4°C and ON storage at RT. The recovery of CD34(+) cells, post-thaw CFU-GM count and viability were analysed. RESULTS: Retrospective analysis revealed that post-thaw CFU-GM count was significantly lower when PBSC were stored ON at RT compared to when immediately processed (136·4 vs. 409·6/µl). Prospective analysis showed a mean recovery of CD34(+) cells of 65·5 ± 25·1%, 70·5 ± 27·4% and 35·9 ± 25·1% for immediate processing, ON storage at 4°C and ON storage at RT, respectively. Similarly, mean viability and CFU-GM counts were significantly reduced when stored ON at RT compared to when immediately processed or stored ON at 4°C (60·4 ± 25·6 vs. 84·1 ± 12·9 vs. 82·7 ± 12·6%, 15·7 ± 25·7 vs. 398·5 ± 906·2 vs. 350·0 ± 847·9/µl, respectively). CONCLUSIONS: ON storage of autologous PBSC at RT significantly decreased the quality of HPCs. These data indicate that ON storage of autologous PBSC at 4°C would be the most reasonable approach for maintaining the quality of HPCs when immediate processing is not possible.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

BACKGROUND: With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy. METHODS: The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed. RESULTS: From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14%; P=0.04), and less severe hepatitis (0 vs 17%; P=0.002). CONCLUSION: Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion.

SLC30A8 encodes the ß-cell-specific zinc transporter-8 (ZnT-8) expressed in insulin secretory granules. The single-nucleotide polymorphism rs13266634 of SLC30A8 is associated with susceptibility to post-transplantation diabetes mellitus (PTDM). We tested the hypothesis that the polymorphic residue at position 325 of ZnT-8 determines the susceptibility to cyclosporin A (CsA) suppression of insulin secretion. INS (insulinoma)-1E cells expressing the W325 variant showed enhanced glucose-stimulated insulin secretion (GSIS) and were less sensitive to CsA suppression of GSIS. A reduced number of insulin granule fusion events accompanied the decrease in insulin secretion in CsA-treated cells expressing ZnT-8 R325; however, ZnT-8 W325-expressing cells exhibited resistance to the dampening of insulin granule fusion by CsA, and transported zinc ions into secretory vesicles more efficiently. Both tacrolimus and rapamycin caused similar suppression of GSIS in cells expressing ZnT-8 R325. However, cells expressing ZnT-8 W325 were resistant to tacrolimus, but not to rapamycin. The Down's syndrome candidate region-1 (DSCR1), an endogenous calcineurin inhibitor, overexpression and subsequent calcineurin inhibition significantly reduced GSIS in cells expressing the R325 but not the W325 variant, suggesting that differing susceptibility to CsA may be due to different interactions with calcineurin. These data suggest that the ZnT-8 W325 variant is protective against CsA-induced suppression of insulin secretion. Tolerance of ZnT-8 W325 to calcineurin activity may account for its protective effect in PTDM.

Effect of ABCA1 variant on atherogenic dyslipidaemia in patients with Type 2 diabetes treated with rosiglitazone.

AIMS: To investigate the effect of two common ATP-binding cassette transporter 1 (ABCA1) polymorphisms (rs4149263 and rs2020927) on atherogenic dyslipidaemia in Korean Type 2 diabetic patients who were treated with rosiglitazone. PATIENTS AND METHODS: Two hundred and fifty-six patients with Type 2 diabetes who had never previously received peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists or lipid-lowering treatment were treated with 4 mg of rosiglitazone daily for 12 weeks without any adjustment to their glucose-lowering regimen. The primary outcome was the change in atherogenic index of plasma (AIP), calculated as log [triglyceride (mmol/l)/high-density lipoprotein cholesterol (mmol/l)], before and after rosiglitazone treatment. The effect of rosiglitazone on the change in AIP was compared across the ABCA1 single nucleotide polymorphisms (SNPs) rs41429263 and rs2020927. RESULTS: Before adjustment, the change in AIP at 12 weeks was significantly different across the rs4149263 genotypes [median (interquartile range): -0.05 (-0.21, 0.09) for TT; 0.02 (-0.09, 0.17) for TC; and 0.11 (0.03, 0.25) for CC; P = 0.003], but not across the rs2020927 [-0.04 (-0.18, 0.10) for TT; 0.03 (-0.17, 0.15) for TC; and -0.03 (-0.13, 0.10) for CC; P = 0.401]. After controlling for age, gender and duration of diabetes, the presence of the C-allele was significantly associated with an increase in AIP by 0.13 [95% confidence interval (CI), 0.04-0.21; P = 0.003]. This association did not change significantly when body mass index and pretreatment metabolic parameters were additionally controlled for (the change in AIP: 0.14; 95% CI, 0.04-0.24; P = 0.007). CONCLUSIONS: The ABCA1 SNP rs4149263 may be associated with the change in atherogenic lipid profile in Type 2 diabetes treated with rosiglitazone.

Interaction between fatness and fitness on CVD risk factors in Asian youth.

The purpose of this study was to investigate the effects of fatness and fitness on insulin resistance (IR) and cardiovascular disease (CVD) risk factors among Korean adolescents. A total of 322 male high school students participated Departme nt of Sport and Leisure Studies, Yonsei University, Seoup, Republic of Korea Department of Sport and Leisure Studies, Yonsei University, Seoup, Republic of Korea in the cross-sectional part of the study. To determine the interaction of fatness and fitness levels on IR and CVD risk factors, subjects were stratified into four groups based on their body mass index (BMI) and cardio-respiratory fitness. Subjects who were in the high-fat category had significantly higher IR and CVD risk score than subjects in the low-fat category regardless of their fitness level. Subjects who were in high-fat-high-fit group showed significantly lower IR and CVD risk score than high-fat-low-fit group. Twenty-nine obese and unfit subjects participated in the intervention study. Twelve weeks of exercise training significantly reduced body weight (4.11+/-0.75 kg) and improved VO(2max) which resulted in a significant improvement in IR and CVD risk score (2.16+/-0.62 vs. 0.20+/-0.75). Interestingly, improvement in cardio-respiratory fitness and small reduction in body weight in relatively short-term significantly reduced the CVD risk score to the level of low-fat-low-fit subjects. Our results show the importance of fitness in determining IR and CVD risk factors among obese adolescents.

Sarcopenia is associated with the risk of significant liver fibrosis in metabolically unhealthy subjects with chronic hepatitis B.

BACKGROUND: Sarcopenia is significantly associated with the degree of liver fibrosis. This study investigated the influence of sarcopenia on liver fibrosis in individuals with chronic hepatitis B. METHODS: Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analysed. The sarcopenia index (total appendicular skeletal muscle mass [kg]/body mass index [kg/m2 ]) was calculated using dual-energy X-ray absorptiometry. Sarcopenia was defined as the lowest quintile sarcopenia index value (cut-offs: 0.89 for men and 0.58 for women). The fibrotic burden was assessed using the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index. Significant fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile and a fibrosis-4 index ≥2.67. RESULTS: Among the 506 respondents with chronic hepatitis B (258 men and 248 women), the nonalcoholic fatty liver disease fibrosis score and fibrosis-4 index identified sarcopenia and significant fibrosis in 126 (24.9%) and 217 (42.9%), respectively. Sarcopenia was significantly associated with significant fibrosis, regardless of the fibrosis prediction model used (all P < 0.05). When the study population was stratified according to metabolic factors, sarcopenia was specifically associated with an increased risk of significant fibrosis among subgroups with obesity, insulin resistance, metabolic syndrome and liver steatosis (odds ratio 2.37-3.57; all P < 0.05). An independent association between sarcopenia and significant fibrosis was identified after adjusting for other confounders (odds ratio 2.67-3.62 by the nonalcoholic fatty liver disease fibrosis score and 2.04-2.62 by the fibrosis-4 index; all P < 0.05). CONCLUSIONS: Sarcopenia is associated with significant fibrosis in subjects with chronic hepatitis B, specifically those with obesity, insulin resistance, metabolic syndrome and liver steatosis.