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Background/Aims: Reports on the association between sarcopenic visceral obesity and non-alcoholic fatty liver disease (NAFLD)-associated morbidities remain scarce. We investigated the association between sarcopenia and visceral obesity, and the influence of this association on hepatic and coronary comorbidities. Methods: The appendicular skeletal muscle mass to visceral fat area ratio (SV ratio) was evaluated using bioelectric impedance analysis. NAFLD and significant liver fibrosis were assessed using transient elastography, and high atherosclerotic cardiovascular disease (ASCVD) risk was defined as a 10-year ASCVD risk score >10%. Sarcopenia was defined as appendicular skeletal muscle mass adjusted by body mass index (

Abstract Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called ‘personalized lag time’. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Abstract We compared the prediction performance of machine learning-based undiagnosed diabetes prediction models with that of traditional statistics-based prediction models. We used the 2014–2020 Korean National Health and Nutrition Examination Survey (KNHANES) (N = 32,827). The KNHANES 2014–2018 data were used as training and internal validation sets and the 2019–2020 data as external validation sets. The receiver operating characteristic curve area under the curve (AUC) was used to compare the prediction performance of the machine learning-based and the traditional statistics-based prediction models. Using sex, age, resting heart rate, and waist circumference as features, the machine learning-based model showed a higher AUC (0.788 vs. 0.740) than that of the traditional statistical-based prediction model. Using sex, age, waist circumference, family history of diabetes, hypertension, alcohol consumption, and smoking status as features, the machine learning-based prediction model showed a higher AUC (0.802 vs. 0.759) than the traditional statistical-based prediction model. The machine learning-based prediction model using features for maximum prediction performance showed a higher AUC (0.819 vs. 0.765) than the traditional statistical-based prediction model. Machine learning-based prediction models using anthropometric and lifestyle measurements may outperform the traditional statistics-based prediction models in predicting undiagnosed diabetes.

Abstract Nonalcoholic fatty liver disease (NAFLD) occurs due to the accumulation of fat in the liver, leading to fatal liver diseases such as nonalcoholic steatohepatitis (NASH) and cirrhosis. Elucidation of the molecular mechanisms underlying NAFLD is critical for its prevention and therapy. Here, we observed that deubiquitinase USP15 expression was upregulated in the livers of mice fed a high-fat diet (HFD) and liver biopsies of patients with NAFLD or NASH. USP15 interacts with lipid-accumulating proteins such as FABPs and perilipins to reduce ubiquitination and increase their protein stability. Furthermore, the severity of NAFLD induced by an HFD and NASH induced by a fructose/palmitate/cholesterol/trans-fat (FPC) diet was significantly ameliorated in hepatocyte-specific USP15 knockout mice. Thus, our findings reveal an unrecognized function of USP15 in the lipid accumulation of livers, which exacerbates NAFLD to NASH by overriding nutrients and inducing inflammation. Therefore, targeting USP15 can be used in the prevention and treatment of NAFLD and NASH.

Abstract Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.

Background This study investigated the changes of fatty liver disease prevalence in general Korean population. Methods This study analyzed data from the Korean National Health Insurance Service from 2009 to 2017 that included individuals aged 20 years or older who had undergone a medical health examination. Fatty liver disease was assessed using the fatty liver index (FLI). The disease severity was defined by FLI cutoff, ≥30 as moderate, and ≥60 as severe fatty liver disease. Results The prevalence of Korean adults aged 20 years or over with fatty liver disease (FLI ≥60) increased from 13.3% in 2009 to 15.5% in 2017 (P for trend

AimHepatic ketogenesis is a key metabolic pathway that regulates energy homeostasis. Some related controversies exist regarding the pathogenesis of metabolic-associated fatty liver disease (MAFLD). We aimed to investigate whether intact ketogenic capacity could reduce the risk of MAFLD based on transient electrography (TE) in patients with newly diagnosed type 2 diabetes (T2D).MethodsA total of 361 subjects with newly diagnosed T2D were recruited and classified into two groups based on the median serum β-hydroxybutyrate (βHB) level, referred to as the intact and impaired ketogenesis groups. The glucometabolic relevance of ketogenic capacity and associations of the baseline serum β-HB and MAFLD assessed with TE were investigated.ResultsCompared to the impaired ketogenesis group, the intact ketogenesis group showed better insulin sensitivity, lower serum triglyceride levels, and higher glycated hemoglobin levels. The controlled attenuation parameter (CAP) was lower in the intact ketogenesis group without statistical significance (289.7 ± 52.1 vs. 294.5 ± 43.6; p=0.342) but the prevalence of moderate–severe steatosis defined by CAP ≥260 dB/m was significantly lower in the intact group. Moreover, intact ketogenesis was significantly associated with a lower risk of moderate–severe MAFLD after adjusting for potential confounders (adjusted odds ratio 0.55, 95% confidence interval 0.30–0.98; p=0.044).ConclusionIn drug-naïve, newly diagnosed T2D patients, intact ketogenesis predicted a lower risk of moderate–severe MAFLD assessed by TE.

Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2D) share common features, including insulin resistance. Brain insulin resistance has been implicated as a key factor in the pathogenesis of AD. Recent studies have demonstrated that anti-diabetic drugs sodium–glucose cotransporter-2 inhibitor (SGLT2-i) and dipeptidyl peptidase-4 inhibitor (DPP4-i) improve insulin sensitivity and provide neuroprotection. However, the effects of these two inhibitors on the brain metabolism and insulin resistance remain uninvestigated. We developed a T2D–AD mouse model using a high-fat diet (HFD) for 19 weeks along with a single dose of streptozotocin (100 mg/kg, intraperitoneally) at the fourth week of HFD initiation. Subsequently, the animals were treated with SGLT2-i (empagliflozin, 25 mg/kg/day orally [p.o.]) and DPP4-i (sitagliptin, 100 mg/kg/day p.o.) for 7 weeks. Subsequently, behavioral tests were performed, and the expression of insulin signaling, AD-related, and other signaling pathway proteins in the brain were examined. T2D–AD mice not only showed increased blood glucose levels and body weight but also insulin resistance. SGLT2-i and DPP4-i effectively ameliorated insulin sensitivity and reduced body weight in these mice. Furthermore, SGLT2-i and DPP4-i significantly improved hippocampal-dependent learning, memory, and cognitive functions in the T2D–AD mouse model. Interestingly, SGLT2-i and DPP4-i reduced the hyperphosphorylated tau (pTau) levels and amyloid β (Aβ) accumulation and enhanced brain insulin signaling. SGLT2-i reduced pTau accumulation through the angiotensin converting enzyme-2/angiotensin (1−7)/ mitochondrial assembly receptor axis, whereas DPP4-i reduced Aβ accumulation by increasing insulin-degrading enzyme levels. These findings suggest that SGLT2-i and DPP4-i prevent AD-like pathology and cognitive dysfunction in T2D mice potentially through affecting brain insulin signaling via different mechanisms.

Background We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value

Abstract Magnetoencephalography (MEG) is a functional neuroimaging technique that noninvasively detects the brain magnetic field from neuronal activations. Conventional MEG measures brain signals using superconducting quantum interference devices (SQUIDs). SQUID-MEG requires a cryogenic environment involving a bulky non-magnetic Dewar flask and the consumption of liquid helium, which restricts the variability of the sensor array and the gap between the cortical sources and sensors. Recently, miniature optically pumped magnetometers (OPMs) have been developed and commercialized. OPMs do not require cryogenic cooling and can be placed within millimeters from the scalp. In the present study, we arranged six OPM sensors on the temporal area to detect auditory-related brain responses in a two-layer magnetically shielded room. We presented the auditory stimuli of 1 kHz pure-tone bursts with 200 ms duration and obtained the M50 and M100 components of auditory-evoked fields. We delivered the periodic stimuli with a 40 Hz repetition rate and observed the gamma-band power changes and inter-trial phase coherence of auditory steady-state responses at 40 Hz. We found that the OPM sensors have a performance comparable to that of conventional SQUID-MEG sensors, and our results suggest the feasibility of using OPM sensors for functional neuroimaging and brain–computer interface applications.

Background/Aims: Metabolic dysfunction associated fatty liver disease (MAFLD) has recently been introduced to compensate for the conventional concept of nonalcoholic fatty liver disease (NAFLD). We explored whether fibrotic burden determines the risk of atherosclerotic cardiovascular disease (ASCVD) among subjects with MAFLD. Methods: We recruited 9,444 participants from the Korea National Health and Nutrition Examination Survey (2008 to 2011). Liver fibrosis was identified using the fibrosis-4 (FIB-4) index and NAFLD fibrosis score. The 10-year ASCVD risk score (>10%) was used to determine a high probability ASCVD risk. For sensitivity analysis, propensity score matching was assessed to subjects with aged 40 to 75 years free from ASCVD. Results: The prevalence of MAFLD was 38.0% (n=3,592). The ASCVD risk scores stratified in quartile were positively correlated to MAFLD and FIB-4 defined-significant liver fibrosis (p for trend

Abstract Aims/Introduction We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. Materials and Methods Individuals with adult type 2 diabetes who underwent consecutive 2‐year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. Results Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non‐smokers and non‐drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23–1.34; hazard ratio 1.22, 95% confidence interval 1.15–1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77–0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose‐dependent fashion (P for trend

Abstract Background Recent studies have reported improved diastolic function in patients administered sodium-glucose cotransporter 2 inhibitors (SGLT2i). We aimed to investigate the effect of dapagliflozin on left ventricular (LV) diastolic function in a diabetic animal model and to determine the molecular and cellular mechanisms underlying its function. Methods A total of 30 male New Zealand white rabbits were randomized into control, diabetes, or diabetes+dapagliflozin groups (n = 10/per each group). Diabetes was induced by intravenous alloxan. Cardiac function was evaluated using echocardiography. Myocardial samples were obtained for histologic and molecular evaluation. For cellular evaluation, fibrosis-induced cardiomyoblast (H9C2) cells were obtained, and transfection was performed for mechanism analysis (serum and glucocorticoid-regulated kinase 1 (SGK1) signaling analysis). Results The diabetes+dapagliflozin group showed attenuation of diastolic dysfunction compared with the diabetes group. Dapagliflozin inhibited myocardial fibrosis via inhibition of SGK1 and epithelial sodium channel (ENaC) protein, which was observed both in myocardial tissue and H9C2 cells. In addition, dapagliflozin showed an anti-inflammatory effect and ameliorated mitochondrial disruption. Inhibition of SGK1 expression by siRNA decreased and ENaC and Na+/H+ exchanger isoform 1 (NHE1) expression was confirmed as significantly reduced as siSGK1 in the diabetes+dapagliflozin group. Conclusions Dapagliflozin attenuated left ventricular diastolic dysfunction and cardiac fibrosis via regulation of SGK1 signaling. Dapagliflozin also reduced macrophages and inflammatory proteins and ameliorated mitochondrial disruption.

Abstract The α-glucosidase inhibitor (α-GI) delays the intestinal absorption of glucose, which reduces postprandial hepatic glucose intake. This mechanism is considered to be effective in treating non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effect of voglibose, an α-glucosidase inhibitor, on high-fat, high-fructose (HFHFr) diet-induced NAFLD models. Seven-week-old male C57BL/6J mice were randomly placed in a chow diet group or an HFHFr diet group. After 10 weeks, mice in the HFHFr group were randomly assigned to one of three groups: HFHFr diet with vehicle, HFHFr with voglibose, or HFHFr with pioglitazone. Each diet and treatment was continued for 10 weeks. The HFHFr diet induced severe NAFLD in terms of steatosis, hepatitis, and fibrosis. Administration of voglibose improved all aspects of NAFLD, comparable to those of pioglitazone, a positive control. In voglibose-treated mice, gene expressions of hepatic lipogenesis markers were significantly downregulated. In the in vitro experiment, reducing the influx of glucose into hepatocytes significantly reduced steatosis and de novo lipogenesis even in the presence of sufficient fructose and fat, demonstrating that the mechanism of voglibose could be effective in treating HFHFr diet-induced NAFLD. These results indicate that voglibose improves HFHFr diet-induced NAFLD by suppressing hepatic de novo lipogenesis.

Background Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy. Methods We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes. Results Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway. Conclusion DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.

Necroptosis is a type of cell death with excessive inflammation and organ damage in various human diseases. Although abnormal necroptosis is common in patients with neurodegenerative, cardiovascular, and infectious diseases, the mechanisms by which O-GlcNAcylation contributes to the regulation of necroptotic cell death are poorly understood. In this study, we reveal that O-GlcNAcylation of RIPK1 (receptor-interacting protein kinase1) was decreased in erythrocytes of the mouse injected with lipopolysaccharide, resulting in the acceleration of erythrocyte necroptosis through increased formation of RIPK1-RIPK3 complex. Mechanistically, we discovered that O-GlcNAcylation of RIPK1 at serine 331 in human (corresponding to serine 332 in mouse) inhibits phosphorylation of RIPK1 at serine 166, which is necessary for the necroptotic activity of RIPK1 and suppresses the formation of the RIPK1-RIPK3 complex in Ripk1-/- MEFs. Thus, our study demonstrates that RIPK1 O-GlcNAcylation serves as a checkpoint to suppress necroptotic signaling in erythrocytes.

A novel displacement ventilation system (DVS) was designed using a four-way cassette fan coil unit (FCU) and air purifiers (APs) for supplying clean air. The proposed DVS in this study involved drawing indoor air through the FCU and diffusers installed in the ceiling, controlling air temperature using the FCU, and then discharging it back into the office through the APs placed on the floor. The comparative ventilation system considered was the typical mixing ventilation system (MVS) that intakes and exhausts indoor air using diffusers installed on the ceiling. The local mean age of air was used as an index to compare indoor air quality between DVS and MVS under winter heating conditions. It was found that the DVS was more effective in improving indoor air quality in winter than the MVS. Moreover, compared to the MVS, utilizing the DVS designed in this study resulted in the advantage of a much more uniform air temperature variation in the office space. Therefore, it is anticipated that modifying the structure of an indoor space with an FCU installed in the ceiling and APs on the floor to use the DVS designed in this study would greatly assist in enhancing indoor air quality.

Background Nonalcoholic fatty liver disease (NAFLD) is associated with chronic kidney disease (CKD). However, the causal relationship between NAFLD and CKD is uncertain, particularly in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the association between the presence and severity of NAFLD and incident CKD in patients with T2DM. Methods In this longitudinal cohort study of patients with T2DM, 3,188 patients with preserved renal function were followed up for the occurrence of incident CKD. NAFLD was defined as the presence of hepatic steatosis on ultrasonography, without any other causes of chronic liver disease. Advanced liver fibrosis of NAFLD was defined as a fibrosis-4 index ≥2.67. CKD was defined as an estimated glomerular filtration rate

Abstract This study aimed to determine whether the patterns of diabetic complications differed when patients with type 2 diabetes mellitus (T2DM) were simply classified according to insulin sensitivity and beta-cell function. This observational study included 8861 patients with T2DM who underwent concurrent testing for fasting glucose, fasting insulin, and one or more diabetic complications. We categorized the patients into four groups according to insulin sensitivity and beta-cell function. Compared with the reference group (mild insulin resistance and beta-cell dysfunction), the “severe beta-cell dysfunction” group had lower odds of chronic kidney disease [adjusted odds ratios (aOR) 0.611]. The “severe insulin resistance” group had higher odds of carotid artery plaque presence (aOR 1.238). The “severe insulin resistance and beta-cell dysfunction” group had significantly higher odds of large fiber neuropathy (aOR 1.397, all p

AimsThe ketogenic pathway is an effective mechanism by which the liver disposes of fatty acids (FAs) to the peripheral tissues. Impaired ketogenesis is presumed to be related to the pathogenesis of metabolic-associated fatty liver disease (MAFLD), but the results of previous studies have been controversial. Therefore, we investigated the association between ketogenic capacity and MAFLD in subjects with type 2 diabetes (T2D).MethodsA total of 435 subjects with newly diagnosed T2D was recruited for the study. They were classified into two groups based on median serum β-hydroxybutyrate (β-HB) level: intact vs. impaired ketogenesis groups. The associations of baseline serum β-HB and MAFLD indices of hepatic steatosis index, NAFLD liver fat score (NLFS), Framingham Steatosis index (FSI), Zhejian University index, and Chinese NAFLD score were investigated.ResultsCompared to the impaired ketogenesis group, the intact ketogenesis group showed better insulin sensitivity, lower serum triglyceride level, and higher low-density lipoprotein-cholesterol and glycated hemoglobin levels. Serum levels of liver enzymes were not different between the two groups. Of the hepatic steatosis indices, NLFS (0.8 vs. 0.9, p=0.045) and FSI (39.4 vs. 47.0: p=0.041) were significantly lower in the intact ketogenesis group. Moreover, intact ketogenesis was significantly associated with lower risk of MAFLD as calculated by FSI after adjusting for potential confounders (adjusted odds ratio 0.48, 95% confidence interval 0.25-0.91, p=0.025).ConclusionsOur study suggests that intact ketogenesis might be associated with decreased risk of MAFLD in T2D.

Brassica napus is an oilseed plant that is mostly used to produce edible oils, industrial oils, modified lipids and biofuels. The number of varieties/cultivars is high for the species, owing to their higher level of economic use. The aim of this study is to assess the use of visible-near infrared (Vis-NIR) spectroscopy in combination with multiple chemometric methods that have been explored for the discrimination of eight Brassica napus varieties in Korea. In this study, the spectra from leaves of the eight B. napus varieties were measured in the Vis-NIR spectra in the range of 325–1075 nm with a stepping of 1.5 nm in reflectance mode. The spectral data were preprocessed with three different preprocessing methods and eight different chemometric analyses were used for effective discrimination. After the outlier detection, the samples were split into two sets, one serving as a calibration set and the remaining one as a validation set. When using multiple preprocessing and chemometric methods for the discrimination, the maximum classification accuracy was witnessed in the combination of standard normal variate and support vector machine up to 98.2 %. The use of Savitzky-Golay filter smoothing as a preprocessing method had the best and most satisfactory discrimination of all other chemometric methods. The results suggest that the use of handheld Vis-NIR spectroscopy in combination with chemometric approaches can be used as an effective tool for the discrimination of B. napus varieties in the field.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear. Methods: Data from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥-0.640. ASCVD risk was evaluated using the American College of Cardiology/ American Heart Association guidelines. Results: The frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p

Background Risk assessment tools have been actively studied, and they summarize key predictors with relative weights/importance for a disease. Currently, standardized screening scores for type 2 diabetes mellitus (DM) and chronic kidney disease (CKD)—two key global health problems—are available in United States and Korea. We aimed to compare and evaluate screening scores for DM (or combined with prediabetes) and CKD, and assess the risk in contemporary United States and Korean populations. Methods Four (2×2) models were evaluated in the United States-National Health and Nutrition Examination Survey (NHANES 2015–2018) and Korea-NHANES (2016–2018)—8,928 and 16,209 adults. Weighted statistics were used to describe population characteristics. We used logistic regression for predictors in the models to assess associations with study outcomes (undiagnosed DM and CKD) and diagnostic measures for temporal and cross-validation. Results Korean adult population (mean age 47.5 years) appeared to be healthier than United States counterpart, in terms of DM and CKD risks and associated factors, with exceptions of undiagnosed DM, prediabetes and prehypertension. Models performed well in own country and external populations regarding predictor-outcome association and discrimination. Risk tests (high vs. low) showed area under the curve >0.75, sensitivity >84%, specificity >45%, positive predictive value >8%, and negative predictive value >99%. Discrimination was better for DM, compared to the combined outcome of DM and prediabetes, and excellent for CKD due to age. Conclusion Four easy-to-use screening scores for DM and CKD are well-validated in contemporary United States and Korean populations. Prevention of DM and CKD may serve as first-step in public health, with these self-assessment tools as basic tools to help health education and disparity.

Abstract Background The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD). Methods A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change. Results Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104). Conclusions Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population. Trial registration The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, can progress to cirrhosis, hepatocellular carcinoma, and death. Nevertheless, the current treatment for NAFLD/NASH is limited to lifestyle modifications, and no drugs are currently officially approved as treatments for NASH. Many global pharmaceutical companies are pursuing the development of medications for the treatment of NASH, and results from phase 2 and 3 clinical trials have been published in recent years. Here, we review data from these recent clinical trials and reports on the efficacy of newly developed antidiabetic drugs in NASH treatment.

Background Non-alcoholic steatohepatitis is closely associated with the progression of diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). We investigated whether urinary N-acetyl-β-D-glucosaminidase (u-NAG), an early renal tubular damage biomarker in DKD, could be related to the degree of hepatic fibrosis in patients with T2DM. Methods A total of 300 patients with T2DM were enrolled in this study. Hepatic steatosis and fibrosis were determined using transient elastography. The levels of urinary biomarkers, including u-NAG, albumin, protein, and creatinine, and glucometabolic parameters were measured. Results Based on the median value of the u-NAG to creatinine ratio (u-NCR), subjects were divided into low and high u-NCR groups. The high u-NCR group showed a significantly longer duration of diabetes, worsened hyperglycemia, and a more enhanced hepatic fibrosis index. A higher u-NCR was associated with a greater odds ratio for the risk of higher hepatic fibrosis stage (F2: odds ratio, 1.99; 95% confidence interval [CI], 1.04 to 3.82). Also, u-NCR was an independent predictive marker for more advanced hepatic fibrosis, even after adjusting for several confounding factors (β=1.58, P

Background The prevalence of non-alcoholic fatty liver disease (NAFLD) has rapidly increased worldwide. The aim of this study was to investigate whether there is an independent relationship between regional fat distribution, especially leg fat mass, and the presence of NAFLD using nationally representative data in Korea. Methods This cross-sectional study analyzed data from 14,502 participants in the Korea National Health and Nutrition Examination Survey 2008 to 2011. Total fat mass, leg fat mass, and appendicular skeletal muscle mass were measured by dual-energy X-ray absorptiometry. Validated NAFLD prediction models and scoring systems for hepatic fibrosis were used. Results The leg fat to total fat (LF/TF) ratio showed a negative relationship with many factors, including body mass index, waist circumference, blood pressure, fasting blood glucose, and liver enzyme levels. When the LF/TF ratio and indices of hepatic steatosis were stratified by quartiles, the LF/TF ratio showed a negative correlation with the scoring systems that were used. The LF/TF ratio showed better accuracy in predicting NAFLD than total fat mass or leg fat mass alone. After adjusting for various traditional and lifestyle factors, a low LF/TF ratio remained a risk factor for NAFLD. Among NAFLD subjects, the LF/TF ratio showed a negative relationship with hepatic fibrosis. Conclusion A lower LF/TF ratio was markedly associated with a higher risk of hepatic steatosis and advanced hepatic fibrosis using various predictive models in a Korean population. Therefore, the LF/TF ratio could be a useful anthropometric parameter to predict NAFLD or advanced hepatic fibrosis.

Abstract Background In this prospective, multicenter, non-comparative observational study, the effectiveness and safety of the triple single-pill combination (SPC) of olmesartan/amlodipine/hydrochlorothiazide (OM/AML/HCTZ) were evaluated in a real clinical practice setting in Korean patients with essential hypertension. Methods A total of 3752 patients were enrolled and followed for 12 months after administration of OM/AML/HCTZ. Primary endpoint was change from baseline to month 6 in the mean systolic blood pressure (SBP). Secondary endpoints included changes from baseline in the mean SBP at month 3, 9, 12 and the mean diastolic blood pressure (DBP) at month 3, 6, 9, 12; changes in the mean SBP/DBP according to age and underlying risk factors; and blood pressure control rate (%) at different time points. Adherence to and satisfaction with OM/AML/HCTZ treatment among patients and physicians were assessed by medication possession ratio (MPR) and numeric rating scale, respectively, as exploratory endpoints. Safety was evaluated by the incidence and severity of adverse events (AEs) as well as the discontinuation rate due to AEs. Results OM/AML/HCTZ administration led to significant reductions in the mean SBP/DBP by 11.5/6.6, 12.3/7.0, 12.3/7.2, and 12.8/7.4 mmHg from baseline to month 3, 6, 9 and 12, respectively (P

Background Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that exhibit multiple extraglycemic effects. However, there are conflicting results regarding the effects of SGLT2 inhibition on energy expenditure and thermogenesis. Therefore, we investigated the effect of ipragliflozin (a selective SGLT2 inhibitor) on energy metabolism. Methods Six-week-old male 129S6/Sv mice with a high propensity for adipose tissue browning were randomly assigned to three groups: normal chow control, 60% high-fat diet (HFD)-fed control, and 60% HFD-fed ipragliflozin-treated groups. The administration of diet and medication was continued for 16 weeks. Results The HFD-fed mice became obese and developed hepatic steatosis and adipose tissue hypertrophy, but their random glucose levels were within the normal ranges; these features are similar to the metabolic features of a prediabetic condition. Ipragliflozin treatment markedly attenuated HFD-induced hepatic steatosis and reduced the size of hypertrophied adipocytes to that of smaller adipocytes. In the ipragliflozin treatment group, uncoupling protein 1 (Ucp1) and other thermogenesis-related genes were significantly upregulated in the visceral and subcutaneous adipose tissue, and fatty acid oxidation was increased in the brown adipose tissue. These effects were associated with a significant reduction in the insulin-to-glucagon ratio and the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) pathway in the liver and adipose tissue. Conclusion SGLT2 inhibition by ipragliflozin showed beneficial metabolic effects in 129S6/Sv mice with HFD-induced obesity that mimics prediabetic conditions. Our data suggest that SGLT2 inhibitors, through their upregulation of energy expenditure, may have therapeutic potential in prediabetic obesity.

Background Nonalcoholic fatty liver disease (NAFLD) is the most prevalent cause of chronic liver disease worldwide. Type 2 diabetes mellitus (T2DM) is a risk factor that accelerates NAFLD progression, leading to fibrosis and cirrhosis. Thus, here we aimed to develop a simple model to predict the presence of NAFLD based on clinical parameters of patients with T2DM. Methods A total of 698 patients with T2DM who visited five medical centers were included. NAFLD was evaluated using transient elastography. Univariate logistic regression analyses were performed to identify potential contributors to NAFLD, followed by multivariable logistic regression analyses to create the final prediction model for NAFLD. Results Two NAFLD prediction models were developed, with and without serum biomarker use. The non-laboratory model comprised six variables: age, sex, waist circumference, body mass index (BMI), dyslipidemia, and smoking status. For a cutoff value of ≥60, the prediction accuracy was 0.780 (95% confidence interval [CI], 0.743 to 0.817). The second comprehensive model showed an improved discrimination ability of up to 0.815 (95% CI, 0.782 to 0.847) and comprised seven variables: age, sex, waist circumference, BMI, glycated hemoglobin, triglyceride, and alanine aminotransferase to aspartate aminotransferase ratio. Our non-laboratory model showed non-inferiority in the prediction of NAFLD versus previously established models, including serum parameters. Conclusion The new models are simple and user-friendly screening methods that can identify individuals with T2DM who are at high-risk for NAFLD. Additional studies are warranted to validate these new models as useful predictive tools for NAFLD in clinical practice.

A ketogenic diet (KD) is known to have beneficial health effects. Various types of KD interventions have been applied to manage metabolic syndrome based on modification of diet parameters such as duration of intervention, macronutrient components, and total calories. Nevertheless, the beneficial health impact of isocaloric KD is largely unknown, especially in healthy subjects. The present study investigated the acute effects of a 3-day isocaloric KD. In this non-randomized intervention study, we recruited 15 healthy volunteers aged 24-38 years (7 men and 8 women) and placed them on an isocaloric KD restricting intake of carbohydrates but not energy (75% fat, 20% protein, 5% carbohydrate) for 3 days. Biochemical profiles and laboratory measurements were performed. Peripheral blood monocular cells were cultured, and measured cell stimulated cytokines. After short-term isocaloric KD, subjects lost body weight and serum free fatty acid levels were increased. These results accompanied elevated serum β-hydroxybutyrate (BHB) concentration and fibroblast growth factor 21 (FGF21) levels and improved insulin sensitivity. Regarding the direct effect of BHB on inflammasome activation, interleukin-1β (IL-1β) and tumor necrosis factor-α secretion in response to adenosine triphosphate or palmitate stimulation in human macrophages decreased significantly after isocaloric KD. In ex-vivo experiments with macrophages, both FGF21 and BHB further reduced IL-1β secretion compared to either BHB or FGF21 alone. The inhibitory effect of FGF21 on IL-1β secretion was blunted with bafilomycin treatment, which blocked autophagy flux. In conclusion, isocaloric KD for 3 days is a promising approach to improve metabolic and inflammatory status.Clinical Trial Registrationclinicaltrials.gov (NCT02964572).

Abstract Background Metabolic diseases, including type 2 diabetes, have long been considered incurable, chronic conditions resulting from a variety of pathological conditions in obese patients. Growing evidence suggests the Wnt/β‐catenin pathway is a major pathway in adipose tissue remodelling, pancreatic β‐cell regeneration and energy expenditure through regulation of key metabolic target genes in various tissues. CXXC5‐type zinc finger protein 5 (CXXC5) is identified negative feedback regulator of the Wnt/β‐catenin pathway that functions via Dishevelled (Dvl) binding. Methods Expression level of CXXC5 was characterised in clinical samples and diabetes‐induced mice model. Diabetes‐induced mice model was established by using high‐fat diet (HFD). HFD‐fed mice treated with KY19334, a small molecule inhibiting CXXC5‐Dvl protein–protein interaction (PPI), was used to assess the role of CXXC5 in metabolic diseases. Results Here, we show that CXXC5 is overexpressed with suppression of Wnt/β‐catenin signalling in visceral adipose tissues of patients with obesity‐related diabetes. Meanwhile, Cxxc5−/− mice fed an HFD exhibited resistance to metabolic dysregulation. KY19334 restores the lowered Wnt/β‐catenin signalling and reverses metabolic abnormalities as observed in HFD‐fed Cxxc5−/− mice. Administration of KY19334 on HFD‐fed mice had a long‐lasting glucose‐controlling effect through remodelling of adipocytes and regeneration of pancreatic β‐cells. Conclusion Overall, the inhibition of CXXC5 function by small molecule‐mediated interference of Dvl binding is a potential therapeutic strategy for the treatment of obesity‐related diabetes.

During the extensive forays for discovering the biodiversity of phytopathogenic fungi in Korea, powdery mildew-affected purple coneflowers (Echinacea purpurea) were frequently found. Since 2004, nine samples have been deposited in the Korea University Herbarium. The initial symptoms include white, evanescent mycelia and irregular patches on mature leaves. Mild symptoms in the form of discolored lesions are also noticed on the stem and petal of the affected plants. Based on the morphological characteristics of the anamorph and the phylogenetic analysis of the internal transcribed spacers (ITS) and large subunit (LSU) rDNA sequences, the causal fungus was identified as Podosphaera xanthii. This is the first report that identifies the causal agent of powdery mildew disease affecting purple coneflower in Korea.

Abstract Background There is increasing concern regarding cardiovascular risk in individuals with non-alcoholic fatty liver disease. This study was conducted to evaluate whether hepatic steatosis with or without fibrosis is associated with the progression of carotid atherosclerosis in patients with type 2 diabetes. Methods From a longitudinal cohort, we enrolled 1120 patients with type 2 diabetes who underwent repeated carotid artery ultrasonography every 1–2 years. Ultrasonographic findings at baseline and after 6–8 years were compared. Presence of hepatic steatosis was mainly assessed by abdominal ultrasonography; patients with hepatic steatosis were further evaluated for hepatic fibrosis according to fibrosis-4 index. We investigated the association between liver status and atherosclerosis progression. Results Of 1120 patients, 636 (56.8%) were classified as having hepatic steatosis at baseline. After 6–8 years, 431 (38.5%) showed atherosclerosis progression. Hepatic steatosis was significantly associated with atherosclerosis progression (adjusted odds ratio[AOR]: 1.370, 95% CI 1.025–1.832; p

This clinical practice position statement, a product of the Fatty Liver Research Group of the Korean Diabetes Association, proposes recommendations for the diagnosis, progression and/or severity assessment, management, and follow-up of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Patients with both T2DM and NAFLD have an increased risk of non-alcoholic steatohepatitis (NASH) and fibrosis and a higher risk of cardiovascular diseases and diabetic complications compared to those without NAFLD. With regards to the evaluation of patients with T2DM and NAFLD, ultrasonography-based stepwise approaches using noninvasive biomarker models such as fibrosis-4 or the NAFLD fibrosis score as well as imaging studies such as vibration-controlled transient elastography with controlled attenuation parameter or magnetic resonance imaging-proton density fat fraction are recommended. After the diagnosis of NAFLD, the stage of fibrosis needs to be assessed appropriately. For management, weight reduction achieved by lifestyle modification has proven beneficial and is recommended in combination with antidiabetic agent(s). Evidence that some antidiabetic agents improve NAFLD/NASH with fibrosis in patients with T2DM is emerging. However, there are currently no definite pharmacologic treatments for NAFLD in patients with T2DM. For specific cases, bariatric surgery may be an option if indicated.

SGLT2 inhibitors, a class of type 2 diabetes medication, reduce cardiovascular events in patients beyond expectation from blood sugar control. Here the authors report a randomized controlled trial showing that SGLT2 inhibitors reduce inflammasome activation in peripheral macrophages, which may contribute to the cardiovascular protection.

BackgroundImpaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.MethodsWe analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.ResultsLV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).ConclusionsLiver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

BackgroundCardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.MethodsThis randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and

Objective: This study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM). Methods: This observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6–8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed. Results: Among 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392–0.870; p=0.008). Age (p

OBJECTIVES The purpose of this study was (1) to examine whether the addition of resting heart rate (RHR) to the existing undiagnosed diabetes mellitus (UnDM) prediction model would improve predictability, and (2) to develop and validate UnDM prediction models by using only easily assessable variables such as gender, RHR, age, and waist circumference (WC). METHODS Korea National Health and Nutrition Examination Survey (KNHANES) 2010, 2012, 2014, 2016 data were used to develop the model (model building set, n=19,675), while the data from 2011, 2013, 2015, 2017 were used to validate the model (validation set, n=19,917). UnDM was defined as a fasting glucose level ≥126 mg/dL or glycated hemoglobin ≥6.5%; however, doctors have not diagnosed it. Statistical package for the social sciences logistic regression analysis was used to determine the predictors of UnDM. RESULTS RHR, age, and WC were associated with UnDM. When RHR was added to the existing model, sensitivity was reduced (86 vs. 73%), specificity was increased (49 vs. 65%), and a higher Youden index (35 vs. 38) was expressed. When only gender, RHR, age, and WC were used in the model, a sensitivity, specificity, and Youden index of 70%, 67%, and 37, respectively, were observed. CONCLUSIONS Adding RHR to the existing UnDM prediction model improved specificity and the Youden index. Furthermore, when the prediction model only used gender, RHR, age, and WC, the outcomes were not inferior to those of the existing prediction model.

The global climate change, including increases in temperature and precipitation, may exacerbate the invasion by P. hysterophorus. Here, MaxEnt modeling was performed to predict P. hysterophorus distribution worldwide and in South Korea under the current and future climate global climate changes, including increases in temperature and precipitation. Under the current climate, P. hysterophorus was estimated to occupy 91.26%, 83.26%, and 62.75% of the total land area of Australia, South America, and Oceania, respectively. However, under future climate scenarios, the habitat distribution of P. hysterophorus would show the greatest change in Europe (56.65%) and would extend up to 65°N by 2081–2100 in South Korea, P. hysterophorus currently potentially colonizing 2.24% of the land area, particularly in six administrative divisions. In the future, P. hysterophorus would spread rapidly, colonizing all administrative divisions, except Incheon, by 2081–2100. Additionally, the southern and central regions of South Korea showed greater habitat suitability than the northern region. These findings suggest that future climate change will increase P. hysterophorus distribution both globally and locally. Therefore, effective control and management strategies should be employed around the world and in South Korea to restrict the habitat expansion of P. hysterophorus.

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention.Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD.Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20–2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74–4.80; P < 0.001].Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.

Alzheimer’s disease (AD) is characterized by memory loss and cognitive decline. Additionally, abnormal extracellular amyloid plaques accumulation and nerve damage caused by intracellular neurofibrillary tangles, and tau protein are characteristic of AD. Furthermore, AD is associated with oxidative stress, impaired mitochondrial structure and function, denormalization, and inflammatory responses. Recently, besides the amyloid β hypothesis, another hypothesis linking AD to systemic diseases has been put forth by multiple studies as a probable cause for AD. Particularly, type 2 diabetes mellitus (T2DM) and its features, including hyperinsulinemia, and chronic hyperglycemia with an inflammatory response, have been shown to be closely related to AD through insulin resistance. The brain cannot synthesize or store glucose, but it does require glucose, and the use of glucose in the brain is higher than that in any other organ in the mammalian body. One of the therapeutic drugs for T2DM, dipeptidyl peptidase-4 (DPP-4) inhibitor, suppresses the degradation of incretins, glucagon-like peptides and glucose-dependent insulinotropic peptide. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, recently used in T2DM treatment, have a unique mechanism of action via inhibition of renal glucose reabsorption, and which is different from the mechanisms of previously used medications. This manuscript reviews the pathophysiological relationship between the two diseases, AD and T2DM, and the pharmacological effects of therapeutic T2DM drugs, especially DPP-4 inhibitors, and SGLT2 inhibitors.

Brown mustard (Brassica juncea (L.) is an important oilseed crop that is mostly used to produce edible oils, industrial oils, modified lipids and biofuels in subtropical nations. Due to its higher level of commercial use, the species has a huge array of varieties/cultivars. The purpose of this study is to evaluate the use of visible near-infrared (Vis-NIR) spectroscopy in combination with multiple chemometric approaches for distinguishing four B. juncea varieties in Korea. The spectra from the leaves of four different growth stages of four B. juncea varieties were measured in the Vis-NIR range of 325–1075 nm with a stepping of 1.5 nm in reflectance mode. For effective discrimination, the spectral data were preprocessed using three distinct approaches, and eight different chemometric analyses were utilized. After the detection of outliers, the samples were split into two groups, one serving as a calibration set and the other as a validation set. When numerous preprocessing and chemometric approaches were applied for discriminating, the combination of standard normal variate and deep learning had the highest classification accuracy in all the growth stages achieved up to 100%. Similarly, few other chemometrics also yielded 100% classification accuracy, namely, support vector machine, generalized linear model, and the random forest. Of all the chemometric preprocessing methods, Savitzky–Golay filter smoothing provided the best and most convincing discrimination. The findings imply that chemometric methods combined with handheld Vis-NIR spectroscopy can be utilized as an efficient tool for differentiating B. juncea varieties in the field in all the growth stages.

This study aimed to examine the effect of taurolidine irrigation on preventing surgical site infection by comparing the spinal infection rate after spinal fusion surgery using vancomycin powder application and taurolidine irrigation. Of 1081 participants, 369 underwent taurolidine irrigation, 221 underwent vancomycin powder application, and 491 were controls. Of the 20 surgical site infections (1.85%), 14 occurred in the control group (2.85%), 5 in the vancomycin group (2.26%), and 1 (0.27%) in the taurolidine group. Among the various variables, age at the time of surgery, smoking, surgical site, and hemovac removal time were significant in the univariate logistic regression. The final result was derived after variable selection using the stepwise method. In the univariate model, the odds ratios were 0.09 and 0.79 in each of the vancomycin and taurolidine groups compared to that of the control group. In the multivariate model, the odds ratios were 0.09 and 0.83 in each of the vancomycin and taurolidine groups compared to that of the control group. The preventive effect of vancomycin powder application was not statistically significant. However, the vancomycin group showed a less effective tendency than the taurolidine group. Taurolidine irrigation may be a good substitute for the vancomycin powder application.