Insulin and glucagon secretions, and morphological change of pancreatic islets in OLETF rats, a model of type 2 diabetes mellitus.

This study was performed to observe the changes of glucose-related hormones and the morphological change including ultrastructure of the pancreatic islets in the male Otsuka Long-Evans Tokushima Fatty rat. Area under the curve (AUC) of glucose at the 30th (709 plus minus 73 mg.h/dL) and at the 40th week (746 plus minus 87 mg.h/ dL) of age were significantly higher than that at the 10th week (360 plus minus 25 mg.h/ dL). AUC of insulin of the 10th week was 2.4 plus minus 0.9 ng.h/mL, increased gradually to 10.8 plus minus 8.3 ng.h/mL at the 30th week, and decreased to 1.8 plus minus 1.2 ng.h/mL at the 40th week. The size of islet was increased at 20th week of age and the distribution of peripheral alpha cells and central beta cells at the 10th and 20th weeks was changed to a mixed pattern at the 40th week. On electron microscopic examination, beta cells at the 20th week showed many immature secretory granules, increased mitochondria, and hypertrophied Golgi complex and endoplasmic reticulum. At the 40th week, beta cell contained scanty intracellular organelles and secretory granules and apoptosis of acinar cell was observed. In conclusion, as diabetes progressed, increased secretion of insulin was accompanied by increases in size of islets and number of beta-cells in male OLETF rats showing obese type 2 diabetes. However, these compensatory changes could not overcome the requirement of insulin according to the continuous hyperglycemia after development of diabetes

국내 미기록인 흡혈성 산거머리 Haemadipsa rjukjuana Oka, 1910 보고

The terrestrial leeches from the peripheral island of the Korean Peninsula were identified as Haemadipsa rjukjuanaOka, 1910. The arhynchobdellid family Haemadipsidae and H. rjukjuana are newly added into the Korean leechfauna. This species is blood-feeding leech that attacks birds and medium or large sized mammals primarily,including human. The sequence of mitochondrial cytochrome c subunit I (COI), and the additional biology for thisspecies are presented. This is the first study of terrestrial blood-feeding leeches in Korea.OAIID:oai:osos.snu.ac.kr:snu2013-01/102/0000051105/10SEQ:10PERF_CD:SNU2013-01EVAL_ITEM_CD:102USER_ID:0000051105ADJUST_YN:NEMP_ID:A077262DEPT_CD:551FILENAME:haemadipsa rjukjuana (131204).pdfDEPT_NM:수의학과SCOPUS_YN:NCONFIRM:

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated

Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone

Increased Hepatic Insulin Action in Diet-Induced Obese Mice Following Inhibition of Glucosylceramide Synthase

Obesity is characterized by the accumulation of fat in the liver and other tissues, leading to insulin resistance. We have previously shown that a specific inhibitor of glucosylceramide synthase, which inhibits the initial step in the synthesis of glycosphingolipids (GSLs), improved glucose metabolism and decreased hepatic steatosis in both ob/ob and diet-induced obese (DIO) mice. Here we have determined in the DIO mouse model the efficacy of a related small molecule compound, Genz-112638, which is currently being evaluated clinically for the treatment of Gaucher disease, a lysosomal storage disorder.DIO mice were treated with the Genz-112638 for 12 to 16 weeks by daily oral gavage. Genz-112638 lowered HbA1c levels and increased glucose tolerance. Whole body adiposity was not affected in normal mice, but decreased in drug-treated obese mice. Drug treatment also significantly lowered liver triglyceride levels and reduced the development of hepatic steatosis. We performed hyperinsulinemic-euglycemic clamps on the DIO mice treated with Genz-112638 and showed that insulin-mediated suppression of hepatic glucose production increased significantly compared to the placebo treated mice, indicating a marked improvement in hepatic insulin sensitivity.These results indicate that GSL inhibition in obese mice primarily results in an increase in insulin action in the liver, and suggests that GSLs may have an important role in hepatic insulin resistance in conditions of obesity

Usability Analysis of Collision Avoidance System in Vehicle-to-Vehicle Communication Environment

Conventional intelligent vehicles have performance limitations owing to the short road and obstacle detection range of the installed sensors. In this study, to overcome this limitation, we tested the usability of a new conceptual autonomous emergency braking (AEB) system that employs vehicle-to-vehicle (V2V) communication technology in the existing AEB system. To this end, a radar sensor and a driving and communication environment constituting the AEB system were simulated; the simulation was then linked by applying vehicle dynamics and control logic. The simulation results show that the collision avoidance relaxation rate of V2V communication-based AEB system was reduced compared with that of existing vehicle-mounted-sensor-based system. Thus, a method that can lower the collision risk of the existing AEB system, which uses only a sensor cluster installed on the vehicle, is realized

Association between metabolic parameters and glomerular hyperfiltration in a representative Korean population without chronic kidney disease.

AimsTo investigate associations of glomerular hyperfiltration with other metabolic factors in a nationally representative dataset.MethodsWe analyzed cross-sectional data from 15,918 subjects with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 and urine albumin creation ratio (ACR) ResultsPrevalence of hyperfiltration was 5.2% and that among normal, prediabetic, and diabetic subjects was 4.9%, 5.6%, and 7.3%, respectively, after adjusting for age, sex, and body weight (p for trend = 0.008). In a multiple logistic regression analysis, hyperfiltration was associated with a body mass index ≥30 kg/m2 [odds ratio (OR) = 3.461, pConclusionsIn a general Korean population, both hyperfiltration and ACR were associated with similar metabolic parameters, and hyperfiltration correlated independently with a high ACR. Longitudinal studies are needed to further explore risks of hyperfiltration and microalbuminuria

Joint approach of diffusion- and perfusion-weighted MRI in intra-axial mass like lesions in clinical practice simulation.

Although advanced magnetic resonance imaging (MRI) techniques provide useful information for the differential diagnosis of intra-axial mass-like lesions, the specific diagnostic role of multimodal MRI over conventional magnetic resonance imaging (CMRI) alone in the differential diagnosis of mass-like lesions from a large heterogeneous cohort has not been studied. In this study, we aimed to determine the added value of a joint approach of diffusion-weighted imaging (DWI) and dynamic-susceptibility-contrast perfusion imaging (DSC-PWI) for diagnosis of intra-axial mass-like lesions, comparing them with CMRI alone. Furthermore, we performed these evaluations in a manner simulating clinical practice. Our institutional review board approved this retrospective study and waived the requirement for informed consent. A total of 1038 patients with intra-axial mass-like lesions were retrospectively recruited according to their histological and clinico-radiological diagnoses made between January 2005 and December 2014. All patients underwent CMRI, DWI and DSC-PWI. The diagnostic accuracy and confidence in diagnosing each type of intra-axial mass-like lesions, and for differentiating the intra-axial brain tumors from non-neoplastic lesions, were compared according to the MRI protocols. The disease-specific sensitivity of joint approach differed according to specific disease entities in diagnosing each disease category. Joint approach provided the best diagnostic accuracy for discriminating intra-axial brain tumors from non-neoplastic lesions, with high diagnostic accuracy (95.3-96.7%), specificity (82-84.0%), positive-predictive-value (97.0-97.3%), and negative-predictive-value (84.8-92.7%), with the reader's confidence values being significantly improved over those on CMRI alone (all p-values < 0.001). In conclusion, joint approach of DWI, DSC-PWI to CMRI helps to differentiate non-neoplastic lesions from intra-axial brain tumors, and improves diagnostic confidence compared with CMRI alone. The benefit from the combined imaging differs for each disease category; thus joint approach needs to be customized according to clinical suspicion

Additional file 1: Table S1. of Clinical implications of carotid artery intima media thickness assessment on cardiovascular risk stratification in hyperlipidemic Korean adults with diabetes: the ALTO study

Mean cIMT values that were used as cutoff values for determining subclinical atherosclerosis. Table S2. Correlation between 10-year cardiovascular risk and cIMT measures UKPDS Framingham Risk Score. Table S3. cIMT measures between UKPDS coronary heart disease risk groups by gender and age. Table S4. Univariate predictors of subclinical atherosclerosis. Table S5. Multivariate independent predictors of subclinical atherosclerosis. Table S6. Mean cIMT according to age and the status of statin use. Figure S1. Receiver operating characteristic curve analysis of conventional risk scores in predicting subclinical atherosclerosis (p = 0.189). (DOCX 787 kb