ABSTRACT
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 <0.001). The increase in fatty liver disease prevalence was prominent in men (from 20.5% to 24.2%) and the young age (20 to 39 years) group (from 12.8% to 16.4%) (P for interaction <0.001). The prevalence of fatty liver disease was the highest in type 2 diabetes mellitus (T2DM, 29.6%) population compared to that of prediabetes or normoglycemia (10.0% and 21.8%) in 2017. The prevalence of fatty liver disease had statistically increased in individuals with T2DM and prediabetes (P for trend <0.001). Its prevalence increased more steeply in the young-aged population with T2DM, from 42.2% in 2009 to 60.1% in 2017. When applying a lower FLI cutoff (≥30) similar results were observed. @*Conclusion@#The prevalence of fatty liver disease in the Korean population has increased. Individuals who are young, male, and have T2DM are vulnerable to fatty liver disease.
ABSTRACT
Purpose@#To compare the corneal epithelial wound healing effects of RCI001, Solcoseryl, and polydeoxyribonucleotide (PDRN) in a rat alkali burn model. @*Methods@#In 40 male Sprague-Dawley rats, we induced alkali burn using filter paper soaked in 0.2N sodium hydroxide. The rats were then treated with topical 0.5% RCI001, 1.0% RCI001, Solcoseryl, or PDRN twice a day for 2 weeks. Corneal epithelial integrity and epithelial healing rate were measured at day 0, 3, 5, 7, 10, and 14. Histologic and immunohistochemistry findings were also assessed. @*Results@#Both the 0.5% and 1.0% RCI001 groups showed significantly more epithelial healing compared to the control group at day 5, 7, 10, and 14 (each p < 0.05). No statistical difference was found between the 0.5% and 1.0% RCI001 groups. Neither the Solcoseryl nor the PDRN groups showed a significant difference from the control. RCI001 treatment resulted in significantly reduced stromal edema, and a trend towards less inflammatory cell infiltration. @*Conclusions@#Topical application of RCI001 showed enhanced corneal epithelial wound healing in the murine corneal alkali burn model, presumably by suppressing inflammation. Meanwhile, Solcoseryl and PDRN did not show sufficient therapeutic effects compared to RCI001.
ABSTRACT
Background@#In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX). @*Methods@#DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements. @*Results@#The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation. @*Conclusion@#P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release.
ABSTRACT
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 <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. @*Results@#Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. @*Conclusion@#NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.
ABSTRACT
Background@#The most common cause of neurological complications after a biportal endoscopic spine surgery (BESS) is postoperative spinal epidural hematomas (POSEH). The objective of this study was to determine the influence of systolic blood pressure at extubation (e-SBP) on POSEH. @*Methods@#A total of 352 patients who underwent single-level decompression surgery including laminectomy and/or discectomy with BESS under the diagnosis of spinal stenosis and herniated nucleus pulposus between August 1, 2018, and June 30, 2021, were reviewed retrospectively. The patients were divided into two, a POSEH group and a normal group without POSEH (no neurological complication). The e-SBP, demographic factors, and the preoperative and intraoperative factors suspected to influence the POSEH were analyzed. The e-SBP was converted to a categorical variable by the threshold level that was decided by maximum area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Antiplatelet drugs (APDs) were taken in 21 patients (6.0%), discontinued in 24 patients (6.8%), and not taken in 307 patients (87.2%). Tranexamic acid (TXA) was used in 292 patients (83.0%) in the perioperative period. @*Results@#Of the 352 patients, 18 patients (5.1%) underwent revision surgery for the removal of POSEH. The POSEH and normal groups were homogenous in age, sex, diagnosis, operation segments, operation time, and lab findings that were related to blood clotting, whereas there were differences in e-SBP (163.7 ± 15.7 mmHg in POSEH group and 154.1 ± 18.3 mmHg in normal group), APD (4 takers, 2 stoppers, 12 non-takers in POSEH group and 16 takers, 22 stoppers, 296 non-takers in normal group), and TXA (12 use, 6 not use in POSEH group and 280 use, 54 not use in normal group) in single variable analysis. The highest AUC in the ROC curve analysis was 0.652 for 170 mmHg e-SBP (p < 0.05). There were 94 patients in the high e-SBP group (≥ 170 mmHg) and 258 patients in the low e-SBP group. In multivariable logistic regression analysis, only high e-SBP was a significant risk factor for POSEH (p = 0.013; odds ratio, 3.434). @*Conclusions@#High e-SBP (≥ 170 mmHg) can influence the development of POSEH in biportal endoscopic spine surgery.
ABSTRACT
Background@#Spontaneous intracranial hypotension occurs due to cerebrospinal fluid leakage from the spinal column, and orthostatic headache is the most common clinical presentation. Recent studies showed that bilateral greater occipital nerve blockade demonstrated clinical efficacy in relieving post-dural puncture headache after caesarean section. CaseA 40-year-old male who presented severe orthostatic headache was consulted to our pain clinic from neurology department. He initially felt a dull nature pain over the whole occipital area which then spread over the frontal and parietal areas. His headache was combined with nausea and vomiting. An epidural blood patch was delayed until final cisternography, and bilateral greater occipital nerve blockade using ultrasound guidance was performed instead. After the blockade, the previously existing headache around the occipital and parietal areas disappeared completely, but mild headache persisted around the frontal area. @*Conclusions@#Greater occipital nerve blockade could be a good therapeutic alternative to improve headache resulting from spontaneous intracranial hypotension.
ABSTRACT
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.
ABSTRACT
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 <60 mL/min/1.73 m2. @*Results@#At baseline, 1,729 (54.2%) patients had NAFLD, of whom 94 (5.4%) had advanced liver fibrosis. During the follow-up of 8.3±3.6 years, 472 (14.8%) patients developed incident CKD: 220 (15.1%) in the non-NAFLD group, 231 (14.1%) in the NAFLD without advanced fibrosis group and 28 (31.1%) in the NAFLD with advanced fibrosis group. There was no increased risk of incident CKD in the NAFLD group compared to the non-NAFLD group (P=0.435). However, among patients with NAFLD, advanced liver fibrosis was associated with an increased risk of CKD (adjusted hazard ratio, 1.75; 95% confidence interval, 1.15 to 2.66; P=0.009). @*Conclusion@#Advanced liver fibrosis in patients with NAFLD is independently associated with an increased risk of incident CKD in patients with T2DM.
ABSTRACT
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<0.01). @*Conclusion@#The elevation of u-NAG was independently associated with a higher degree of hepatic fibrosis in patients with T2DM. Considering the common metabolic milieu of renal and hepatic fibrosis in T2DM, the potential use of u-NAG as an effective urinary biomarker reflecting hepatic fibrosis in T2DM needs to be validated in the future.
ABSTRACT
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 Surveysdatabase 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 Cardiol-ogy/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<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023). @*Conclusions@#Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.
ABSTRACT
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.
ABSTRACT
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
Purpose@#To date, no study has compared the effects of adding sodium glucose cotransporter-2 (SGLT-2) inhibitors to the combination of metformin plus dipeptidyl peptidase-4 (DPP-4) inhibitors to the effects of adding other conventional anti-diabetic drugs (ADDs) to the dual therapy. We aimed to compare the effect of adding SGLT-2 inhibitors with that of adding sulfonylurea (SU) in type 2 diabetes (T2D) patients inadequately controlled with metformin plus DPP-4 inhibitors. @*Materials and Methods@#This study was designed to evaluate the non-inferiority of SGLT-2 inhibitor to SU as an add-on therapy to the dual combination of metformin plus DPP-4 inhibitors. A total of 292 T2D patients who started SU or SGLT-2 inhibitors as an add-on therapy to metformin plus DPP-4 inhibitors due to uncontrolled hyperglycemia, defined as glycated hemoglobin (HbA1c) ≥7%, were recruited. After propensity score matching, 90 pairs of patients remained, and 12-week changes in HbA1c levels were reviewed to assess glycemic effectiveness. Data from these patients were analyzed retrospectively. @*Results@#After 12 weeks of triple therapy, both groups showed significant changes in HbA1c levels, with a mean of -0.9% in each group. The inter-group difference was 0.01% [95% confidence interval (CI): -0.26–0.27], and the upper limit of the 95% CI was within the limit for non-inferiority (0.40%). There were no inter-group differences in the changes of liver enzyme levels and kidney function. @*Conclusion@#Adding SGLT-2 inhibitors is not inferior to adding SU as a third-line ADD to metformin plus DPP-4 inhibitor combination therapy.
ABSTRACT
Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.
Subject(s)
Animals , Mice , Antioxidants/pharmacology , Mitochondria , Pruritus/chemically induced , Reactive Oxygen Species/metabolism , TRPA1 Cation ChannelABSTRACT
Background@#There are no data on comparison between clopidogrel monotherapy and prolonged dual antiplatelet therapy (DAPT) in patients at high-risk undergoing percutaneous coronary intervention (PCI). @*Methods@#Of 2,082 consecutive patients undergoing PCI using second-generation drugeluting stent (DES), we studied 637 patients at high-risk either angiographically or clinically who received clopidogrel longer than 24 months and were event-free at 12 months after index PCI. Patients were divided into 2 groups: the clopidogrel monotherapy group and the prolonged DAPT group. The primary outcome was a composite of all-cause death, non-fatal myocardial infarction (MI), definite or probable stent thrombosis, or stroke between 12 months and 36 months after the index PCI. @*Results@#In propensity score-matched population (246 pairs), the cumulative rate of primary outcome was 4.5% in the clopidogrel monotherapy group and 4.9% in the prolonged DAPT group (hazard ratio, 1.21; 95% confidence interval, 0.54–2.75; P = 0.643). There was no significant difference in all-cause death, MI, stent thrombosis, stroke between the clopidogrel monotherapy group and the prolonged DAPT group. @*Conclusion@#Compared with prolonged DAPT, clopidogrel monotherapy showed similar long-term outcomes in patients at high-risk after second-generation DES implantation.
ABSTRACT
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 clinicalpractice.
ABSTRACT
Background@#Insulin resistance (IR) and inflammation are closely related to each other and share common pathophysiological and metabolic mechanisms. We aimed to investigate the combined effect of IR and inflammation on comorbidities of type 2 diabetes mellitus (T2DM). @*Methods@#A total 3,758 patients with T2DM were recruited through Huh’s Diabetes Center from January 2003 to June 2009. Insulin sensitivity was measured by a rate constant for plasma glucose disappearance (Kitt , %/min) using short insulin tolerance test. High sensitivity C-reactive protein (hs-CRP) was used as a surrogate for inflammation. @*Results@#Patients with the lowest tertile of Kitt (IR group) showed worse cardio-metabolic parameters while those with the highest tertile of hs-CRP levels had worse cardio-metabolic parameters. The prevalence of metabolic syndrome, fatty liver, albuminuria, and carotid atherosclerosis decreased with Kitt tertile, but increased with hs-CRP tertile. In multiple regression analysis, both Kitt and hs-CRP were independent risk factors for comorbidities of T2DM. In addition, they showed synergistic effects on these comorbidities. @*Conclusion@#Both IR and inflammation were significantly associated with comorbidities of T2DM in a dose dependent manner. In addition, the coexistence of IR and inflammation may synergistically contribute to increased comorbidities of T2DM.
ABSTRACT
Othematoma is a condition in which blood collects beneath the perichondral layer of the pinna. Recurrent auricular hematoma can be a challenging medical problem, with complications resulting in ear deformity, therefore, appropriate management is important. Improper treatment can result in a deformity known as ‘cauliflower ear’ or ‘wrestler’s ear.’ We report a case of othematoma that was inappropriately treated and present a review of current treatment options.
ABSTRACT
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@#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.