Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

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.

Background: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. Methods: Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. Results: Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. Conclusion This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Background: The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. Methods: This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. Results: Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. Conclusion Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.

Background: The incidence of early-onset diabetes is increasing among young adults.However, there are limited data on the characteristics and management of young Korean adults with diabetes. This study assessed the clinical and demographic characteristics, health behaviors, and mental health among young Korean adults with diabetes mellitus. Methods: This cross-sectional study included young Korean adults with diabetes (n = 225) with an onset age of 20–39 years from four university hospitals. Demographic characteristics, management of diabetes, and mental health were assessed using a questionnaire survey. Results: Type 2 diabetes was the most common type (73.3%), and 13.8% of participants were classified as other types or unknown. Approximately, 64.7% of participants had a strong family history of diabetes, and 76% had treatment within three months of diagnosis.Approximately, 11.1% of participants had diabetic complications; 39.1% of participants received insulin injections, including oral anti-diabetic medications. Additionally, 30.4% were smokers, and only 28% had active physical activity; 26.5% of participants had >3 hours of screen time. One third of participants never had breakfast, and 60.5% went out to eat at least three times a week. Half of the participants showed moderate to severe stress perception, and 21.4% of patients had moderate to severe levels of depression based on the Korean version of Beck Depression Inventory score. Conclusion Early-onset diabetes was associated with a strong family history and early insulin treatment. Young adults with diabetes had poor health behaviors and frequent mental depression. These findings suggest the necessity of health policies for improving health behaviors and mental distress.

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. METHODS: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor β [TGF-β], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. RESULTS: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-β1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. CONCLUSION: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC.
Apoptosis* ; Blotting, Western ; Cadherins ; Caspase 3 ; Cell Survival ; Down-Regulation* ; Drug Resistance ; Drug Therapy ; Endothelial Growth Factors ; Flavonoids ; Humans ; Microscopy, Fluorescence ; Microtubules ; Neoplasm Metastasis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; Sirolimus ; Thyroid Carcinoma, Anaplastic* ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A

BACKGROUND/AIMS: Treatment for cholangitis without common bile duct (CBD) stones has not been established in patients with gallstones. We investigated the usefulness of endoscopic biliary drainage (EBD) without endoscopic sphincterotomy (EST) in patients diagnosed with gallstones and cholangitis without CBD stones by endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS). METHODS: EBD using 5F plastic stents without EST was performed prospectively in patients with gallstones and cholangitis if CBD stones were not diagnosed by ERCP and IDUS. After ERCP, all patients underwent laparoscopic cholecystectomy. The primary outcomes were clinical and technical success. The secondary outcomes were recurrence rate of biliary events and procedure-related adverse events. RESULTS: Among 187 patients with gallstones and cholangitis, 27 patients without CBD stones according to ERCP and IDUS received EBD using 5F plastic stents without EST. The stents were maintained in all patients until laparoscopic cholecystectomy, and recurrence of cholangitis was not observed. After cholecystectomy, the stents were removed spontaneously in 12 patients and endoscopically in 15 patients. Recurrence of CBD stones was not detected during the follow-up period (median, 421 days). CONCLUSIONS: EBD using 5F plastic stents without EST may be safe and effective for the management of cholangitis accompanied by gallstones in patients without CBD stones according to ERCP and IDUS.
Cholangiopancreatography, Endoscopic Retrograde ; Cholangitis* ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Common Bile Duct* ; Drainage* ; Follow-Up Studies ; Gallstones* ; Humans ; Plastics ; Prospective Studies ; Recurrence ; Sphincterotomy, Endoscopic ; Stents ; Ultrasonography*

Cases of pancreatic ductal adenocarcinoma with multiple masses accompanying underlying pancreatic diseases, such as intraductal papillary mucinous neoplasm, have been reported. However, synchronous invasion without underlying pancreatic disease is very rare. A 61-year-old female with abdominal discomfort and jaundice was admitted to our hospital. Abdominal computed tomography (CT) revealed cancer of the pancreatic head with direct invasion of the duodenal loop and common bile duct. However, positron emission tomography-CT showed an increased standardized uptake value (SUV) in the pancreatic head and tail. We performed endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for the histopathologic diagnosis of the pancreatic head and the evaluation of the increased SUV in the tail portion of the pancreas, as the characteristics of these lesions could affect the extent of surgery. As a result, pancreatic ductal adenocarcinomas were confirmed by both cytologic and histologic analyses. In addition, immunohistochemical analysis of the biopsy specimens was positive for carcinoembryonic antigen and p53 in both masses. The two masses were ultimately diagnosed as pancreatic ductal adenocarcinoma, stage IIB, based on EUS-FNB and imaging studies. In conclusion, the entire pancreas must be evaluated in a patient with a pancreatic mass to detect the rare but possible presence of synchronous pancreatic ductal adenocarcinoma. Additionally, EUS-FNB can provide pathologic confirmation in a single procedure.
Adenocarcinoma, Mucinous/pathology/*ultrasonography ; Carcinoma, Pancreatic Ductal/pathology/*ultrasonography ; *Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Middle Aged ; Neoplasms, Multiple Primary/pathology/*ultrasonography ; Pancreas/pathology ; Pancreatic Neoplasms/pathology/*ultrasonography