BACKGROUND:Patients with type 2 diabetes mellitus (T2DM) prone to acute diabetic complications are at high risk for emergency department (ED) visits, which often precede hospitalization and mortality. Identifying these high-risk phenotypes before deterioration is critical for preventative care. We developed machine learning (ML) models using large-scale, real-world electronic medical records, including prescription data, to predict the possibility of ED visits in patients with T2DM and support proactive interventions in primary care settings. METHODS:We analyzed the electronic health record data of five independent institutions, creating a comprehensive dataset of 220,720 patients. The data included dynamic clinical parameters such as vital signs, laboratory results, and prescription histories. The cohort was randomly split into a training set (n = 176,576) and a test set (n = 44,144). The primary outcome was the first ED visit. We developed multiple ML models using an automated ML framework and optimized them using hyperparameter tuning of the training set. Model performances were evaluated using the area under the receiver operating characteristic (AUROC) curve, and feature importance was analyzed using SHAP values to ensure interpretability. RESULTS:Among the screened population, 49,770 (22.6%) experienced at least one ED visit, distributed proportionally across the training and test datasets. The CatBoost model demonstrated superior predictive performance, achieving an AUROC of 0.87 (95% CI, 0.862-0.871) on the test dataset. The model identified modifiable risk factors as key predictors; Diastolic blood pressure was the most significant variable, followed by serum creatinine and systolic blood pressure. CONCLUSIONS:This ML-based predictive model can accurately identify high-risk patients with T2DM who are likely to visit the ED based on readily available clinical variables. By enabling healthcare providers to shift from reactive treatment to proactive risk management, it has the potential to reduce the burden of ED visits due to acute complications in T2DM.

PURPOSE:Chronic cough (CC), defined as a cough lasting more than 8 weeks, significantly impairs the health-related quality of life (HRQoL). Despite its prevalence, the relative disease burden of CC compared with that of other chronic diseases remains underexplored. This study aimed to evaluate and compare the HRQoL of patients with CC to those with rheumatoid arthritis (RA), diabetes mellitus (DM), chronic kidney disease (CKD) on hemodialysis (HD) and healthy controls. METHODS:This multicenter observational study compared HRQoL of 203 patients with CC to 152 with chronic disease (50 with RA, 53 with DM on insulin, 49 with CKD on HD) and 41 healthy controls. Participants completed the Leicester cough questionnaire and the short-form 36 (SF-36) to assess disease-specific and generic HRQoL, respectively. RESULTS:Patients with CC demonstrated significantly lower SF-36 scores compared to healthy controls (65.9 ± 18.9 vs. 81.5 ± 10.1, P < 0.001), with scores similar to those of patients with RA (65.2 ± 21.0) and DM (67.8 ± 17.4). Patients with moderate-to-severe CC experienced HRQoL impairments similar to patients with CKD on HD, especially in mental health domains. Patients with CC had the most pronounced impairments in vitality, role-physical, and social functioning compared to healthy controls. CONCLUSIONS:CC imposes a substantial burden comparable to or exceeding that of other chronic diseases. The mental health impairment in patients with moderate-to-severe CC emphasizes the psychological impact of CC. Therefore, further longitudinal research is required to explore the impact of tailored interventions on HRQoL outcomes.

Background : Beverage consumption patterns in Korea have shifted in response to rapid lifestyle changes, including the growth of cafe culture and increased access to convenience foods. This study examined trends in major beverage consumption among Korean young adults. Methods : Beverage consumption trends were analyzed using data from 7,681 participants aged 19-29 years from the Korea National Health and Nutrition Examination Survey (2010-2021). Dietary assessment methods differed by survey cycle: a simple food frequency questionnaire (FFQ) in 2010-2011, a semi-quantitative FFQ in 2012-2016, and beverage-specific questions in 2019-2021. Beverages included milk, yogurt, soda, coffee, and fruit juice. Weekly consumption frequency, consumption volume, and estimated sugar intake were analyzed by sex. Results : Beverage consumption patterns showed distinct temporal changes. The frequency of dairy product intake declined significantly (5.2 to 3.2 times/week; P<0.0001), mainly because of reduced milk consumption. Yogurt intake initially increased and then declined, particularly among females. In contrast, the overall frequency of sugar-sweetened beverage (SSB) intake remained stable, although coffee intake frequency decreased and soda and fruit juice intake increased slightly. Total SSB volume increased from 1.9 to 2.8 L per week (P<0.0001). The absolute increase was slightly greater in males (899.5 mL/week vs. 761.6 mL/week), whereas the relative increase in soda intake was greater in females (93% vs. 61%). Correspondingly, weekly sugar intake from SSBs rose sharply (122.7 to 177.6 g/week, P<0.0001), whereas sugar intake from dairy products did not change significantly. Conclusion : Among Korean young adults, dairy consumption has declined, whereas SSB intake and related sugar exposure have increased markedly, with notable sex differences in beverage consumption patterns.

Background Type 2 diabetes mellitus (T2DM) is a significant risk factor for hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease; however, surveillance strategies for patients with T2DM, especially without cirrhosis, are inadequate. This study examined whether the fatty liver index (FLI) and its dynamic changes can effectively identify patients with T2DM at increased risk for HCC. Methods Data from 92,761 individuals with T2DM aged 40 to 79 who underwent two health screenings (2012 to 2015) were analyzed. The FLI, calculated using waist circumference, body mass index, triglycerides, and gamma-glutamyl transferase, was used to stratify patients by baseline FLI and FLI changes between screenings. HCC cases were identified via International Classification of Diseases codes and reimbursement records (2016 to 2020). Results Patients with baseline FLI of 30 to 59.9 had a 1.90-fold higher risk (P<0.01) and those with FLI ≥60 had a 2.94-fold higher risk (P<0.01) of developing HCC compared to those with FLI <30. An increase in FLI from <30 to ≥30 resulted in a 2.10-fold higher risk of HCC (P<0.01), while a reduction in FLI from ≥30 to <30 led to a 0.64-fold lower risk (P=0.03). Protective benefits of FLI reduction took approximately 3 years to manifest. Conclusion Baseline and dynamic monitoring of FLI effectively identified HCC risk in T2DM patients with non-cirrhotic livers, supporting early detection and intervention.

Background Nonalcoholic fatty liver disease, a progressive condition caused by the accumulation of fat in the liver, begins with simple steatosis and can potentially progress to metabolic dysfunction-associated steatohepatitis (MASH) in the presence of inflammation and fibrosis, ultimately leading to cirrhosis or hepatocellular carcinoma. Increasing evidence indicates that sodiumglucose cotransporter 2 (SGLT2) inhibitors effectively alleviate MASH in mouse models. However, there is a lack of research on the effects of enavogliflozin on liver disease. In the present study, we investigated the effects of SGLT2 inhibitors on MASH induced by a high-fat, high-cholesterol (HFHC) diet in mice. Methods Male C57BL/6 mice were fed a normal chow diet, HFHC diet, or HFHC diet with enavogliflozin for 12 weeks. LX-2 and HepG2 cells were treated with enavogliflozin in the presence of various pathological stimuli. Results The HFHC diet induced excessive hepatic lipid accumulation, inflammation, and severe fibrosis. Administration of enavogliflozin not only ameliorated hepatic steatosis and fibrotic conditions but also suppressed the production of inflammatory cytokines. Positive outcomes were also observed in in vitro experiments, where enavogliflozin demonstrated the ability to impede the activation of hepatic stellate cells and alleviate lipid accumulation in hepatocytes. The potential pathway through which enavogliflozin attenuated liver fibrosis development may be associated with the transforming growth factor β1/Smad signaling pathway. Conclusion Our results suggest that enavogliflozin is effective in a mouse model of MASH by attenuating hepatic steatosis, suppressing inflammation, and improving liver fibrosis.

ABSTRACTBackgroundHepatic stellate cells (HSCs) activation is the principal event in the development of liver fibrosis in which succinate-GPR91 signaling has recently been shown to be a contributor. Moreover, endoplasmic reticulum (ER) stress has been reported to involve in HSC activation, but its association with succinate in pathogenesis of liver fibrosis remains scarce. In this study, we investigated the role of gemigliptin, an antidiabetic DDP-4 inhibitor, in the succinate-induced ER stress and activation of HSCs.MethodsLX-2 cells, the immortalized human HSCs, were treated with succinate and gemigliptin. For animal experiments, C57BL/6N mice were divided into 3 groups: control diet, high-fat high-cholesterol (HFHC) diet, and HFHC diet mixed with gemigliptin.ResultsSuccinate significantly induced HSC activation and increased expression of inflammatory markers and the increase in the migration of HSCs. The treatment of succinate also caused ER dilation and activated the unfolded protein response (UPR) signaling as PERK, eIF2alpha, Bip, suggesting increasing ER stress in HSCs. All responses of HSCs to succinate were attenuated with the co-treatment of gemigliptin. Moreover, the exposure of HSCs to tunicamycin, an inducer of ER stress, promoted the expression of α-SMA, proliferation and migration of HSCs. In vivo, the level of fibrotic and ER stress markers was increased in mice fed with HFHC diet and the administration of gemigliptin improved these changes in HFHC-induced mice.ConclusionThis study showed the involvement of ER stress in the activation of succinate-induced LX-2 HSCs and gemigliptin significantly reduced ER stress in HSC activation. Therefore, gemigliptin may become an anti-fibrotic agent and targeting to succinate and ER stress may be a promising therapeutic in the management of liver fibrosis.

BACKGRUOUND:Lactate, traditionally considered a metabolic byproduct, is increasingly recognized as a signaling molecule involved in metabolic regulation. Its role in hepatic steatosis, particularly through G-protein-coupled receptor 81 (GPR81)-mediated pathways, remains underexplored. METHODS:We investigated the effects of lactate on hepatic lipid metabolism using in vitro alpha mouse liver 12 (AML12) cells, zebrafish, and two diet-induced nonalcoholic fatty liver disease (NAFLD) mouse models. Lipid accumulation, gene/protein expression, and 5' adenosine monophosphate-activated protein kinase (AMPK) signaling were assessed under lactate exposure, GPR81 knockdown, monocarboxylate transporter 1 (MCT1) inhibition, and AMPK activation conditions. RESULTS:Lactate treatment in hepatocytes increased de novo lipogenesis and fatty acid uptake while suppressing fatty acid oxidation and AMPK phosphorylation. These effects were reversed by GPR81 knockdown but not by MCT1 inhibition, suggesting a GPR81-dependent mechanism. AMPK activation with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) reduced lactate-induced lipid accumulation. In zebrafish, 10 mM lactate treatment for 24 hours significantly increased hepatic lipid content. In mice fed high-fat diet (HFD) or high-fat high-cholesterol (HFHC) diets for 12 weeks, hepatic lactate levels and GPR81 expression were elevated. Interestingly, p-AMPK expression decreased in HFD livers but increased in the HFHC group, indicating dietspecific regulation. CONCLUSION:Our findings demonstrate that lactate promotes hepatic steatosis primarily via the GPR81-AMPK signaling axis. GPR81 activation enhances lipogenesis and lipid uptake, independent of MCT1-mediated transport. These results position GPR81 as a promising therapeutic target for NAFLD.

Purpose: Self-management of diabetes is a significant challenge. This study aimed to assess diabetes self-care activities and barriers among Korean young adults with diabetes mellitus. Materials and Methods: This study recruited 209 Korean adults with diabetes, with an onset age of 20-39 years, from four university hospitals. Demographic characteristics and the Summary of Diabetes Self-Care Activities (SDSCA) measure and Diabetes Self-Care Barriers Assessment Scale for Older Adults (DSCB-OA) scores were assessed using questionnaires.Results: The average age of study participants was 32.9 +/- 6.1 years. Their self-care activities, including adherence to recommended diabetes medication (5.6 +/- 2.4) and number of diabetes pills (5.5 +/- 2.3) in the SDSCA measure, were the most well-performed activities among all domains. Responses to inspection of the inside of shoes in the foot care activity (0.8 +/- 1.5) and specific exercise sessions in the exercise activity (1.6 +/- 1.9) reflected poor levels of compliance. According to the DSCB-OA questionnaire, the mean diabetes self-care barrier of DSCB-OA was 20.6 +/- 5.0 of total score 45. The greater perceived barriers to self-care on the DSCB-OA were having difficulty exercising regularly (1.9 +/- 0.7) and eating three meals and snacks leading to weight gain (1.9 +/- 0.8).Conclusion: Young adults with early-onset diabetes showed a greater barrier to regular exercise and poor compliance with foot care and blood sugar testing. Healthcare providers must strengthen their relationship with young adults with diabetes to provide more education and guidelines for lifestyle modification focused on exercise and to promote higher compliance with diabetic self-care activities for improving clinical outcomes.

BACKGRUOUND:Liver fibrosis is a common outcome of chronic liver disease and is primarily driven by hepatic stellate cell (HSC) activation. Irisin, a myokine released during physical exercise, is beneficial for metabolic disorders and mitochondrial dysfunction. This study aimed to explore the effects of irisin on liver fibrosis in HSCs, a bile duct ligation (BDL) mouse model, and the associated mitochondrial dysfunction. METHODS:In vitro experiments utilized LX-2 cells, a human HSC line, stimulated with transforming growth factor-β1 (TGF-β1), a major regulator of HSC fibrosis, with or without irisin. Mitochondrial function was assessed using mitochondrial fission markers, transmission electron microscopy, mitochondrial membrane potential, and adenosine triphosphate (ATP) production. In vivo, liver fibrosis was induced in mice via BDL, followed by daily intraperitoneal injections of irisin (100 μg/kg/day) for 10 days. RESULTS:In vitro, irisin mitigated HSC activation and reduced reactive oxygen species associated with the TGF-β1/Smad signaling pathway. Irisin restored TGF-β1-induced increases in fission markers (Fis1, p-DRP1) and reversed the decreased expression of TFAM and SIRT3. Additionally, irisin restored mitochondrial membrane potential and ATP production lowered by TGF-β1 treatment. In vivo, irisin ameliorated the elevated liver-to-body weight ratio induced by BDL and alleviated liver fibrosis, as evidenced by Masson's trichrome staining. Irisin also improved mitochondrial dysfunction induced by BDL surgery. CONCLUSION:Irisin effectively attenuated HSC activation, ameliorated liver fibrosis in BDL mice, and improved associated mitochondrial dysfunction. These findings highlight the therapeutic potential of irisin for the treatment of liver fibrosis.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BACKGROUND:Chronic urticaria (CU) is a common chronic inflammatory disease, but the burden on quality of life (QOL) has been underestimated. OBJECTIVE:To compare QOL among patients with CU and those with other chronic diseases. METHODS:Adult patients who visited a referral hospital for CU were enrolled. Patients completed self-reported questionnaires including clinical characteristics of chronic urticaria and the short form 36 health survey. As a comparative group, patients with rheumatoid arthritis, patients with diabetes treated with insulin, patients on maintenance hemodialysis, and healthy controls were enrolled and completed the short form 36 health survey. RESULTS:In all, 119 patients with CU were enrolled and their short form 36 scores were not significantly different from those of healthy controls. However, patients with CU with poor responses to treatment showed impaired QOL to a degree similar to that of patients with rheumatoid arthritis or insulin-treated diabetes. The patients with CU showed various clinical characteristics with respect to treatment response, accompanying symptoms, and aggravating factors. Among these factors, pain at the urticarial lesion and symptom aggravation during exercise and after the consumption of certain foods were related with lower QOL. CONCLUSIONS:Patients with CU with an incomplete response to treatment had significantly low QOL, comparable to that of patients with rheumatoid arthritis or insulin-treated diabetes. To minimize this effect, clinicians should aim to control symptoms and aggravating factors.

Background: Hepatic stellate cells (HSCs) are the major cells which play a pivotal role in liver fibrosis. During injury, extracellular stimulators can induce HSCs transdifferentiated into active form. Phloretin showed its ability to protect the liver from injury, so in this research we would like to investigate the effect of phloretin on succinate-induced HSCs activation in vitro and liver fibrosis in vivo study.Methods: In in vitro, succinate was used to induce HSCs activation, and then the effect of phloretin on activated HSCs was examined. In in vivo, succinate was used to generated liver fibrosis in mouse and phloretin co-treated to check its protection on the liver.Results: Phloretin can reduce the increase of fibrogenic markers and inhibits the proliferation, migration, and contraction caused by succinate in in vitro experiments. Moreover, an upregulation of proteins associated with aerobic glycolysis occurred during the acti-vation of HSCs, which was attenuated by phloretin treatment. In in vivo experiments, intraperitoneal injection of phloretin decreased expression of fibrotic and glycolytic markers in the livers of mice with sodium succinate diet-induced liver fibrosis. These results suggest that aerobic glycolysis plays critical role in activation of HSCs and succinate can induce liver fibrosis in mice, whereas phloretin has therapeutic potential for treating hepatic fibrosis.Conclusion: Intraperitoneal injection of phloretin attenuated succinate-induced hepatic fibrosis and alleviates the succinate-induced HSCs activation.

Chronic urticaria (CU) is a common problem with a high disease burden that has a significant negative impact on quality of life. Many patients are undertreated, and awareness of management strategies is low among clinicians. The present study aimed to improve understanding of CU from the patients' perspective, including the disease burden and current healthcare system use. Adult patients who presented to our referral hospital for CU treatment completed self-report questionnaires about demographics, clinical characteristics of CU, the impact of CU on daily life, unmet needs, and the history of medical service usage. This self-report survey included 127 participants (females, 57.0%; mean age, 42.0 ± 13.6 years; mean CU duration, 1.8 ± 3.4 years); 51.6% reported frequent discomfort with CU in daily life, including 44.1% of those who reported a good response to medication. More than half of the respondents reported a depressed mood and anxiety. Although 46.4% of the respondents reported that urticaria completely disappeared while on medication, only 10% were satisfied with the CU management provided by primary care hospitals. The principal cause of dissatisfaction was that they did not know the cause of CU (68.4% of patients). In total, 55% of the patients visited 2 or more hospitals before presenting to our referral hospital and 6.3% had tried folk remedies. In conclusion, most patients report that CU is not adequately controlled. Therefore, in addition to appropriate medication, information on the cause of CU, long-term treatment plan, medication safety, and expected prognosis is required to meet patients' needs.

Exercise is an effective intervention to ameliorate metabolic diseases including obesity and insulin resistance, but the mechanisms involved in the metabolic amelioration have not yet been fully elucidated. This study aimed to determine whether AMPK–SIRT1–PGC-1α–FNDC5/Irisin-UCP1 expression is activated and whether metabolic dysfunction is ameliorated by chronic voluntary wheel running (VWR) in high-fat diet (HFD) induced obese mice. C57BL6J mice were randomly assigned into three groups at the age of 7 weeks for 10 weeks: normal chow diet (CON) group, HFD group, and HFD + VWR group. Chronic VWR ameliorates metabolic parameters and leads to increases in the expression of PGC-1α in the gastrocnemius muscle in HFD-induced obese mice. In contrast, the expression of AMPKα, SIRT1, and FNDC5, or circulating irisin levels did not lead to alteration. Improvement of metabolic health was partly mediated via PGC-1α expression by chronic VWR, but not FNDC5/Irisin pathway in HFD-induced obese mice.

Glucocorticoids (GCs) are steroid hormones produced in the adrenal cortex under the control of circadian rhythms and stress [1]. Since their discovery in the 1940s, GCs have been success-fully used as a mainstay of therapy to treat a wide range of chronic inflammatory diseases and autoimmune diseases and used as an immunosuppressive therapy following organ trans-plantation. However, long-term GC treatment is associated with diverse complications, such as infections, osteoporosis, cardiovascular disease, cancer

The comparative effectiveness of oral hypoglycemic agents on glycemic control and chronic complications in clinical practice is unknown in Korea. This study aimed to compare glycemic control and the incidence of hypoglycemia and chronic complications among adult patients with type 2 diabetes prescribed metformin, dipeptidyl peptidase-4 inhibitors (DPP4I), and sulfonylurea (SU) as monotherapy or dual combination therapy. We retrospectively analyzed propensity-matched cohort data from 3 national university hospitals in Korea. All electronic health records were transformed into a unified Observational Medical Outcomes Partnership Common Data Model and analyzed using ATLAS, an open-source analytical tool, and R software. Glycemic control was assessed as the first observation of a reduction in glycosylated hemoglobin (HbA1c) level below 7% after prescription of the drug. Differences in the incidence of chronic complications were compared based on the first observation of each complication. Glycemic control and chronic complications were evaluated in patients who maintained the same prescription for at least 3 and 12 months, respectively. Patients who received metformin had lower hazard of reaching HbA1c levels below 7% as compared with those who received SU, and had higher hazard compared with those who received DPP4I (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.98; and HR, 1.68; 95% CI, 1.42-1.99, respectively). The incidence of hypoglycemia was significantly higher in the SU group than in the metformin and DPP4I groups (metformin vs SU; HR, 0.30; 95% CI, 0.21-0.43; SU vs DPP4I; HR, 4.42; 95% CI, 2.35-8.31). Metformin + DPP4I had similar hazard of reaching HbA1c levels below 7% compared with metformin + SU (HR, 1.19; 95% CI, 0.99-1.43) and the incidence of hypoglycemia was significantly lower in the metformin + DPP4I group (HR 0.13; 95% CI 0.05-0.30). There was no significant difference in the analysis of the occurrence of chronic complications. SU followed by metformin was effective, and both drugs showed an increased hazard of reaching HbA1c levels below 7% compared with DPP4I. Metformin + DPP4I is comparatively effective for HbA1c level reduction below 7% compared with metformin + SU. Hypoglycemia was high in the SU-containing therapy.