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Orostachys japonicus has traditionally been used as a food product and a fork medicine in Asia to treat various diseases. Angiogenesis is a critical process that contributes to various chronic diseases via excessive delivery of oxygen and nutrients. Common anti‐angiogenic drugs have serious problems related to high costs and side effects; thus, natural products with low costs and no cytotoxicity have garnered increasing interest. In this study, we evaluated and compared the anti‐angiogenic effects and phenolic compound contents between wild (WOEs) and cultivated O. japonicus extracts (COEs) prepared under various extract conditions. WOEs and COEs suppressed cell proliferation of human umbilical vein endothelial cells (HUVECs) and inhibited vascular endothelial growth factor‐induced chemotactic migration, invasion, and capillary‐like tube formation in HUVECs. Among COEs, that prepared by 70% EtOH (70% CE) showed the most effective anti‐angiogenic activity in HUVECs. When compared to WOEs, total polyphenol and total flavonoid contents were 1.28 to 4.38 times higher in COEs, and 70% CE contained the greatest flavonoid contents (28.28 ± 0.93 mg%), as well as the highest levels of major phenolic compounds including gallic acid (21.84 µg/mL), epicatechin‐gallate (6.58 µg/mL), kaempferol (6.32 µg/mL), and quercetin (8.55 µg/mL). Although further studies are required to identify the molecular mechanisms behind these anti‐angiogenic effects, 70% CE could be used as an herbal medicine, functional food ingredient, and potent angiogenesis inhibitor. Practical Application: Environmental factors such as altitude, nutrients, exposure to sunlight, and temperature can influence the type and quantity of bioactive components in plants. The advantage of cultivated plants is that the above‐mentioned factors can be artificially adjusted compared to wild plants. Based on economic efficiency, productivity, and consistent quality, anti‐angiogenesis activity of cultivated O. japonicus is of greater commercial value as a functional food than wild O. japonicus. [ABSTRACT FROM AUTHOR]

Abstract Using three correlated band approaches, namely the conventional band approach plus on-site Coulomb repulsion U , the modified Becke-Johnson functional, and hybrid functional, we have investigated inverse-Heusler ferrimagnets Cr 2 Co Z (Z =Al, Ga, In). These approaches commonly indicate that the Cr 2 CoAl synthesized recently is a precise compensated half-metal (CHM), whereas Cr 2 CoGa and Cr 2 CoIn are ferrimagnets with a small moment. This is also confirmed by the fixed spin moment approach. Analysis of the Bader charge decomposition and the radial charge densities indicates that this contrast is due to chemical differences among the Z ions. Additionally, in Cr 2 CoAl, changing the volume by ±5% or the ratio of c / a by ±2% does not alter the CHM state, suggesting that this state is robust even under application of moderate pressure or strain. Considering the observed high Curie temperature of 750 K, our results suggest that Cr 2 CoAl is a promising candidate for robust high T C CHMs. Furthermore, the electronic structure of the CHM Cr 2 CoAl is discussed. Graphical abstract Density of states in Cr 2 CoAl, indicating a compensated half-metal. Image 1 Highlights • Using correlated band theories, we showed that the inverse-Heusler Cr 2 CoAl is a precise compensated half-metal. • This state is robust under moderate strain or pressure. • The electronic structure shows interesting features, implying nontrivial topological characters. [ABSTRACT FROM AUTHOR]

The search for robust examples of the magnetic version of topological insulators, referred to as quantum anomalous Hall insulators or simply Chern insulators, so far lacks success. Our groups have explored two distinct possibilities based on multiorbital 3 d oxide honeycomb lattices. Each has a Chern insulating phase near the ground state, but materials parameters were not appropriate to produce a viable Chern insulator. Further exploration of one of these classes, by substituting open shell 3 d with 4 d and 5 d counterparts, has led to realistic prediction of Chern insulating ground states. Here we recount the design process, discussing the many energy scales that are active in participating (or resisting) the desired Chern insulator phase. [ABSTRACT FROM AUTHOR]

Acetylene (C 2 H 2 ) gas sensors were developed by synthesizing an Ag-loaded hierarchical (Hrc) ZnO nanostructure-reduced graphene oxide (Ag/ZnO Hrc-RGO) hybrid using a facile and rapid photochemical method. Morphological characterizations showed the formation of well-dispersed Ag nanoparticles-loaded hierarchical ZnO nanostructures onto the 3- to 5-layer thick RGO sheets. The hierarchical ZnO nanostructures were composed of numerous randomly oriented porous ZnO nanosheets with an average sheet thickness of 6 nm. It was also observed that Ag nanoparticles with an average diameter of 40 nm were closely affixed onto the ZnO nanosheets. Structural analysis revealed good agreement with the standard crystalline phases of ZnO, Ag and RGO. Gas-sensing characteristics of the synthesized materials were carried out in a temperature range of 25–300 °C at different C 2 H 2 gas concentrations. At 200 °C, 5 wt% Ag/ZnO Hrc-RGO hybrid showed a preferable detection of C 2 H 2 with high sensor response (12.3 toward 100 ppm), fast response time (57 s), a limit of detection (LOD) of 3 ppm, good linearity, with excellent reproducibility and selectivity. The fabricated sensor also showed less humidity effect in an open air environment. [ABSTRACT FROM AUTHOR]

The highly two-dimensional superconducting sys tem Sr(MgTi)OFeAs, recently synthesized in the range of 0.2≤ y≤0.5, shows an Mg concentration-dependent T. Reducing the Mg concentration from y=0.5 leads to a sudden increase in T, with a maximum T≈40 K at y=0.2. Using first principles calculations, the unsynthesized stoichiometric y=0 and the substoichiometric y=0.5 compounds have been investigated. For the 50 % Mg-doped phase ( y=0.5), Sr(MgTi)O layers are completely insulating spacers between FeAs layers, leading to the fermiology such as that found for other Fe pnictides. At y=0, representing a phase with metallic SrTiO layers, the Γ-centered Fe-derived Fermi surfaces (FSs) considerably shrink or disappear. Instead, three Γ-centered Ti FSs appear, and in particular two of them have similar size, like in MgB. Interestingly, FSs have very low Fermi velocity in large fractions: the lowest being 0.6×10 cm/s. Furthermore, our fixed spin moment calculations suggest the possibility of magnetic ordering, with magnetic Ti and nearly nonmagnetic Fe ions. These results indicate a crucial role of Sr(MgTi)O layers in this superconductivity. [ABSTRACT FROM AUTHOR]

The nearly well-ordered double perovskite La2CrFe06 has been synthesized recently. Contrary to previous theoretical predictions, but in agreement with experimental observations, our first principle calculations indicate an insulating ferrimagnet La2CrFe06 with antialigned S = 3/2 Cr3+ and S = 5/2 Fe3+ ions, using the local spin density approximation (LSDA), a correlated band theory LDA + U, and the Tran-Blaha modified Becke-Johnson method. Additionally, we investigated the double perovskite Sr2CrFeO6, which is as yet unsynthesized. In LSDA calculations, this system shows formally tetravalent Cr and Fe ions both having antialigned 5=1 moments, but is a simple metal. Once applying on-site Coulomb repulsion U on both Cr and Fe ions, this system becomes half metallic and the moment of Fe is substantially reduced, resulting in zero net moment. These results are consistent with our fixed spin moment studies. Our results suggest a precisely compensated half-metallic Sr2CrFeO6. [ABSTRACT FROM AUTHOR]

Background: The internet has become a major source of health information, and obtaining appropriate information requires various abilities and skills, labeled as electronic health literacy (eHealth literacy). The existing instruments for measuring eHealth literacy are outdated because they were developed during the Web 1.0 era, or not sufficiently sensitive for people with a specific condition or disease because they were designed to assess eHealth literacy over a broad range for a general population. Approximately one in ten adults worldwide live with diabetes. Health professionals have a responsibility to identify patients with low eHealth literacy to prevent them from obtaining misleading internet diabetes information. Aims: The aims were to develop a condition-specific eHealth literacy scale for diabetes and to evaluate its psychometric properties among people with type 2 diabetes. Methods: An instrument development design was used. This study recruited 453 people diagnosed with type 2 diabetes at the outpatient clinics of hospitals in 2021. Psychometric properties (internal consistency, measurement invariance, and content, structural, convergent, and known-groups validities) were analyzed. Results: An expert panel assessed content validity. Exploratory factor analysis, exploratory graph analysis, and confirmatory factor analysis (CFA) for structural validity yielded a two-factor solution (CFI = 0.977, SRMR = 0.029, RMSEA = 0.077). Cronbach's alpha and omega values were excellent for each factor (0.87–0.94). Multigroup CFA yielded configural and metric measurement invariance across the gender, age, and glycemic control status groups. Convergent validity with a comparator instrument to measure health literacy was supported by a moderate correlation, and known-groups validity determined using groups with different internet-use frequencies was satisfied with a high effect size. Conclusion: A new condition-specific eHealth literacy scale for people with type 2 diabetes was developed, comprising 10 items. The scale exhibited good psychometric properties; however, test–retest reliability must be determined for the stability of the scale and cross-cultural validity is required among different languages. The brief scale has the merits of being feasible to use in busy clinical practice and being less burdensome to respondents. The scale can be applied in clinical trials of internet-based diabetes interventions for assessing the eHealth literacy of respondents. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction‐associated steatotic liver disease (MASLD) is strongly associated with insulin resistance development. Hepatic lipid accumulation and inflammation are considered the main drivers of hepatic insulin resistance in MASLD. Cysteine‐rich 61 (Cyr61 also called CCN1), a novel secretory matricellular protein, is implicated in liver inflammation, and its role in MASLD is not clearly understood. Therefore, we investigated the role of Cyr61 in hepatic insulin resistance and lipid metabolism as major factors in MASLD pathogenesis. In high‐fat diet (HFD)‐fed C57BL/6J mice, Cyr61 was downregulated or upregulated via viral transduction. Measurements of glucose homeostasis, histological assessment of liver tissues, and gene expression and signaling pathways of lipogenesis, fatty acid oxidation, and inflammation were performed using liver samples from these mice. Cyr61 levels in HepG2 cells were reduced using RNAi‐mediated gene knockdown. Inflammation and insulin resistance were evaluated using real‐time polymerase chain reaction and western blotting. HFD/AAV‐shCyr61 mice exhibited enhanced glucose tolerance via the protein kinase B pathway, reduced hepatic inflammation, decreased lipogenesis, and increased fatty acid oxidation. Notably, HFD/AAV‐shCyr61 mice showed elevated protein expression of sirtuin 6 and phosphorylated‐AMP‐activated protein kinase. In vitro experiments demonstrated that inhibition of Cyr61 downregulated pro‐inflammatory cytokines such as interleukin‐1 beta, IL‐6, and tumor necrosis factor‐alpha via the nuclear factor kappa B/c‐Jun N‐terminal kinase pathway, and alleviated insulin resistance. Cyr61 affected hepatic inflammation, lipid metabolism, and insulin resistance. Inhibition of Cyr61 reduced inflammation, recovered insulin resistance, and altered lipid metabolism in vivo and in vitro. Therefore, Cyr61 is a potential therapeutic target in MASLD. [ABSTRACT FROM AUTHOR]

The application of an external magnetic field of sufficient strength to a spin system composed of a localized singlet can overcome the energy gap and trigger bosonic condensation and so provide an alternative method to realize exotic phases of matter in real materials. Previous research has indicated that a spin Hamiltonian with on-site Kondo coupling may be the effective many-body Hamiltonian for Ba2NiO2(AgSe)2 (BNOAS) and here we study such a Hamiltonian using a tensor network ansatz in two dimensions. Our results unveil a phase diagram which indicates the underlying phases of BNOAS. We propose, in response to the possible doping-induced superconductivity of BNOAS, a fermionic model for further investigation. We hope that our discovery can bring up further interest in both theoretical and experimental researches for related nickelate compounds. Quantum magnets are a promising platform to aid in the search for a Bose-Einstein condensate and investigations into the underlying mechanisms of these materials are an active area of research. Here, the authors present a numerical study of the two-dimensional Kondo necklace model and consider the various phases which can occur under an applied magnetic field suggesting field-induced condensate phases may exist for the quantum magnet Ba2NiO2(AgSe)2. [ABSTRACT FROM AUTHOR]

Orostachys japonicus A. Berger (O. japonicus), so-called Wa-song in Korea, a traditional food and medicine that grows on mountain rocks and roof tiles. Wa-song containing various phenolic compounds have been reported as a medicinal plant for prevention of fibrosis, cancer, inflammation, and oxidative damage. The present study was designed to examine the anti-angiogenic effects of cultivated Orostachys japonicus 70% ethanol extract (CE) in vascular endothelial growth factor (VEGF)-stimulated human umbilical vein endothelial cells (HUVECs). CE was prepared with 70% ethanol. HUVECs, rat aortic rings, and matrigel plug in mice were treated with CE (10–20 μg/mL) and VEGF (20–50 ng/mL), and the anti-angiogenic activities of CE were analyzed by SRB, wound healing, trans-well invasion, capillary-like tubule formation, rat aortas, Western blot, and matrigel plug assay. Phenolic compounds in CE were analyzed using a high-performance liquid chromatography (HPLC)-PDA system. Treatment of CE (10–20 μg/mL) markedly suppressed proliferation of HUVECs in the presence (from 136.5% to 112.2%) or absence of VEGF (from 100.0% to 92.1%). The proliferation inhibitory effect of CE was caused by G0/G1 cell cycle arrest, and the decrease of CDK-2, CDK-4, Cyclin D1 and Cyclin E1. Furthermore, CE treatment showed significant angiogenesis inhibitory effects on motility, invasion and micro-vessel formation of HUVECs, rat aortic rings and subcutaneous matrigels under VEGF-stimulation condition. In HUVECs, CE-induced anti-angiogenic effect was regulated by inhibition of the PI3K/AKT/mTOR, MAPK/p38, MAPK/ERK, FAK-Src, and VEGF-VEGFR2 signaling pathways. This study demonstrated that CE might be used as a potential natural substance, multi-targeted angiogenesis inhibitor, functional food material. Image 1 • CE blocked cell cycle progression in G0/G1 phase. • CE inhibited VEGF-induced endothelial cell migration, invasion, and differentiation into capillary-like structure in vitro. • CE inhibited phosphorylation of PI3K/AKT/mTOR and MAPK signaling pathways in HUVECs. • CE inhibited activation of VEGFR2. • CE suppressed VEGF-induced angiogenesis in vivo. [ABSTRACT FROM AUTHOR]

There are few studies on the connection between food components and circular RNA (circRNA), a type of noncoding RNA that is significant for living organisms. (−)-Epigallocatechin-3- O -gallate (EGCG) has been reported to have various biological effects, and elucidation of the molecular mechanism is important for clarifying the functionality of EGCG. In the current study, we looked at how EGCG regulates the expression of circRNA in the liver, which expresses a lot of circRNAs. Mice were given EGCG (10 mg/kg b.w.) orally for one week before circRNA microarray testing was done on their livers. The microarray analysis revealed that mice treated with EGCG had altered expression of 35 circRNAs in their livers. To clarify the function of mmu_circRNA_011775, one of the circRNAs upregulated by EGCG, mouse liver cells after the mmu_circRNA_011775 expression vector was transfected into NMuLi cells, next-generation sequencing (NGS) was used to analyze the gene expression. NGS analysis shows that the expression of the genes responsible for liver fibrosis and inflammation. Gene ontology (GO) analysis showed that mmu_circRNA_011775 changed the meaning of GO terms associated with the cardiovascular system. In the microarray, EGCG altered 35 genes expression. Among them, pre-ribosomal RNA-derived circRNA mmu_circRNA_011775 regulated the expression of various genes related to liver fibrosis and cardiovascular system. [ABSTRACT FROM AUTHOR]

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Abstract Background The prevalence of diabetes is close to reaching an epidemic level, and health literacy has recently emerged as a concept that can influence the health outcomes of patients with diabetes. Health literacy was once defined from the perspective of basic reading and understanding skills, but this has now become more comprehensive to include the abilities and skills to assess, understand, appraise, communicate, and use health information. Nevertheless, there is no instrument reflecting the comprehensive health literacy relevant to diabetes. Objectives The aims of this study were to develop a comprehensive Diabetes Health Literacy Scale and to evaluate its psychometric properties. Design An instrument-development study was applied that comprised three steps: conceptualization, item generation and content validity, and field testing of the psychometric properties. Settings A convenience sample of 462 participants was recruited from December 2016 to September of 2017 at outpatient clinics in 2 Korean university hospitals. Participants The inclusion criteria for participants were being aged at least 19 years, articulate in the Korean language, and diagnosed with diabetes, while the presence of gestational diabetes was applied as an exclusion criterion. Approximately half of the participants were female (51.1%). The participants were aged 54.5 (SD, 11.0) years, 67.1% of them were taking an oral hypoglycemic agent, and 21.9% of them had well-controlled blood-glucose levels. Methods The content validity, factorial structure validity, convergent validity, criterion validity, internal consistent reliability, and test–retest reliability of the Diabetes Health Literacy Scale were evaluated. Data were analyzed using exploratory and confirmatory factor analyses, Pearson's correlation, Cronbach's alpha, and the intraclass correlation coefficient. Results The content validity was assessed by five experts. Exploratory and confirmatory factor analyses yielded a three-factor solution. Convergent validity was demonstrated using measures of diabetes knowledge and self-efficacy. Criterion validity was demonstrated with generic health-literacy questions. Internal consistency reliability and test–retest reliability were found to be acceptable, as indicated by a Cronbach's alpha of 0.91 and an intraclass correlation coefficient of 0.89, respectively. Conclusions The Diabetes Health Literacy Scale is a new instrument that measures comprehensive aspects of informational, numeracy, and communicative health literacy. It is a short instrument, comprising only 14 items scored on a 5-point Likert scale. The instrument exhibits good psychometric properties for four validity metrics (content, structural, convergent, and criterion validity) and two reliability metrics (internal consistency and test–retest reliability). These findings indicate that the instrument can be applied in both research and clinical practice. [ABSTRACT FROM AUTHOR]

Background. Inflammation is a major cause of hepatic tissue damage and accelerates the progression of nonalcoholic fatty liver disease (NAFLD). Amphiregulin (AREG), an epidermal growth factor receptor ligand, is associated with human liver cirrhosis and hepatocellular carcinoma. We aimed to investigate the effects of AREG on hepatic inflammation during NAFLD progression, in vivo and in vitro. Methods. AREG gene expression was measured in the liver of mice fed a methionine choline-deficient (MCD) diet for 2 weeks. We evaluated inflammatory mediators and signaling pathways in HepG2 cells after stimulation with AREG. Nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were analyzed using an enzyme-linked immunosorbent assay and western blotting. Nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase, were analyzed using western blotting. Results. Proinflammatory cytokines (interleukin (IL)-6, IL-1β, and IL-8) and immune cell recruitment (as indicated by L3T4, F4/80, and ly6G mRNA expression) increased, and expression of AREG increased in the liver of mice fed the MCD diet. AREG significantly increased the expression of IL-6 and IL-1β and the production of NO, PGE2, and IL-8 in HepG2 cells. It also activated the protein expression of iNOS and COX-2. AREG-activated NF-κB and MAPKs signaling, and together with NF-κB and MAPKs inhibitors, AREG significantly reduced the protein expression of iNOS and COX-2. Conclusion. AREG plays a role in hepatic inflammation by increasing iNOS and COX-2 expression via NF-κB and MAPKs signaling. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. Materials and Methods: This was a 52‐week, multicentre, randomized, parallel‐group, open‐label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1‐2 mg/day for 12 months as an add‐on to metformin. Baseline and end of study body composition evaluations included dual‐energy X‐ray absorptiometry and abdominal computed tomography scans. Results: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: −2.59 kg BF mass, −1.94% BF%, −17.55 cm2 VAT area, −18.39 cm2 SAT area, −0.46% glycated haemoglobin, −18.25 mg/dl fasting blood glucose, −3.7 kg weight, −2.21 cm waist circumference, −1.37 kg/m2 body mass index, −6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. Conclusion: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well‐tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add‐on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: This study was to elucidate the psychometric properties of the Korean version of the Diabetes Symptom Checklist-Revised (K-DSC-R), which is a patient-reported outcome measure of diabetes symptom burden.Methods: A sample of 432 Korean patients with diabetes was recruited from university hospitals. The data were analyzed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), multitrait/multi-item correlation, Pearson's correlation, t-test, ANOVA, and Cronbach's alpha for construct, item-convergent/discriminant, concurrent, and known-groups validity, and internal consistency reliability.Results: EFA extracted a total of 29 items clustered into 7 subscales from the K-DSC-R. The construct of the seven-subscales was supported by CFA. The scaling success rates of item-convergent validity were 100% for all subscales, and those of item-discriminant validity ranged from 83.3% to 100%. Patients in more-depressed groups and in the HbA1c-uncontrolled group had higher K-DSC-R scores, satisfying the known-groups validity. The subscales of the K-DSC-R were moderately correlated with health-related quality of life, indicative of the established concurrent validity. The Cronbach's alpha of the K-DSC-R was 0.92.Conclusions: The psychometric properties of the K-DSC-R have been established. It is thus appropriate for use with respect to reliability and validity in practice and clinical trials for Korean patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction is considered a pathogenic linker in the development of non-alcoholic steatohepatitis (NASH). Inappropriate mitochondrial protein-quality control, possibly induced by insufficiency of the mitochondrial matrix caseinolytic protease P (ClpP), can potentially cause mitochondrial dysfunction. Herein, we aimed to investigate hepatic ClpP levels in a diet-induced model of NASH and determine whether supplementation of ClpP can ameliorate diet-induced NASH. NASH was induced by a high-fat/high-fructose (HF/HFr) diet in C57BL/6J mice. Stress/inflammatory signals were induced in mouse primary hepatocytes (MPHs) by treatment with palmitate/oleate (PA/OA). ClpP levels in hepatocytes were reduced using the RNAi-mediated gene knockdown technique but increased through the viral transduction of ClpP. ClpP activation was induced by administering a chemical activator of ClpP. Hepatic ClpP protein levels in C57BL/6J mice fed a HF/HFr diet were lower than the levels in those fed a normal chow diet. PA/OA treatment also decreased the ClpP protein levels in MPHs. Overexpression or activation of ClpP reversed PA/OA-induced mitochondrial dysfunction and stress/inflammatory signal activation in MPHs, whereas ClpP knockdown induced mitochondrial dysfunction and stress/inflammatory signals in these cells. On the other hand, ClpP overexpression or activation improved HF/HFr-induced NASH characteristics such as hepatic steatosis, inflammation, fibrosis, and injury in the C57BL/6J mice, whereas ClpP knockdown further augmented steatohepatitis in mice fed a HF/HFr diet. Reduced ClpP expression and subsequent mitochondrial dysfunction are key to the development of diet-induced NASH. ClpP supplementation through viral transduction or chemical activation represents a potential therapeutic strategy to prevent diet-induced NASH. Western diets, containing high fat and high fructose, often induce non-alcoholic steatohepatitis (NASH). Mitochondrial dysfunction is considered pathogenically linked to diet-induced NASH. We observed that the mitochondrial protease ClpP decreased in the livers of mice fed a western diet and supplementation of ClpP ameliorated western diet-induced NASH. [Display omitted] • Low ClpP protein levels were found in the livers of mice with non-alcoholic steatohepatitis. • ClpP deficiency induced steatohepatitis and augmented high-calorie diet-induced steatohepatitis in C57BL/6J mice. • ClpP overexpression reduced hepatic steatosis, inflammation, and fibrosis in high-calorie diet-fed C57BL/6J mice. • A chemical activator of ClpP ameliorated high-calorie diet-induced steatohepatitis in C57BL/6J mice. [ABSTRACT FROM AUTHOR]

The accumulation of hepatic lipid droplets (LDs) is a hallmark of non-alcoholic fatty liver disease (NAFLD). Appropriate degradation of hepatic LDs and oxidation of complete free fatty acids (FFAs) are important for preventing the development of NAFLD. Histone deacetylase (HDAC) is involved in the impaired lipid metabolism seen in high-fat diet (HFD)-induced obese mice. Here, we evaluated the effect of MS-275, an inhibitor of HDAC1/3, on the degradation of hepatic LDs and FFA oxidation in HFD-induced NAFLD mice. To assess the dynamic degradation of hepatic LDs and FFA oxidation in fatty livers of MS-275-treated HFD C57BL/6J mice, an intravital two-photon imaging system was used and biochemical analysis was performed. The MS-275 improved hepatic metabolic alterations in HFD-induced fatty liver by increasing the dynamic degradation of hepatic LDs and the interaction between LDs and lysozyme in the fatty liver. Numerous peri-droplet mitochondria, lipolysis, and lipophagy were observed in the MS-275-treated mouse fatty liver. Biochemical analysis revealed that the lipolysis and autophagy pathways were activated in MS-275 treated mouse liver. In addition, MS-275 reduced the de novo lipogenesis, but increased the mitochondrial oxidation and the expression levels of oxidation-related genes, such as PPARa, MCAD, CPT1b, and FGF21. Taken together, these results suggest that MS-275 stimulates the degradation of hepatic LDs and mitochondrial free fatty acid oxidation, thus protecting against HFD-induced NAFLD. [ABSTRACT FROM AUTHOR]

Objective: The natural course of diabetes of the exocrine pancreas (DEP) is not well established. We aimed to compare the risk of insulin initiation, diabetic complications, and mortality between DEP and type 2 diabetes.Research Design and Methods: Using the Korean National Health Insurance Service-Health Screening Cohort between 2012 and 2017, we divided patients with diabetes into those with diabetes without prior pancreatic disease (indicated type 2 diabetes, n = 153,894) and diabetes with a prior diagnosis of pancreatic disease (indicated DEP, n = 3,629). ICD-10 codes and pharmacy prescription information were used to define type 2 diabetes, DEP, and acute and chronic diabetes complications. Kaplan-Meier curves were produced to compare insulin use over time between groups. We created logistic regression models for odds of progression to diabetic complications and mortality.Results: DEP was associated with a higher risk of insulin use than type 2 diabetes (adjusted hazard ratio 1.38 at 5 years [95% CI 1.30-1.47], P < 0.0001). Individuals with DEP showed higher risks of hypoglycemia (odds ratio 1.85 [1.54-2.21], P < 0.0001), diabetic neuropathy (1.38 [1.28-1.49], P < 0.0001), nephropathy (1.38 [1.27-1.50], P < 0.0001), retinopathy (1.10 [1.01-1.20], P = 0.0347), coronary heart disease (1.59 [1.48-1.70], P < 0.0001), cerebrovascular disease (1.38 [1.28-1.49], P < 0.0001), and peripheral arterial disease (1.34 [1.25-1.44], P < 0.0001). All-cause mortality was higher in those with DEP (1.74 [1.57-1.93], P < 0.0001) than in those with type 2 diabetes.Conclusions: DEP is more likely to require insulin therapy than type 2 diabetes. Hypoglycemia, micro- and macrovascular complications, and all-cause mortality events are higher in DEP compared with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Current advances in technology have enabled the development of a computer-based questionnaire that provides advantages over the paper-based mode of administration, such as automatic data entry, storage and calculations. However, before implementing a computer-based questionnaire, its equivalence with the original paper-based questionnaire must first be demonstrated. The purpose of this study was to evaluate the measurement equivalence of the computerized Diabetes- Specific Quality-of- Life questionnaire ( cD- QOL) with its original paper-based counterpart. A two-period crossover design was used in this study. The measurement equivalence was evaluated using quadratic weighted kappa coefficients, intraclass correlations and Cronbach's alpha comparisons. The cD- QOL was equivalent to its original paper-based counterpart. Participants preferred the cD- QOL over the paper-based questionnaire and reported that it was easy to use. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The aims of this study were to develop a diabetes-specific quality-of-life (D-QOL) scale and to determine its psychometric properties. Methods: An initial pool of items was generated based on a conceptual construct and attributes of health-related quality of life. The items were reviewed by experts, and a pilot test was conducted. A content-validated preliminary D-QOL scale was verified for use with psychometric tests on 402 patients who were recruited from 3 hospitals in Korea. The data were analyzed using exploratory and confirmatory factor analyses, Cronbach''s alpha, generalizability coefficients, ANOVA, and Pearson''s correlations. Results: From exploratory analyses, a total of sixteen items clustered four factors were extracted. The four-factor structure was supported by confirmatory factor analysis. Concurrent validity was established with the 36-item Short-Form Health Survey. As hypothesized, the D-QOL scores were worse in severely or moderately depressed patients than in those who were either less depressed or not depressed, implying satisfactory known-groups validity. The reliability of the D-QOL scale was supported by Cronbach''s alpha and generalizability coefficients. Conclusions: The D-QOL scale is a simple and brief scale, the use of which is feasible in practice. It demonstrated excellent psychometric properties, and so may also be used in clinical research. [Copyright &y& Elsevier]

Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of liver diseases characterized by steatosis, inflammation, and fibrosis. This study aimed to investigate the potential of dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors in alleviating the progression of NAFLD. The NAFLD model was generated by feeding male C57BL/6J mice a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) for 7 weeks. After 2 weeks of CDAHFD feeding, the NAFLD model mice were assigned to four groups, namely (ⅰ) VEHICLE, (ⅱ) gemigliptin (GEMI), (ⅲ) empagliflozin (EMPA), and (ⅳ) GEMI + EMPA. For the next 5 weeks, mice received the vehicle or the drug based upon the group to which they belonged. Thereafter, the triglyceride concentration, extent of fibrosis, and the expression of genes encoding inflammatory cytokines, chemokines, and antioxidant enzymes were analyzed in the livers of mice. The NAFLD activity score and hepatic fibrosis grade were assessed via hematoxylin and eosin and Sirius Red staining of the liver tissue samples. All mice belonging to the GEMI, EMPA, and GEMI + EMPA groups showed improvements in the accumulation of liver triglycerides and the expression of inflammatory cytokines and chemokines. Additionally, the oxidative stress was reduced due to inhibition of the c-Jun N-terminal kinase pathway and upregulation of the antioxidant enzymes. Furthermore, in these three groups, the galectin-3 and interleukin 33-induced activity of tumor necrosis factor-α was inhibited, thereby preventing the progression of liver fibrosis. These findings suggest that the GEMI, EMPA, and GEMI + EMPA treatments ameliorate hepatic steatosis, inflammation, oxidative stress, and fibrosis in CDAHFD-induced NAFLD mouse models. • Gemigliptin and empagliflozin reduce hepatic steatosis. • Gemigliptin and empagliflozin reduce inflammatory cytokine expression. • Gemigliptin and empagliflozin enhance hepatic anti-oxidant enzyme expression. • Gemigliptin and empagliflozin reduce fibrosis by decreasing galectin-3 and IL-33. • Gemigliptin and empagliflozin alleviate the progression of NAFLD. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the efficacy and safety of switching to teneligliptin from other dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM) inadequately controlled despite treatment with a stable dose of other DPP-4 inhibitors. Methods: Patients with glycosylated hemoglobin (HbA1c) ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other antidiabetic agents, for at least 3 months were enrolled in this study. Patients on DPP-4 inhibitors administered prior to participation in this study were switched to 20 mg teneligliptin once daily and the dose was maintained for the 52-week study period. The primary endpoint was the change in HbA1c at week 12. Fasting plasma glucose (FPG) and the blood lipid profile were also evaluated. Adverse events were monitored for safety assessment. Results: At weeks 12, 24, and 52, the HbA1c values significantly decreased by − 0.39, − 0.44, and − 0.52%, respectively, compared to the baseline value (p < 0.0001); in addition, 56.3, 60.3, and 62.3% of patients, respectively, achieved decreases in HbA1c of at least 0.3%, and 40.1, 46.5, and 52.4% of patients, respectively, achieved decreases in HbA1c of at least 0.5%. The proportion of the patient population achieving HbA1c < 7.0% increased throughout the study period, reaching 30.4, 35.4, and 36.9% at weeks 12, 24, and 52, respectively; at these same time points, the percentage of patients achieving HbA1c < 6.5% increased to 9.5, 11.9, and 13.2% of the total study population. FPG levels and lipid parameters were also significantly decreased after teneligliptin treatment. There were no significant safety concerns. Conclusion: Our results suggest the significant glucose-lowering effect of teneligliptin after switching from other DPP-4 inhibitors in patients with T2DM. The improvement in glycemic control was maintained for up to 52 weeks without safety concerns. [ABSTRACT FROM AUTHOR]

Background and Aim: Non‐alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to non‐alcoholic steatohepatitis, which is characterized by hepatic inflammation that can progress to fibrosis, cirrhosis, and hepatocellular carcinoma. Visfatin, an adipocytokine, was reported to induce pro‐inflammatory cytokines and can be associated with liver fibrosis. We investigated the role of visfatin on hepatic inflammation and fibrosis in a methionine‐choline‐deficient (MCD)‐diet‐induced steatohepatitis mouse model. Methods: Eight‐week‐old male C57BL/6 J mice were randomly assigned into one of three groups: (1) saline‐injected control diet group; (2) saline‐injected MCD diet group; and (3) visfatin‐injected MCD diet group (n = 8 per group). Mice were administered intravenous saline or 10 μg/kg of recombinant murine visfatin for 2 weeks. Histologic assessment of liver and biochemical and molecular measurements of endoplasmic reticulum (ER) stress, reactive oxidative stress (ROS), inflammation, and fibrosis were performed in livers from these animals. Results: Visfatin injection aggravated hepatic steatosis and increased plasma alanine aminotransferase and aspartate aminotransferase concentrations. Visfatin increased inflammatory cell infiltration (as indicated by F4/80, CD68, ly6G, and CD3 mRNA expression) and expression of chemokines in the liver. Visfatin also increased the expression of pro‐inflammatory cytokines (IL‐1β, TNF‐α, and IL‐6) and activated fibrosis markers (CTGF, TIMP1, collagen 1α2, collagen 3α2, αSMA, fibronectin, and vimentin) in liver. Livers of visfatin‐injected mice showed upregulation of ER stress and ROS and activation of JNK signaling. Conclusions: These results suggest that visfatin aggravates hepatic inflammation together with induction of ER and oxidative stress and exacerbates fibrosis in an MCD‐diet‐fed mouse model of NAFLD. [ABSTRACT FROM AUTHOR]

Background. Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and gemigliptin therapy. Methods. RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, gemigliptin, or empagliflozin plus gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation. Results. LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, gemigliptin, and empagliflozin plus gemigliptin, respectively. Empagliflozin and gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling. Conclusions. Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter 2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs whose anti-inflammatory properties have recently become useful in tackling metabolic syndromes in chronic inflammatory diseases, including diabetes and obesity. We investigated whether empagliflozin (SGLT2 inhibitor) and gemigliptin (DPP-4 inhibitor) improve inflammatory responses in macrophages, identified signalling pathways responsible for these effects, and studied whether the effects can be augmented with dual empagliflozin and gemigliptin therapy.Methods: RAW 264.7 macrophages were first stimulated with lipopolysaccharide (LPS), then cotreated with empagliflozin, gemigliptin, or empagliflozin plus gemigliptin. We conducted quantitative RT-PCR (qRT-PCR) to determine the most effective anti-inflammatory doses without cytotoxicity. We performed ELISA and qRT-PCR for inflammatory cytokines and chemokines and flow cytometry for CD80, the M1 macrophage surface marker, to evaluate the anti-inflammatory effects of empagliflozin and gemigliptin. NF-κB, MAPK, and JAK2/STAT signalling pathways were examined via Western blotting to elucidate the molecular mechanisms of anti-inflammation.Results: LPS-stimulated CD80+ M1 macrophages were suppressed by coincubation with empagliflozin, gemigliptin, and empagliflozin plus gemigliptin, respectively. Empagliflozin and gemigliptin (individually and combined) inhibited prostaglandin E2 (PGE2) release and COX-2, iNOS gene expression in LPS-stimulated RAW 264.7 macrophages. These three treatments also attenuated the secretion and mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IFN-γ, and proinflammatory chemokines, such as CCL3, CCL4, CCL5, and CXCL10. All of them blocked NF-κB, JNK, and STAT1/3 phosphorylation through IKKα/β, MKK4/7, and JAK2 signalling.Conclusions: Our study demonstrated the anti-inflammatory effects of empagliflozin and gemigliptin via IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 pathway downregulation in macrophages. In all cases, combined empagliflozin and gemigliptin treatment showed greater anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Background/Aims. This study was designed to identify the clinical characteristics of Korean patients with type 2 diabetes according to metformin use. Methods. This cross-sectional study based on the Korean National Diabetes Program 2 registry used its baseline clinical data collected from seven participating university hospitals in Korea. Patients with no significant changes in their oral hypoglycemic agents and no diabetes-related complications within the year prior to participation were enrolled. Patients' clinical characteristics according to metformin use were analyzed. Results. Among 858 subjects included in the analyses, 706 were metformin users and 152 were nonmetformin users. Metformin users were significantly younger and had higher and glycated hemoglobin with significantly lower rates of accompanying microvascular complications such as retinopathy, cataracts, overt proteinuria, renal insufficiency, and peripheral neuropathy than nonusers. Meanwhile, there was a significantly lower prevalence of malignancy and depression among metformin users. These associations remained significant in multivariate analyses. The prevalence rate of macrovascular complications was not significantly different between the two groups. Conclusions. There were significant differences with respect to clinical characteristics and comorbidity prevalence according to metformin use among Korean type 2 diabetes patients. Long-term follow-up of these patients is necessary to observe how this difference will affect clinical outcomes for these patients. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is excessive fat build-up in the liver without alcohol consumption and includes hepatic inflammation and damage. Excessive influx of fatty acids to liver from circulation is thought to be a pathogenic cause for the development of NAFLD. Thus, inhibition of fatty acid intake into hepatocyte would be a maneuver for protection from high fat diet (HFD)-induced NAFLD. This study was initiated to determine whether sodium fluorocitrate (SFC) as a fatty acid uptake inhibitor could prevent palmitate-induced lipotoxicity in hepatocytes and protect the mice from HFD-induced NAFLD. SFC significantly inhibited the cellular uptake of palmitate in HepG2 hepatocytes, and thus prevented palmitate-induced fat accumulation and death in these cells. Single treatment with SFC reduced fasting-induced hepatic steatosis in C57BL/6J mice. Concurrent treatment with SFC for 15 weeks in HFD-fed C57BL/6J mice prevented HFD-induced fat accumulation and stress/inflammatory signal activation in the liver. SFC restored HFD-induced increased levels of serum alanine aminotransferase and aspartate aminotransferases as hepatic injury markers in these mice. SFC treatment also improved HFD-induced hepatic insulin resistance, and thus ameliorated HFD-induced hyperglycemia. In conclusion, inhibition of fatty acid mobilization into liver through SFC treatment can be a strategy to protect from HFD-induced NAFLD. [ABSTRACT FROM AUTHOR]

Introduction: Teneligliptin, an antidiabetic agent classified as a class III dipeptidyl peptidase-4 (DPP-4) inhibitor, has a unique structural feature that provides strong binding to DPP-4 enzymes. We investigated the efficacy and safety of switching patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control on a stable dose of other DPP-4 inhibitors to teneligliptin. Methods: Patients with T2DM whose glycosylated hemoglobin (HbA1c) levels were ≥ 7% despite taking DPP-4 inhibitors other than teneligliptin, with or without other hypoglycemic agents, for at least 3 months were enrolled. The DPP-4 inhibitors taken before participating in the study were switched to 20 mg qd teneligliptin, and this was to be maintained for 52 weeks. The primary end point was the change in HbA1c levels after 12 weeks. Metabolic parameters including fasting plasma glucose (FPG) and blood lipids were assessed also. To assess safety, adverse and hypoglycemic events were monitored. The data from baseline to week 12 were used for analysis in this interim report. Results: The mean change in HbA1c levels from baseline to week 12 was − 0.44%. At week 12, the percentage of patients achieving HbA1c < 7.0% was 31.6% and that of achieving HbA1c < 6.5% was 11.4%, respectively. In 41.2% of patients, the HbA1c levels decreased by at least 0.5% at 12 weeks. The mean change in FPG levels from baseline to week 12 was − 11.5 mg/dl. No severe hypoglycemia was reported. Conclusion: After switching to teneligliptin, HbA1c levels decreased significantly in patients with T2DM inadequately controlled with other DPP-4 inhibitors. Trial Registration: ClinicalTrials.gov, NCT03793023. Funding: Handok Inc. [ABSTRACT FROM AUTHOR]

Background. It has been suggested that visfatin, which is an adipocytokine, exhibits proinflammatory properties and is associated with insulin resistance. Insulin resistance and inflammation are the principal pathogeneses of nonalcoholic fatty liver disease (NAFLD), but the relationship, if any, between visfatin and NAFLD remains unclear. Here, we evaluated the effects of visfatin on hepatic inflammation and insulin resistance in HepG2 cells and examined the molecular mechanisms involved. Methods. After treatment with visfatin, the inflammatory cytokines IL-6, TNF-α, and IL-1β were assessed by real-time polymerase chain reaction (RT-PCR) and immunocytochemical staining in HepG2 cells. To investigate the effects of visfatin on insulin resistance, we evaluated insulin-signaling pathways, such as IR, IRS-1, GSK, and AKT using immunoblotting. We assessed the intracellular signaling molecules including STAT3, NF-κB, IKK, p38, JNK, and ERK by western blotting. We treated HepG2 cells with both visfatin and either AG490 (a JAK2 inhibitor) or Bay 7082 (an NF-κB inhibitor); we examined proinflammatory cytokine mRNA levels using RT-PCR and insulin signaling using western blotting. Results. In HepG2 cells, visfatin significantly increased the levels of proinflammatory cytokines, reduced the levels of proteins (e.g., phospho-IR, phospho-IRS-1 (Tyr612), phospho-AKT, and phospho-GSK-3α/β) involved in insulin signaling, and increased IRS-1 S307 phosphorylation compared to controls. Interestingly, visfatin increased the activities of the JAK2/STAT3 and IKK/NF-κB signaling pathways but not those of the JNK, p38, and ERK pathways. Visfatin-induced inflammation and insulin resistance were regulated by JAK2/STAT3 and IKK/NF-κB signaling; together with AG490 or Bay 7082, visfatin significantly reduced mRNA levels of IL-6, TNF-α and IL-1β and rescued insulin signaling. Conclusion. Visfatin induced proinflammatory cytokine production and inhibited insulin signaling via the STAT3 and NF-κB pathways in HepG2 cells. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of ipragliflozin vs placebo as add‐on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). Methods: This double‐blind, placebo‐controlled, multi‐centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). Results: In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add‐on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were −0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference −0.83% [95% CI −1.07 to −0.59]; P < .0001). More ipragliflozin‐treated patients than placebo‐treated patients achieved HbA1c target levels of <7.0% (44.4% vs 12.1%) and < 6.5% (12.5% vs 1.5%) at EOT (P < .05 for both). Fasting plasma glucose, fasting serum insulin, body weight and homeostatic model assessment of insulin resistance decreased significantly at EOT, in favour of ipragliflozin (adjusted mean difference −1.64 mmol/L, −1.50 μU/mL, −1.72 kg, and −0.99, respectively; P < .05 for all). Adverse event rates were similar between groups (ipragliflozin: 51.4%; placebo: 50.0%). No previously unreported safety concerns were noted. Conclusions: Ipragliflozin as add‐on to metformin and sitagliptin significantly improved glycaemic variables and demonstrated a good safety profile in Korean patients with inadequately controlled T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: We investigated the failure of monotherapy in patients with type 2 diabetes mellitus in real practice settings. Materials and Methods: The Korean National Diabetes Program was a prospective, multicenter observational cohort study of type 2 diabetes mellitus patients in Korea. Of the 3,950 patients enrolled in the study, we studied 998 who were continuously maintained on monotherapy for at least 90 days at six participating centers. To balance the baseline characteristics of patients in each group, we used propensity matching at a 1:1 ratio (metformin vs sulfonylureas) and 4:1 ratio (metformin vs meglitinides and metformin vs alpha‐glucosidase inhibitors [aGIs]). The hazard ratios (HRs) of treatments (compared with metformin) were determined by Cox's proportional hazards regression modeling. Results: The median follow‐up time was 56 months, and monotherapy failed in 45% of all patients. The annual incidences of failure were 15.6%, 21.3%, 27% and 9.6% in the metformin, sulfonylurea, meglitinide and aGI groups. Compared with metformin, sulfonylureas and meglitinides were associated with higher risks of monotherapy failure (HR 1.39, 95% confidence interval [CI] 1.08–1.80; HR 1.92, 95% CI 1.13–3.27), and aGIs with risks similar to that of metformin (HR 0.80, 95% CI 0.44–1.45). When analyzed by failure type, sulfonylureas, meglitinides and aGIs were associated with a higher risk of a switch to other agents (HR 4.43, 95% CI 2.14–9.17; HR 18.80, 95% CI 6.21–56.93; HR 4.25, 95% CI 1.49–12.13), and aGIs with a lower risk of prescription of add‐on second agents (HR 0.16, 95% CI 0.04–0.64). Conclusions: Metformin was associated with a lower failure risk than were sulfonylureas and meglitinides, but a comparable aGI failure rate. [ABSTRACT FROM AUTHOR]

Aims: To estimate the risk of diabetic ketoacidosis (DKA) associated with sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor treatment compared with the risk associated with dipeptidyl‐peptidase‐4 (DPP‐4) inhibitor treatment. Methods: A nationwide population‐based cohort study using claims data from the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed. A total of 56 325 patients who were started on SGLT2 inhibitors were included in this study and were matched with same number of patients who were started on DPP‐4 inhibitors using propensity score matching. Kaplan–Meier curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for DKA. Results: The risk of hospitalization for DKA was not increased in SGLT2 inhibitor users vs DPP‐4 inhibitor users (hazard ratio [HR] 0.956, 95% confidence interval [CI] 0.581‐1.572; P = .996). The incidence rate of hospitalization for DKA during the first 30 days after initiation of the SGLT2 inhibitor was 2.501 cases per 1000 person‐years, which was higher than the rate during 3 years (0.614 cases per 1000 person‐years). SGLT2 inhibitor use was associated with a higher HR in patients with diabetic microvascular complications (HR 2.044, 95% CI 0.900‐4.640; P = .088) and in patients taking diuretics (HR 3.648, 95% CI 0.720‐18.480; P = .118), although these associations were not statistically significant. Conclusion: We found that SGLT2 inhibitor treatment did not increase the risk of DKA compared with DPP‐4 inhibitor treatment. Our findings suggest that patients prescribed diuretics or those with microvascular complications may have a greater tendency to be hospitalized for DKA. [ABSTRACT FROM AUTHOR]

Aim: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long‐term glycaemic control and the preservation of β‐cell function in people with type 2 diabetes mellitus (T2DM). Methods: Newly diagnosed drug‐naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow‐up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti‐glutamic acid decarboxylase autoantibody‐positive. Results: Both intensive treatment methods were effective for short‐term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow‐up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well‐controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow‐up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug‐free glycaemic remission compared with the COAD method (P = .015). Conclusions: The findings indicate that outpatient clinic‐based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in β‐cell function and glycaemic control over the long term, without serious adverse events. [ABSTRACT FROM AUTHOR]

Background. Information on the risk of acute pancreatitis in patients receiving dipeptidyl-peptidase IV inhibitors (DPP-4i) is limited and controversial. One study suggested that the differences in findings between these meta-analyses were attributed to whether they included large randomized control trials with cardiovascular outcomes or not. The aim of our study was to determine whether the use of DPP-4i increases the risk of acute pancreatitis compared with sulfonylurea (SU) and whether the risk is higher in patients with underlying cardiovascular disease (CVD). Methods. A population-based cohort study was performed using Korean National Health Insurance Service-National Sample Cohort data. We included 33,395 new users of SU and DPP-4i from 1 January 2008 to 31 December 2015. SU-treated patients and DPP-4i-treated patients were matched by 1 : 1 propensity score matching. We used Kaplan–Meier curves and Cox proportional hazards regression analysis to calculate the risk of acute pancreatitis. Results. The hazard ratio (HR) of hospitalization for acute pancreatitis was 0.642 (95% confidence interval (CI): 0.535–0.771) in DPP-4i-treated patients compared with SU-treated patients. The HR of DPP-4i use was also lower than that of SU use in patients without underlying CVD (HR: 0.591; 95% CI: 0.476–0.735) but not in patients with underlying CVD (HR: 0.727; 95% CI: 0.527–1.003). Conclusion. Our findings suggest that DPP-4i is less likely to cause drug-induced pancreatitis than SU. This finding was not evident in patients with CVD, but DPP-4i was not more likely to induce pancreatitis in these patients than SU was. [ABSTRACT FROM AUTHOR]

Aim: Diabetes mellitus (DM) patients are susceptible to foot injury or foot diseases such as diabetic foot and peripheral arterial disease. Although these conditions are considered important, few studies have investigated them in detail. Therefore, we investigated the epidemiology of diabetic foot complications (DFC) with respect to the effects on the public healthcare system.Methods: We evaluated the incidence, clinical characteristics, health service utilization frequency and medical expenses of DFC in type 2 DM patients in the Korea National Diabetes Program (KNDP), the largest multi-center, prospective cohort in Korea (n=4405). To determine precise outcomes, we used national representative databases, including claims data from the Health Insurance Review & Assessment Service of Korea.Results: During a median follow-up period of 3.30years, 528 patients (12.0%) were newly diagnosed with DFC at an incidence rate of 43.02 cases per 1000 person-years. The patients with DFC were significantly older than patients without DFC, but other clinical characteristics were similar between the two groups. The patients with DFC had more hospital visits (p<0.001), longer duration of hospitalization (p<0.001), and increased expenses (p<0.001) compared to patients without DFC. After multiple adjustments, the differences in number of hospital visits and medical expenses were consistent. In a before and after comparison within the DFC group, all three variables increased significantly after the onset of DFC (p<0.001).Conclusions: DFC were significantly associated with poor clinical outcomes and caused a substantial burden to the national healthcare system in Korea. Therefore, intervention to prevent DFC is important. [ABSTRACT FROM AUTHOR]

Background Gemigliptin is a new dipeptidyl peptidase- IV inhibitor. We investigated the efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes ( T2D). Methods A total of 433 T2D patients with a glycosylated haemoglobin ( HbA1c) level of 7.5% to 11.0% and a fasting plasma glucose ( FPG) concentration <270 mg/dL were randomly assigned to 3 groups: (1) gemigliptin 50 mg qd + metformin 1000 to 2000 mg qd (titrated individually), (2) gemigliptin 50 mg qd, or (3) metformin 1000 to 2000 mg qd. The primary end-point was the change in HbA1c level after 24 weeks. Secondary end-points were the changes in FPG, insulin, proinsulin and C-peptide levels. The percentages of responders who achieved an HbA1c level <7% (or <6.5%) were compared between treatment groups. Results Baseline HbA1c levels were 8.7% in all groups. The mean changes in HbA1c level from baseline to week 24 were −2.06%, −1.24% and −1.47% in the combination, gemigliptin monotherapy and metformin monotherapy groups, respectively. The 95% confidence intervals for between-group differences in HbA1c changes were −1.02 to −0.63 in the combination group vs the gemigliptin group and −0.82 to −0.41 vs the metformin group, which confirmed the superiority of combination therapy. A significantly higher percentage of patients in the combination therapy group reached the target HbA1c level <7% (or <6.5%) compared with the monotherapy groups. No severe side effects were observed. Conclusions In T2D patients, the initial combination of gemigliptin and metformin had superior efficacy without safety concerns compared with monotherapy with either drug. [ABSTRACT FROM AUTHOR]

Aim: Because the incidence of type 2 diabetes in Korea has not been clearly defined, we examined the incidence of this condition and its association with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other risk factors in a 12-year follow-up Korean community-based prospective cohort study.Methods: We recruited 7542 subjects aged 40-69years without diabetes at baseline examination from the Korean Genome and Epidemiology Study and followed these subjects for 12years biennially. Diabetes was defined according to the 2010 American Diabetes Association criteria. The incidence of type 2 diabetes and the predictors of progression to diabetes were analyzed according to baseline glucose tolerance.Results: The overall incidence of type 2 diabetes was 22.1 per 1000person-years. Subjects with combined IFG-IGT at baseline had the highest incidence of diabetes, which was more than two-fold that of individuals with isolated IFG or isolated IGT (114.4 vs. 51.3 vs. 53.1 per 1000person-years). A multivariate Cox proportional hazards model analysis showed that combined IFG-IGT, which were strong predictors of diabetes, as well as age, urban residence, family history of diabetes, smoking status, abdominal obesity, hypertension, high triglycerides and low HDL cholesterols were also independently associated with progression to diabetes.Conclusions: The incidence of type 2 diabetes is relatively high in our Korean community-based sample. Combined IFG-IGT are strong predictors of type 2 diabetes. Measurement of 2-hour plasma glucose in addition to fasting plasma glucose is necessary for the detection of individuals at high risk for development of diabetes. [ABSTRACT FROM AUTHOR]

Aims. Dipeptidyl-peptidase IV inhibitors (DPP-4i) are among the most popular oral antidiabetic agents. However, the effects of DPP-4i on diabetic nephropathy are not well-established. The aim of this study was to determine the renoprotective effects of DPP-4i, using albuminuria and glomerular filtration rate (GFR) as indicators, in type 2 diabetes mellitus (T2DM) patients. Methods. This retrospective observational cohort study used the clinical database of a tertiary hospital. The changes of urine albumin/creatinine ratio (UACR), estimated GFR (eGFR), and metabolic parameters after treatment were compared with the changes of those parameters before treatment using paired Student’s t-test. Results. The mean UACR in the entire study population decreased to approximately 45 mg/g 1 year after DPP-4i treatment, while it was increased approximately 39 mg/g 1 year before DPP-4i treatment (p<0.05). Patients with macroalbuminuria showed a significant reduction in albumin levels after DPP-4i treatment (p<0.05); however, patients with microalbuminuria and normoalbuminuria did not show improvements in albuminuria levels after treatment. Although eGFR was not changed 1 year after DPP-4i treatment, reductions in eGFR were slowed in patients with microalbuminuria and reversed in the macroalbuminuria or normoalbuminuria groups, 4 years after treatment. Conclusions. Administration of DPP-4i reduces urine albumin excretion and mitigates reduction of eGFR in T2DM patients. [ABSTRACT FROM AUTHOR]

Aim: Although hypoglycemia is associated with cognitive dysfunction, including dementia, in patients with type 2 diabetes mellitus (DM), the data are equivocal. The purpose of this study was to investigate the association between hypoglycemia, dementia, and other cognitive dysfunctions.Methods: This was a prospective observational study based upon the Korea National Diabetes Program (KNDP). Among the 4540 participants in the KNDP cohort, individuals aged ⩾60years without any history of hypoglycemia or cognitive dysfunction (n=1957) were included. Nationally representative data from the Health Insurance Review and Assessment Service of Korea claim database were used to obtain a more precise determination of patient outcome.Results: During a mean follow-up period of 3.4±0.9years, 118 subjects experienced hypoglycemia-related events. The incidence of dementia and cognitive dysfunction was 7.5 cases per 1000 person-years (PY) and 0.61 cases per 1000 PY, respectively. In the subjects who experienced hypoglycemic events (relative to those who did not), the incidence of dementia was significantly higher (P=0.0139), but the incidence of cognitive dysfunction was not (P=0.1106). Hypoglycemic events were associated with dementia (HR, 2.689; 95% CI, 1.080-6.694, P=0.0335) following multiple adjustments. There was also a significant linear trend toward an increased dementia risk commensurate with an increasing number of hypoglycemic events (P=0.0286).Conclusions: Hypoglycemia is significantly associated with the risk of dementia in Korean type 2 DM patients aged ⩾60years. [ABSTRACT FROM AUTHOR]

Background The aim of the present 24-week multicentre randomized non-inferiority trial was to compare the efficacy and safety of two insulin intensification strategies in uncontrolled type 2 diabetes despite optimized basal insulin therapy. Methods Patients with fasting plasma glucose ( FPG) <130 mg/dL and HbA1c 7.0%-10.0% while on insulin glargine were randomized to a basal-prandial group (stepwise addition of insulin glulisine) or a premixed insulin group (insulin aspart/insulin aspart protamine 30/70 starting with 6 IU twice daily). The primary endpoint was the change in HbA1c after 24 weeks (non-inferiority margin 0.4%). Results At Week 24, the adjusted mean change from baseline HbA1c was -0.94 ± 0.09% and -1.04 ± 0.09% in basal-prandial and premixed insulin groups, respectively, with a mean difference of -0.09% (95% confidence interval [ CI] -0.35, 0.16). A lower rate of hypoglycemia with a similar reduction in HbA1c was observed during stabilization of the total daily insulin dose in the premixed insulin group (Weeks 0-12). After stabilization of the total daily insulin dose, the rate of hypoglycemia and the total daily insulin dose were similar in the two groups. Conclusions The efficacy and safety of the two intensifying regimens were similar after stabilization of the total daily insulin dose when oral agents were maintained. Starting with a lower total daily insulin dose with a gradual change in the treatment regimen was helpful in reducing the rate of hypoglycemia during initial stabilization of the total daily insulin dose. [ABSTRACT FROM AUTHOR]

Background and Aims: Hypoglycemia is one of the most important adverse events in individuals with type 2 diabetes mellitus (T2DM). However, hypoglycemia-related events are usually overlooked and have been documented less in clinical practice. Materials and Methods: We evaluated the incidence, clinical characteristics, and medical expenses of hypoglycemia related events in T2DM patients based on the Korea National Diabetes Program (KNDP), which is the largest multi-center, prospective cohort in Korea (n = 4,350). For accurate outcomes, the KNDP data were merged with claims data from the Health Insurance Review and Assessment Service (HIRA) of Korea. Results: During a median follow-up period of 3.23 years (95% CI: 3.14, 3.19), 88 subjects (2.02%) were newly diagnosed with hypoglycemia, and the incidence of hypoglycemia was 6.44 cases per 1,000 person-years (PY). Individuals with hypoglycemia were significantly older (59.7±10.7 vs. 53.3±10.4 years, p < 0.001), had more hospital visits (121.94±126.88 days/PY, p < 0.001), had a longer hospital stays (16.13±29.21 days/PY, p < 0.001), and incurred greater medical costs ($2,447.56±4,056.38 vs. $1,336.37±3,403.39 /PY, p < 0.001) than subjects without hypoglycemia. Conclusion: Hypoglycemia-related events were infrequently identified among the medical records of T2DM subjects. However, they were associated significantly with poor clinical outcomes, and thus, hypoglycemia could have a substantial burden on the Korean national healthcare system. [ABSTRACT FROM AUTHOR]

Introduction: The relationship between a perioperative change in sarcopenic status and clinical outcome of liver transplantation (LT) is unknown. We investigated whether post-LT sarcopenia and changes in sarcopenic status were associated with the survival of patients. Method: This retrospective study was based on a cohort of 145 patients from a single transplant center who during a mean of 1 year after LT underwent computed tomography imaging evaluation. The cross-sectional area of the psoas muscle of LT patients was compared with that of age- and sex-matched healthy individuals. The Cox proportional hazards regression model was used to determine whether post-LT sarcopenia and changes in sarcopenic status affect post-LT survival. Results: The mean age at LT of the 116 male and 29 female patients was 50.2 ± 7.9 years; the mean follow-up duration was 51.6 ± 32.9 months. All pre-LT patients with sarcopenia still had sarcopenia 1 year after LT; 14 (15%) patients had newly developed sarcopenia. The mean survival duration was 91.8 ± 4.2 months for non-sarcopenic patients and 80.0 ± 5.2 months for sarcopenic patients (log-rank test, p = 0.069). In subgroup analysis, newly developed sarcopenia was an independent negative predictor for post-LT survival (hazard ratio: 10.53, 95% confidence interval: 1.37–80.93, p = 0.024). Conclusion: Sarcopenia in LT recipients did not improve in any of the previously sarcopenic patients and newly developed within 1 year in others. Newly developed sarcopenia was associated with increased mortality. Newly developed sarcopenia can be used to stratify patients with regard to the risk of post-LT mortality. [ABSTRACT FROM AUTHOR]

High levels of plasma free fatty acid are thought to contribute to the loss of pancreatic beta-cells in type 2 diabetes. In particular, saturated fatty acid such as palmitate or stearate can induce apoptosis in cultured beta cells (lipotoxicity). Endoplasmic reticulum stress is a critical mediator of free fatty acid-induced lipotoxicity. Recently, disorders in mitochondrial respiratory metabolism have been linked to lipotoxicity. Since iron is a critical component of respiratory metabolism, this study is initiated to determine whether abnormal iron metabolism is involved in palmitate-induced beta cell death. Immunoblotting analysis showed that treatment of INS-1 beta cells with palmitate reduced the level of transferrin receptor 1 (TfR1), but increased the level of heavy chain ferritin (FTH). In addition, palmitate reduced intracellular labile iron pool. Whereas iron depletion through treatment with iron-chelators deferoxamine or deferasirox augmented palmitate-induced cell death, iron supplementation with ferric chloride, ferrous sulfate, or holo-transferrin significantly protected cells against palmitate-induced death. Furthermore, overexpression of TfR1 reduced palmitate-induced cell death, whereas knockdown of TfR1 augmented cell death. In particular, treatment with deferoxamine increased the level of endoplasmic reticulum (ER) stress markers phospho-PERK, phospho-eIF2α, CHOP and phospho-c-Jun N-terminal kinase. Treatment with chemical chaperone significantly protected cells against deferoxamine-induced apoptosis. Iron supplementation also protected cells against palmitate-induced primary islet death. These data suggest that iron depletion plays an important role in palmitate-induced beta cell death through inducing ER stress. Therefore, attempts to block iron depletion might be able to prevent beta cell loss in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: The Problem Areas in Diabetes (PAID) scale is widely used for measuring diabetes-related emotional distress. There has been debate over the last 2 decades about the underlying factorial-construct validity of the PAID, with one- to four-factor structures being reported. A short form of the PAID, which comprises five items (PAID-5), was recently developed using Western patients with type 2 diabetes. This study measured the psychometric properties of the full and short forms of the PAID in Korean patients with type 2 diabetes, with the aim of determining which form is preferable.Methods: The PAID and PAID-5 were translated into Korean (K-PAID and K-PAID-5, respectively) using a forward-and-backward translation technique. The study participants were recruited from university hospitals. The factorial-construct, convergent, and known-groups validity, and internal-consistency and test-retest reliability of both the K-PAID and K-PAID-5 were evaluated.Results: For the K-PAID, confirmatory factor analysis revealed a marginal fit to the one-, two-, three-, and four-factor models. The three- and four-factor models of the K-PAID partially satisfied the internal-consistency and test-retest reliability, and convergent and known-groups validity. For the K-PAID-5, confirmatory factor analysis demonstrated an excellent fit to the one-factor model, with a Cronbach's alpha of 0.87 and an intraclass correlation coefficient of 0.89. The K-PAID-5 satisfied the convergent validity, as evaluated using the Center for Epidemiologic Studies Depression Scale and hemoglobin A1c. Known-groups validity by gender was also satisfied.Conclusions: The K-PAID-5 demonstrated excellent psychometric properties as a one-factor scale. The brevity of the K-PAID-5 represents a major advantage in a practical context in that it may impose a minimum burden upon patients with diabetes. [ABSTRACT FROM AUTHOR]

Highlights: [•] Inhibition of PC and CPT-1 induced apoptotic death in INS-1 beta cells. [•] PAA/Eto treatment increased damaged ER stress responses but decreased Akt survival signal. [•] JNK inhibitor or chemical chaperone was protective against PAA/Eto-induced cell death. [•] All attempts to increase the TCA cycle intermediate pool protected the INS-1 cells from PAA/Eto-induced death. [•] Toxicity induced by PPA/Eto was similar to HG/PA-induced glucolipotoxicity. [ABSTRACT FROM AUTHOR]

SIRT1 is an NAD+-dependent deacetylase that is implicated in prevention of many age-related diseases including metabolic disorders. As SIRT1 deacetylase activity is dependent on NAD+ levels and the development of compounds that directly activate SIRT1 has been controversial, indirectly activating SIRT1 through enhancing NAD+ bioavailability has received increasing attention. NAD+ levels are reduced in obesity and the aged, but the underlying mechanisms remain unclear. We recently showed that hepatic microRNA-34a (miR-34a), which is elevated in obesity, directly targets and decreases SIRT1 expression. Here, we further show that miR-34a reduces NAD+ levels and SIRT1 activity by targeting NAMPT, the rate-limiting enzyme for NAD+ biosynthesis. A functional binding site for miR-34a is present in the 3′ UTR of NAMPT mRNA. Hepatic overexpression of miR-34a reduced NAMPT/NAD+ levels, increased acetylation of the SIRT1 target transcriptional regulators, PGC-1α, SREBP-1c, FXR, and NF-κB, and resulted in obesity-mimetic outcomes. The decreased NAMPT/NAD+ levels were independent of miR-34a effects on SIRT1 levels as they were also observed in SIRT1 liver-specific knockout mice. Further, the miR-34a-mediated decreases were reversed by treatment with the NAD+ intermediate, nicotinamide mononucleotide. Conversely, antagonism of miR-34a in diet-induced obese mice restored NAMPT/NAD+ levels and alleviated steatosis, inflammation, and glucose intolerance. Anti-miR-34a-mediated increases in NAD+ levels were attenuated when NAMPT was downregulated. Our findings reveal a novel function of miR-34a in reducing both SIRT1 expression and activity in obesity. The miR-34a/NAMPT axis presents a potential target for treating obesity- and aging-related diseases involving SIRT1 dysfunction like steatosis and type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: With the increased incidence of diabetes mellitus, the importance of early intervention in prediabetes has been emphasized. We previously reported that fermented kimchi, a traditional Korean food, reduced body weight and improved metabolic factors in overweight participants. We hypothesized that kimchi and its fermented form would have beneficial effects on glucose metabolism in patients with prediabetes. Methods: A total of 21 participants with prediabetes were enrolled. During the first 8 weeks, they consumed either fresh (1-day-old) or fermented (10-day-old) kimchi. After a 4-week washout period, they switched to the other type of kimchi for the next 8 weeks. Results: Consumption of both types of kimchi significantly decreased body weight, body mass index, and waist circumference. Fermented kimchi decreased insulin resistance, and increased insulin sensitivity, QUICKI and disposition index values (p = 0.004 and 0.028, respectively). Systolic and diastolic blood pressure (BP) decreased significantly in the fermented kimchi group. The percentages of participants who showed improved glucose tolerance were 9.5 and 33.3% in the fresh and fermented kimchi groups, respectively. Conclusions: Consumption of kimchi had beneficial effects on glucose metabolism-related and anthropometric factors in participants with prediabetes. Fermented kimchi had additional effects on BP and insulin resistance/sensitivity. The percentage of participants who showed improvement in glucose tolerance was high in the fermented kimchi group. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Highlights: [•] Anti-oxidants are not protective against HG/PA-induced INS-1 beta cell death. [•] Supplementation of NAD+ is not protective against HG/PA-induced INS-1 cell death. [•] Activation of PARP is not involved in HG/PA-induced INS-1 cell death. [•] Knockdown of Sirt3 and Sirt4 reduced HG/PA-induced INS-1 cell death. [•] Nicotinamide is likely to protect HG/PA-induced glucolipotoxicity because of its inhibitory action on Sirts. [ABSTRACT FROM AUTHOR]