Efficacy and safety of lobeglitazone versus sitagliptin as an add-on to metformin in patients with type 2 diabetes with two or more components of metabolic syndrome over 24 weeks.

We aimed to evaluate the efficacy and safety profile of lobeglitazone compared with sitagliptin as an add-on to metformin in patients with type 2 diabetes as well as other components of metabolic syndrome. Patients inadequately controlled by metformin were randomly assigned to lobeglitazone (0.5 mg, n = 121) or sitagliptin (100 mg, n = 126) for 24 weeks. The mean changes in HbA1c of the lobeglitazone and sitagliptin groups were -0.79% and -0.86%, respectively; the between-group difference was 0.08% (95% confidence interval, -0.14% to 0.30%), showing non-inferiority. The proportion of patients having two or more factors of other metabolic syndrome components decreased to a greater extent in the lobeglitazone group than in the sitagliptin group (-11.9% vs. -4.8%; P < .0174). Favourable changes in the lipid metabolism were also observed with lobeglitazone, which had a similar safety profile to sitagliptin. Lobeglitazone was comparable with sitagliptin as an add-on to metformin in terms of efficacy and safety.

Melatonin improves insulin resistance and hepatic steatosis through attenuation of alpha-2-HS-glycoprotein.

Melatonin plays an important role in regulating circadian rhythms. It also acts as a potent antioxidant and regulates glucose and lipid metabolism, although the exact action mechanism is not clear. The α2-HS-glycoprotein gene (AHSG) and its protein, fetuin-A (FETUA), are one of the hepatokines and are known to be associated with insulin resistance and type 2 diabetes. The aim of this study was to determine whether melatonin improves hepatic insulin resistance and hepatic steatosis in a FETUA-dependent manner. In HepG2 cells treated with 300 µmol/L of palmitic acid, phosphorylated AKT expression decreased, and FETUA expression increased, but this effect was inhibited by treatment with 10 µmol/L of melatonin. However, melatonin did not improve insulin resistance in FETUA-overexpressing cells, indicating that improvement in insulin resistance by melatonin was dependent on downregulation of FETUA. Moreover, melatonin decreased palmitic acid-induced ER stress markers, CHOP, Bip, ATF-6, XBP-1, ATF-4, and PERK. In addition, in the high-fat diet (HFD) mice, oral treatment with 100 mg/kg/day melatonin for 10 weeks reduced body weight gain to one-third of that of the HFD group and hepatic steatosis. Insulin sensitivity and glucose intolerance improved with the upregulation of muscle p-AKT protein expression. FETUA expression and ER stress markers in the liver and serum of HFD mice were decreased by melatonin treatment. In conclusion, melatonin can improve hepatic insulin resistance and hepatic steatosis through reduction in ER stress and the resultant AHSG expression.

Knockdown of sestrin2 increases pro-inflammatory reactions and ER stress in the endothelium via an AMPK dependent mechanism.

BACKGROUND & OBJECTIVE: Sestrin2 (sesn2) has recently gained attention as an important regulator for various metabolic disorders. Sesn2 is involved in AMP-activated protein kinase (AMPK) activation, which leads to anti-inflammatory and anti-oxidative responses. However, the role of sesn2 in the endothelium has not yet been clarified. METHODS: To evaluate sesn2-mediated anti-atherosclerotic effects, siRNA to silence sesn2 expression was introduced to human umbilical vein endothelial cells (HUVECs), THP-1 cells and C57BL/6 mice. Lipopolysaccharide (LPS) was administrated to sesn2-knockdown cells and mice to induce atherosclerotic signals. RESULTS: Knockdown of sesn2 was involved with atherosclerotic reactions caused by LPS treatment through decrease of AMPK phosphorylation. In sesn2-knockdown HUVECs and THP-1 cells, LPS-mediated nuclear factor kappa B (NF-κB) phosphorylation and secretion of pro-inflammatory cytokines were both significantly increased. In HUVECs, expression of adhesion molecules and LPS-stimulated adhesion of THP-1 cells to the endothelium were significantly increased after sesn2-knockdown. Furthermore, LPS-induced reactive oxygen species (ROS) production, endoplasmic reticulum (ER) stress, and cell toxicity were all significantly elevated after sesn2-knockdown in HUVECs. Interestingly, all these pro-atherosclerotic effects were fully abrogated by treatment with an AMPK activator. In aortic tissue samples from C57BL/6 mice, sesn2-knockdown using siRNA oligomers resulted in reduced AMPK phosphorylation and induction of LPS-mediated NF-κB phosphorylation, leading to up-regulation of adhesion molecules and ER stress-related signaling. CONCLUSION: Knockdown of sesn2 aggravates atherosclerotic processes by increasing pro-inflammatory reactions and ER stress in the endothelium via an AMPK-dependent mechanism, suggesting that sesn2 might be a novel therapeutic target for atherosclerosis.

The synergistic impact of nonalcoholic fatty liver disease and metabolic syndrome on subclinical atherosclerosis.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a well-known contributor for the development of cardiovascular disease (CVD). We examined the influence of NAFLD and metabolic syndrome (MetS) on markers of subclinical atherosclerosis, including carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial pressure index (ABI), after adjusting for cardiometabolic risk factors. DESIGN: A cross-sectional study. PATIENTS AND MEASUREMENTS: The association between NAFLD, MetS and markers of subclinical atherosclerosis was assessed in 955 participants without CVD using multiple logistic regression analysis after adjusting for multiple cardiometabolic risk variables. RESULTS: After adjusting for age and sex, CIMT and baPWV were found to be significantly correlated with multiple cardiometabolic risk variables, whereas ABI was only associated with obesity parameters. The prevalence of NAFLD differed significantly according to the presence of subclinical atherosclerosis as defined by both CIMT and baPWV (P = 0·004 and P = 0·007, respectively). After adjusting for potential confounding factors, NAFLD or MetS was not associated with subclinical atherosclerosis as defined by CIMT and baPWV. However, individuals with both NAFLD and MetS had a significantly higher risk of subclinical atherosclerosis as defined by CIMT (OR = 2·06, 95% CI = 1·13-3·74) or baPWV (OR = 2·64, 95% CI = 1·46-4·76) compared to normal subjects, even after adjusting for potential confounders. CONCLUSIONS: The results show that NAFLD and MetS have a synergistic impact on the subclinical atherosclerosis, which suggests that individuals with both NAFLD and MetS should be strongly advised to engage in CVD prevention strategies.

Circulating angiopoietin-like protein 8 (ANGPTL8) and ANGPTL3 concentrations in relation to anthropometric and metabolic profiles in Korean children: a prospective cohort study.

BACKGROUND: Previous studies have shown that angiopoietin-like protein 8 (ANGPTL8), also called as betatrophin, acts together with ANGPTL3 to regulate lipid metabolism, glucose metabolism, and energy homeostasis. Moreover, ANGPTL8 promotes proliferation of pancreatic ß-cells and induces insulin secretion. However, there are no previous longitudinal studies in humans. METHODS: We analyzed the age- and sex-matched data of 240 normal weight and overweight Korean children from the Korean Metabolic disorders and Obesity Study in Elementary School children (K-MOSES), a prospective observational cohort study. RESULTS: At baseline, ANGPTL8 concentrations were positively associated with triglycerides (TG) (r = 0.168, P = 0.010), whereas ANGPTL3 levels were associated with fasting insulin (r = 0.248, P < 0.001) and the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.197, P = 0.002). Although both ANGPTL8 and ANGPTL3 levels did not differ between children with normal weight and children with overweight, ANGPTL8 levels were increased in males compared to females (341.2 [267.4-436.5] vs. 270.2 [213.9-378.8] pg/ml, P = 0.001). In particular, there was no significant inter-relationship between circulating ANGPTL8 and ANGPTL3 concentrations in Korean boys and girls (r = -0.073, P = 0.265). Multivariate analysis showed that baseline ANGPTL8 concentrations were independently associated with future changes of serum TG levels in Korean children after adjusting for confounding factors after a 3 year follow-up period (r = -0.165, P = 0.016). CONCLUSIONS: This longitudinal study demonstrated for the first time that baseline ANGPTL8 levels were associated with baseline and future changes in TG levels in Korean children.

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P < 0.01). In the L-carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P < 0.05). Both the PFS and MFS were significantly improved in patients younger than 50 years and those with free T3 ≥ 4.0 pg/mL by treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.

Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study.

UNLABELLED: Previous studies have shown that nonalcoholic fatty liver disease (NAFLD) and sarcopenia may share pathophysiological mechanisms, such as insulin resistance, inflammation, vitamin D deficiency, and decreased physical activity. However, their direct relationship has not been investigated. The association between NAFLD and sarcopenia was examined in 452 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. The liver attenuation index (LAI), which was measured using abdominal computed tomography (CT), was used as a parameter for the diagnosis of NAFLD. Sarcopenia was defined using a skeletal muscle mass index (SMI) [SMI (%) = total skeletal muscle mass (kg) / weight (kg) × 100] that was measured by dual energy X-ray absorptiometry (DXA). After adjusting for age and sex, both SMI and LAI were negatively correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) (P < 0.001) and high sensitivity C-reactive protein (hsCRP) (P < 0.001) as well as brachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness. Furthermore, SMI and LAI had positive relationships with high-density lipoprotein (HDL)-cholesterol, but both had a negative relationship with triglyceride, alanine aminotransferase (ALT), and total body fat. In a multiple logistic regression analysis, the odds ratio for NAFLD risk was 5.16 (95% confidence interval [CI] = 1.63-16.33) in the lowest quartile of SMI compared to the highest after adjusting for potential confounding factors. CONCLUSION: Individuals with lower muscle mass exhibited increased risk of NAFLD. This result may provide a novel insight into the mechanism linking between sarcopenia and NAFLD. (Clinical trial no. NCT01594710.)

HIF-1α expression as a protective strategy of HepG2 cells against fatty acid-induced toxicity.

Free fatty acid-induced lipotoxicity via increased endoplasmic reticulum (ER) stress and hepatocyte apoptosis is a key pathological mechanism of non-alcoholic steatohepatitis. A role of hypoxia-inducible factor 1α (HIF-1α) in this process has been suggested, but direct evidence is lacking. Here, we used HepG2 cells as a model to study whether HIF-1α can reduce palmitic acid-induced lipotoxicity and ER stress. In HepG2 cells treated with 500 µM palmitic acid, HIF-1α expression increased transiently, the decline was associated with increased cleaved caspase-3 expression. Overexpression and knockdown of HIF-1α decreased and exacerbated, respectively, palmitic acid-induced lipoapoptosis. The overexpression also blunted upregulation of the ER stress markers, C/EBP homologous protein (CHOP) and chaperone immunoglobulin heavy chain binding protein (Bip), while the knockdown increased the level of CHOP. In line with this, CHOP promoter activity decreased following HIF-1α binding to the CHOP promoter hypoxia response element. These results indicate that hepatocyte lipotoxicity is associated with decreased HIF-1α expression. It also suggests that upregulation of HIF-1α can be a possible strategy to reduce lipotoxicity in non-alcoholic fatty liver disease.

Clinical and metabolic factors associated with development and regression of nonalcoholic fatty liver disease in nonobese subjects.

BACKGROUND & AIMS: The course of NAFLD (nonalcoholic fatty liver disease) and associated factors in nonobese subjects are not well established. We investigated contributing factors for the development and regression of NAFLD in nonobese Koreans, and whether they would differ from those of obese subjects. METHODS: Two thousand three hundred and seven adults aged over 18 years participated in this longitudinal observational study. The mean duration of follow-up was 28.7 (±13.2) months. The participants were divided into two groups according to the baseline BMI (nonobese group: BMI <25 kg/m(2), obese group: BMI ≥25 kg/m(2)). The presence or absence of NAFLD was assessed by abdominal ultrasonography. RESULTS: Body weight change was independently associated with both the development and regression of NAFLD in nonobese subjects as well as obese subjects. Among the subjects who developed NAFLD, the amount of weight change was higher in nonobese subjects compared to obese subjects (1.6 ± 3.9% vs 0.6 ± 4.2%, P = 0.022); and among those who showed regression of NAFLD, the amount of weight change was lower in nonobese subjects (-1.9 ± 4.0% vs -5.0 ± 4.6%, P < 0.001). Among all the components of metabolic syndrome, only high triglyceride levels (>150 mg/dl) at the baseline were significantly associated with both the development and regression of NAFLD in nonobese subjects (ORs, 1.54 (1.10-2.14), and 0.60 (0.38-0.96) respectively). CONCLUSION: Body weight change and baseline triglyceride levels were strong indicators for the development and regression of NAFLD in a nonobese population.

Comparison of acarbose and voglibose in diabetes patients who are inadequately controlled with basal insulin treatment: randomized, parallel, open-label, active-controlled study.

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% ± 0.71% to 7.71% ± 0.93%) and voglibose groups (from 8.38% ± 0.73% to 7.68% ± 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 ± 69.38 to 176.80 ± 46.63 mg/dL) compared with the voglibose group (from 224.18 ± 70.07 to 193.01 ± 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528).

Higher mortality in metabolically obese normal-weight people than in metabolically healthy obese subjects in elderly Koreans.

OBJECTIVE: The purpose of this study was to investigate the impact of body mass index (BMI) and the presence of metabolic syndrome (MetS) on all-cause and cardiovascular mortality in elderly Korean men and women, and especially to compare metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) subjects. PATIENTS AND METHODS: A total of 2317 elderly people (over 60 years of age) were studied using follow-up data from the South-West Seoul (SWS) Study, a prospective cohort study. Mortality from all causes and cardiovascular disease (CVD) were evaluated according to the combination of the presence or absence of MetS and Asian-specific body mass index (BMI) criteria (BMI <23 kg/m²; normal weight, BMI 23-24·9 kg/m²; overweight, BMI ≥25 kg/m²; obesity). RESULTS: During a median follow-up of 10·3 years, 393 subjects died, including 126 from CVD. Among subjects with MetS, all-cause and CVD mortality were significantly higher in normal-weight subjects than overweight or obese individuals in Cox proportional-hazard models adjusted for confounding factors. Furthermore, among six groups with various MetS/BMI combinations, MONW individuals had the highest risk, whereas overweight subjects without MetS had the lowest risk of death from all causes and CVD [HR = 2·2 (95% CI = 1·4-3·4), HR = 3·0 (95% CI = 1·4-6·6) respectively]. Interestingly, all-cause mortality was significantly higher in MONW than MHO individuals. CONCLUSIONS: In contrast to MHO subjects, elderly individuals with the MONW phenotype exhibited greater all-cause mortality during 10 years of follow-up.

Relationships between sarcopenic obesity and insulin resistance, inflammation, and vitamin D status: the Korean Sarcopenic Obesity Study.

OBJECTIVE: It has been suggested that insulin resistance, low-grade inflammation and vitamin D deficiency are associated with obesity and sarcopenia. However, their relationships with sarcopenic obesity (SO) are unclear. We evaluated the impact of homoeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D (25[OH]D) levels on SO in Korean adults. STUDY SUBJECT/MEASUREMENTS: This study included 493 apparently healthy adults (180 men and 313 women) enrolled in the Korean Sarcopenic Obesity Study. Sarcopenia was defined as a skeletal muscle mass index (SMI) of 1 SD below the sex-specific mean value for a young reference group. Obesity was defined as a visceral fat area (VFA) ≥100 cm(2) . We classified the participants into four sarcopenia/obesity groups based on both SMI and VFA. RESULTS: The prevalence of SO was 17·8% in men and 24·9% in women. In women, the SO group had higher HOMA-IR and hsCRP levels compared with the non-SO group. In men, the 25[OH]D levels were significantly lower in the SO group than the non-SO group. Both hsCRP and HOMA-IR levels were negatively correlated with SMI and positively correlated with VFA in both men and women, whereas 25[OH]D levels were positively correlated with SMI in both men and women. Multiple binary logistic regression analysis showed that HOMA-IR and 25[OH]D levels were independently associated with SO in men, while HOMA-IR and hsCRP were significant factors predicting SO in women. CONCLUSION: Insulin resistance, inflammation and vitamin D deficiency were associated with SO in a Korean adult population.

The effects of caloric restriction on fetuin-A and cardiovascular risk factors in rats and humans: a randomized controlled trial.

OBJECTIVES: The liver-secreted protein fetuin-A is associated with insulin resistance, metabolic syndrome, type 2 diabetes and atherosclerosis. We examined the effect of caloric restriction (CR) on fetuin-A levels and concomitant changes in hepatic steatosis and cardiovascular risk factors in rats and humans. DESIGN AND SUBJECTS: We performed a randomized, controlled clinical trial to examine circulating fetuin-A levels and cardiovascular risk parameters including visceral fat area (VFA), atherogenic lipid profile, inflammatory markers, adipokines levels and brachial artery endothelial function in 76 overweight women with type 2 diabetes before and after 12 weeks of CR. In addition, the effects of CR on hepatic steatosis and fetuin-A mRNA expression were evaluated in Otuska Long Evans Tokushima Fatty (OLETF) rats, an animal model of obesity and type 2 diabetes. RESULTS: Circulating fetuin-A levels were significantly decreased after 12 weeks of CR and were accompanied by improvements in VFA, blood pressure, glucose, lipid profiles and liver function. The CR group also showed a significant decrease in apolipoprotein B, leptin and insulin resistance compared to those in the control group, although endothelial function was not different. Multiple regression analysis showed that the changes in fetuin-A levels were independently associated with CR and changes in hsCRP and adiponectin (R² = 0·156). Moreover, CR significantly reduced hepatic steatosis and fetuin-A expression, as well as weight, glucose, total cholesterol and triglyceride levels, in OLETF rats. CONCLUSION: Caloric restriction significantly reduced the hepatic expression of fetuin-A and its circulating levels and improved several cardiovascular risk factors in obese rats and humans with type 2 diabetes.

The differential relationship between fat mass and bone mineral density by gender and menopausal status.

Osteoporosis and obesity are important public health problems in an aging society. We investigated the differential impacts of fat on bone mineral density (BMD) according to gender and menopausal status. We analyzed the baseline data of an ongoing observational cohort study, including a total of 502 healthy subjects 20-88 years of age (144 men, 159 premenopausal women, 199 postmenopausal women). Body composition and fat mass were measured using computed tomography and dual energy X-ray absorptiometry (DXA). BMD was measured at lumbar spines using DXA. In men and postmenopausal women, there was no significant correlation between fat and bone parameters after adjusting for age and body weight. However, in premenopausal women, BMD had significant negative correlations with waist circumference, total fat area, subcutaneous fat area, appendicular fat mass and percentage fat mass after adjusting for age and body weight. Furthermore, only in premenopausal women, the subjects with the highest quartile of percentage fat mass had the lowest BMD even after adjusting for confounding factors including age, body weight, physical activity, alcohol use and smoking history. Multiple linear regression analysis showed that percentage fat mass was a significant negative decisive factor for BMD in premenopausal women. Our study showed the differential relationship between fat mass and BMD according to gender and menopausal status. Only in premenopausal women did fat mass have a significant negative effect on bone mass. This result suggests the importance of reducing fat mass in order to achieve peak bone mass in young adult women.

Association of adiponectin, resistin, and vascular inflammation: analysis with 18F-fluorodeoxyglucose positron emission tomography.

OBJECTIVE: Adiponectin and resistin are adipokines that are linked to obesity, inflammation, and atherosclerosis. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography is a promising imaging technique that can be used to evaluate vascular inflammation. METHODS AND RESULTS: We measured adiponectin and resistin levels, as well as traditional cardiovascular risk factors, in 60 obese subjects and 60 nonobese controls. In addition, we compared carotid intima-media thickness and target-to-background ratio (TBR) measured using (18)F-fluorodeoxyglucose-positron emission tomography/computed tomography. The mean TBR values were significantly higher in the obese group compared with normal subjects, although their mean carotid intima-media thickness levels were not significantly different. Serum adiponectin levels showed a significant negative correlation with mean TBR values (r = -0.215, P = 0.020), whereas resistin levels were positively correlated with mean TBR values (r = 0.214, P = 0.021). Multiple linear regression analysis showed that mean TBR values were independently associated with body mass index, high-sensitivity C-reactive protein, and resistin levels (R(2) = 0.308). CONCLUSIONS: Adiponectin and resistin may be useful as biomarkers to reflect vascular inflammation. In particular, resistin levels were independently associated with vascular inflammation even after adjusting for other cardiovascular risk factors.

North Korean refugee health in South Korea (NORNS) study: study design and methods.

BACKGROUND: Understanding the health status of North Korean refugees (NKRs), and changes in health during the resettlement process, is important from both the humanitarian standpoint and the scientific perspective. The NOrth Korean Refugee health iN South Korea (NORNS) study aims to document the health status and health determinants of North Korean refugees, to observe various health outcomes as they occur while adapting to the westernized lifestyle of South Korea, and to explain the mechanisms of how health of migrants and refugees changes in the context of new environmental risks and opportunities. METHODS: The NORNS study was composed of an initial survey and a follow-up survey 3.5 years apart. Participants were recruited voluntarily among those aged 30 or more living in Seoul. The survey consists of a health questionnaire and medical examination. The health questionnaire comprises the following six domains: 1) demographic and migration information 2) disease history, 3) mental health, 4) health-related lifestyle, 5) female reproductive health, and 6) sociocultural adaptation. The medical examination comprises anthropometric measurements, blood pressure and atherosclerosis, and various biochemical measurements. Prevalence of several diseases able to be diagnosed from the medical examination, the changes between the two surveys, and the association between the outcome and other measurements, such as length of stay and extent of adaptation in South Korea will be investigated. Furthermore, the outcome will be compared to a South Korean counterpart cohort to evaluate the relative health status of NKRs. DISCUSSION: The NORNS study targeting adult NKRs in South Korea is a valuable study because various scales and medical measurements are employed for the first time. The results obtained from this study are expected to be utilized for developing a health policy for NKRs and North Korean people after unification. Additionally, since NKRs are an immigrant group who are the same race and have the same genetic characteristics as South Koreans, this study has the characteristics of a unique type of migrant health study.

Effects of the Crystalline Properties of Hollow Ceria Nanostructures on a CuO-CeO2 Catalyst in CO Oxidation.

The development of an efficient and economic catalyst with high catalytic performance is always challenging. In this study, we report the synthesis of hollow CeO2 nanostructures and the crystallinity control of a CeO2 layer used as a support material for a CuO-CeO2 catalyst in CO oxidation. The hollow CeO2 nanostructures were synthesized using a simple hydrothermal method. The crystallinity of the hollow CeO2 shell layer was controlled through thermal treatment at various temperatures. The crystallinity of hollow CeO2 was enhanced by increasing the calcination temperature, but both porosity and surface area decreased, showing an opposite trend to that of crystallinity. The crystallinity of hollow CeO2 significantly influenced both the characteristics and the catalytic performance of the corresponding hollow CuO-CeO2 (H-Cu-CeO2) catalysts. The degree of oxygen vacancy significantly decreased with the calcination temperature. H-Cu-CeO2 (HT), which presented the lowest CeO2 crystallinity, not only had a high degree of oxygen vacancy but also showed well-dispersed CuO species, while H-Cu-CeO2 (800), with well-developed crystallinity, showed low CuO dispersion. The H-Cu-CeO2 (HT) catalyst exhibited significantly enhanced catalytic activity and stability. In this study, we systemically analyzed the characteristics and catalyst performance of hollow CeO2 samples and the corresponding hollow CuO-CeO2 catalysts.

Effects of a three-month combined exercise programme on fibroblast growth factor 21 and fetuin-A levels and arterial stiffness in obese women.

OBJECTIVE: We examined the relationship between brachial-ankle pulse wave velocity (baPWV) reflecting arterial stiffness and the levels of novel hepatokines fibroblast growth factor 21 (FGF21) and fetuin-A. In addition, we evaluated the effect of a 3-month combined aerobic and resistance exercise programme on FGF21 and fetuin-A levels as well as arterial stiffness in obese women. METHODS: Forty nondiabetic, obese women (body mass index = 27·6 ± 2·4 kg/m(2) ) were included in the study and were compared before and after a 3-month exercise programme, which was composed of 45 min of aerobic exercise at an intensity of 60-75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times a week. All exercise sessions were supervised by a professional exercise physiologist. RESULTS: At baseline, baPWV levels were correlated with age, body mass index (BMI), systolic blood pressure (SBP), high density lipoprotein cholesterol, fasting glucose and serum FGF21 levels. In a multiple stepwise regression analysis using baPWV as a dependent variable, baPWV levels were associated with age, BMI, SBP, FGF21 and fetuin-A levels (R(2) = 0·744). After the exercise programme, BMI, waist circumference, SBP, diastolic blood pressure and triglyceride levels were significantly decreased. Moreover, baPWV values were significantly improved (P < 0·001) along with modest decrease in FGF21 levels (P = 0·043). However, fetuin-A levels were not changed significantly (P = 0·202). CONCLUSIONS: A 3-month combined exercise programme decreases the FGF21 levels as well as arterial stiffness in obese Korean women.

Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes.

BACKGROUND: Adipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited. METHODS: We enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP) levels, and the homeostasis model assessment of insulin resistance (HOMA-IR), as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT). RESULTS: Serum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637). Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017). CONCLUSIONS: Circulating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.