Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study.

AIMS: To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. MATERIALS AND METHODS: This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. RESULTS: Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. CONCLUSION: Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

Association between first-step analgesic use and cancer in patients with diabetes.

OBJECTIVES: This study aimed to determine the effectiveness of analgesics in inhibiting cancer development in patients with diabetes based on a sample cohort supplied by the Korean National Health Insurance Service. MATERIALS AND METHODS: Regular users of analgesics included those using prescription analgesics ≥ 15 days per month at least 6 times over 2 years after the diagnosis of diabetes mellitus (baseline). The effectiveness of analgesics in patients with diabetes was evaluated using metformin adherence and three models: model 1 was adjusted for age and sex; model 2 was further adjusted for body mass index (BMI), exercise, cholesterol, hypertension, and Charlson comorbidity index (CCI); and model 3 was further adjusted for analgesics. RESULTS: Based on stringent extraction criteria, the sample had a cancer incidence of 4.6%. The hazard ratios of models 1 and 2 were 0.830 and 0.865, respectively. The adjusted hazard ratio for all variables, including acetaminophen and nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen, was 0.871 (model 3). CONCLUSION: Regular use of analgesics by patients with diabetes decreased their risk of subsequent cancer development in this large national cohort. Compared with participants who did not develop cancer, those with cancer were older and more likely to be male, did not exercise, have more comorbidities (as assessed by CCI), and did not use analgesics regularly.

Plasma and urinary extracellular vesicle microRNAs and their related pathways in diabetic kidney disease.

To explore extracellular vesicle microRNAs (EV miRNAs) and their target mRNAs in relation to diabetic kidney disease (DKD), we performed paired plasma and urinary EV small RNA sequencing (n = 18) in patients with type 2 diabetes and DKD (n = 5) and healthy subjects (n = 4) and metabolic network analyses using our own miRNA and public mRNA datasets. We found 13 common differentially expressed EV miRNAs in both fluids and 17 target mRNAs, including RRM2, NT5E, and UGDH. Because succinate dehydrogenase B was suggested to interact with proteins encoded by these three genes, we measured urinary succinate and adenosine in a validation study (n = 194). These two urinary metabolite concentrations were associated with DKD progression. In addition, renal expressions of NT5E and UGDH proteins were increased in db/db mice with DKD compared to control mice. In conclusion, we profiled DKD-related EV miRNAs in plasma and urine samples and found their relevant target pathways.

Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real-world study.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice. METHODS: A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60-89; G3ab, 30-59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30-300; A3, > 300 mg/g) were used to define CKD status. RESULTS: Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %). Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation. CONCLUSIONS: Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.

Urinary and Blood MicroRNA-126 and -770 are Potential Noninvasive Biomarker Candidates for Diabetic Nephropathy: a Meta-Analysis.

BACKGROUND/AIMS: Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN. METHODS: PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed. RESULTS: Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value < 0.0001) downregulated in blood from patients with diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy. CONCLUSIONS: Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies.

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects.

OBJECTIVE: The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. DESIGN: This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. PATIENTS: The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges. MEASUREMENTS: Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. RESULTS: There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. CONCLUSIONS: Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH.

Probucol in Albuminuric Type 2 Diabetes Mellitus Patients on Renin-Angiotensin System Blockade: A 16-Week, Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To determine the effect of probucol on urine albumin excretion in type 2 diabetes mellitus patients with albuminuria using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. APPROACH AND RESULTS: This was a 16-week, phase II, randomized, placebo-controlled, parallel-group study in type 2 diabetes mellitus patients with a urinary albumin/creatinine ratio of ≥300 mg/g using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, conducted in 17 tertiary referral hospitals. Eligible patients were randomized to probucol 250 mg/d (n=44), probucol 500 mg/d (n=41), and placebo (n=41) groups in a ratio of 1:1:1 after block randomization procedures, keeping the treatment assignment blinded to the investigators, patients, and study assistants. The primary end point was change in the geometric mean of urinary albumin/creatinine ratio from baseline to week 16 (ClinicalTrials.gov identifier NCT01726816). The study was started on November 8, 2012, and completed on March 24, 2014. The least squares mean change±SE from baseline in urinary albumin/creatinine ratio at week 16 was -7.2±639.5 mg/g in the probucol 250 mg/d group (n=43; P=0.2077 versus placebo group), 9.3±587.4 mg/g in the probucol 500 mg/d group (n=40; P=0.1975 versus placebo group), and 259.0±969.1 mg/g in the placebo group (n=41). Although the majority of subjects were on statins, probucol treatment significantly lowered total cholesterol and low-density lipoprotein cholesterol levels. QT prolongation occurred in one and two subjects in control and probucol 250 mg/d groups, respectively. CONCLUSIONS: Four months of probucol up to 500 mg/d failed to reduce urinary albumin excretion.

A randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes.

The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m(2), respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.

Differences in fear of failure and college adjustment by type of medical school entrance extrinsic motivation using a latent profile analysis.

PURPOSE: The decision to enroll in medical school is largely influenced by extrinsic motivation factors. It is necessary to explore the factors that affect pre-med students' motivation to enter medical school and their college adjustment, and to develop measures to help them adjust. METHODS: A total of 407 pre-med students were surveyed regarding their motivation to enter medical school, fear of failure, and college adjustment. We analyzed the latent profiles of extrinsic motivation factors using latent profile analysis. One-way analysis of variance was conducted to examine the differences in fear of failure and adaptation to university life according to the latent groups. RESULTS: After analyzing the latent profiles of entrance motivation, three latent profiles were selected. They were divided into high, medium, and low extrinsic motivation groups. Three profiles scored the highest on job security, followed by good grades and social status. Sophomores were more likely to be high extrinsic motivators than freshmen were. Fear of failure was high in the group with high extrinsic motivation, and adaptation to college life was highest in the group with low extrinsic motivation. CONCLUSION: Job security was the most important extrinsic motivator for entering medical school, and extrinsic entrance motivation influenced fear of failure and college adjustment. Given the high level of extrinsic motivation among medical students, it is meaningful to analyze the extrinsic motivation profile of entering medical students and how it affects failure motivation and college adjustment.

Analysis of the perceptions, competencies, and educational needs for global health among Korean medical students.

PURPOSE: The purpose of this study was to examine perceptions of global health education (GHE) among medical students and their involvement in global health activities and identify priorities of educational needs for developing GHE programs. METHODS: This study was cross-sectional and conducted through an online survey for medical students. The participants were students attending medical schools nationwide, and the final analysis target was 678. The survey developed questionnaires necessary for research purposes regarding global health-related experiences and perceptions, level of awareness of global health competencies (GHC), and needs assessments. The data were analyzed using the frequency analysis, chi-square test, independent t-test, Borich Needs Assessment Model, and the Locus for Focus Model. RESULTS: In total, 60.6% (411/678) agreed on the need for GHE, whereas 12.1% (82/678) agreed on the appropriateness of GHE in the current medical school curriculum, indicating a perception gap between the necessity and the status. At the current level of awareness of global health and GHC, we identified statistically significant differences according to gender, participation in global health activities, and GHE. In the analysis of the educational needs of GHC, all items of GHC had statistically significant differences between the importance level and the current level, and priorities were derived. The competency with the highest priority was domain A (Global Burden of Disease). CONCLUSION: We expect the findings of this study to be used in Korean medical education as fundamental data to prepare a hereafter research foundation for GHE and discuss systematic GHE based on GHC.

A Composite Blood Biomarker Including AKR1B10 and Cytokeratin 18 for Progressive Types of Nonalcoholic Fatty Liver Disease.

Background: We aimed to evaluate whether composite blood biomarkers including aldo-keto reductase family 1 member B10 (AKR1B10) and cytokeratin 18 (CK-18; a nonalcoholic steatohepatitis [NASH] marker) have clinically applicable performance for the diagnosis of NASH, advanced liver fibrosis, and high-risk NASH (NASH+significant fibrosis). Methods: A total of 116 subjects including healthy control subjects and patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD) were analyzed to assess composite blood-based and imaging-based biomarkers either singly or in combination. Results: A composite blood biomarker comprised of AKR1B10, CK-18, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) showed excellent performance for the diagnosis of, NASH, advanced fibrosis, and high-risk NASH, with area under the receiver operating characteristic curve values of 0.934 (95% confidence interval [CI], 0.888 to 0.981), 0.902 (95% CI, 0.832 to 0.971), and 0.918 (95% CI, 0.862 to 0.974), respectively. However, the performance of this blood composite biomarker was inferior to that various magnetic resonance (MR)-based composite biomarkers, such as proton density fat fraction/MR elastography- liver stiffness measurement (MRE-LSM)/ALT/AST for NASH, MRE-LSM+fibrosis-4 index for advanced fibrosis, and the known MR imaging-AST (MAST) score for high-risk NASH. Conclusion: Our blood composite biomarker can be useful to distinguish progressive forms of NAFLD as an initial noninvasive test when MR-based tools are not available.

Consensus on global health competencies for Korean medical students using a modified Delphi method.

PURPOSE: This study aimed to reach a consensus among experts on the global health competencies for medical students in Korea. METHODS: A global health competency model was developed to identify domains and competencies for medical education, and a three-round modified Delphi method was used to reach consensus among 21 experts on the essential global health competencies. The degree of convergence, degree of consensus, and content validity ratio of the model were used to reach a consensus. RESULTS: A list of 52 competencies in 12 domains were identified according to a literature review. In the first-round Delphi survey, the global health competencies were refined to 30 competencies in eight domains. In the second round, the competencies were reduced to 24. In the final round, consensus was reached among the expert panel members, and the competencies were finalized. The global health competency domains for medical students include global burden of disease (three items), globalization of health and healthcare (five items), determinants of health (two items), healthcare in low-resource settings (two items), global health governance (three items), health as a human right (four items), cultural diversity and health (three items), and participation in global health activities (two items). CONCLUSION: The group of experts in global health achieved a consensus that 24 global health competencies in eight domains were essential for undergraduate medical education in Korea. The domains and competencies identified herein can be used to develop an undergraduate medical education curriculum in global health.

Identification and characterization of C106R, a novel mutation in the DNA-binding domain of GCMB, in a family with autosomal-dominant hypoparathyroidism.

OVERVIEW: Glial cells missing B (GCMB) is a transcription factor that is expressed in the parathyroid hormone (PTH)-secreting cells of the parathyroid glands. Several mutations in GCMB have been reported to cause hypoparathyroidism (HP). We identified a family with two individuals in two generations (mother and son), who are affected by autosomal-dominant hypoparathyroidism (AD-HP). A novel heterozygous mutation in exon 2 of GCMB was identified in both affected individuals that changes cysteine at position 106 of the putative DNA-binding domain of GCMB to arginine (C106R). METHODS: We performed mutational analysis of the genes encoding GCMB, pre-pro PTH, GATA3 and CaSR using polymerase chain reaction (PCR)-amplified genomic DNA. The identified GCMB mutant was characterized by functional studies including nuclear localization, electrophoretic mobility shift assays (EMSA) and luciferase reporter assays, and homology modelling was performed to generate a three-dimensional structural model for the DNA-binding domain of GCMB to predict the structural consequences of the identified mutation. RESULTS: The C106R mutant of GCMB failed to interact with the DNA consensus recognition motif, as determined by EMSA. Furthermore, in comparison with wild-type GCMB, the C106R mutant demonstrated reduced transactivation in luciferase reporter assays; however, the mutant GCMB failed to reduce the activity of the wild-type protein. Consistent with the EMSA findings, homology modelling analysis suggested that replacement of cysteine 106 with arginine would interfere with DNA binding. CONCLUSIONS: We have identified a novel GCMB mutation that may explain AD-HP in our family. However, the exact mechanism by which this heterozygous mutation leads to the disease in the described family remains to be elucidated.

Association between nutrient intake and obesity in type 2 diabetic patients from the Korean National Diabetes Program: a cross-sectional study.

The aim of the study was to assess the association between usual dietary nutrient intake and obesity in Korean type 2 diabetic patients. We examined 2,832 type 2 diabetic patients from the Korean National Diabetes Program cohort who completed dietary assessment and clinical evaluation in this cross-sectional study. In men, higher dietary fiber intake was associated with a lower odds of being obese (P(trend) = 0.003) and in women, higher protein intake was associated with a lower odds of being obese (P(trend) = 0.03) after adjustment for age, diabetes duration, HbA1c, alcohol drinking, income, education level, and calorie intake. In men, higher fiber intake was associated with lower odds of obesity after further adjustment for diastolic blood pressure, physical activity, and possible confounding nutritional intake and medication. The multivariable adjusted odds ratio for the highest quintile of fiber intake was 0.37 (P(trend) < 0.001). In women, protein intake was not associated with obesity after further adjustment. In conclusion, higher intake of dietary fiber is associated with lower odds of being obese in type 2 diabetic men, suggesting a role for dietary fiber in the management and prevention of obesity in type 2 diabetes (ClinicalTrials.gov: NCT 01212198).

Association Between DPP4 Inhibitor Use and the Incidence of Cirrhosis, ESRD, and Some Cancers in Patients With Diabetes.

CONTEXT: There are relatively few data on noncardiovascular (non-CV) long-term clinical outcomes of dipeptidyl peptidase 4 inhibitor (DPP4i) treatment. OBJECTIVE: We aimed to evaluate some non-CV effects of DPP4is in patients with diabetes. METHODS: Based on data from the National Health Insurance Service database in Korea (2007-2018), we conducted 3 pairwise comparisons of metformin-combined antidiabetic therapies in adult patients with diabetes: DPP4is vs (1) all other oral antidiabetic agents, (2) sulfonylureas/glinides, and (3) thiazolidinediones (TZDs). Major outcomes were liver cirrhosis, end-stage renal disease (ESRD), and cancers in the liver, kidney, and pancreas. Adjusted hazard ratios (HRs) and 95% CIs for the outcomes were estimated using an adjusted Cox model. RESULTS: Of the 747 124 patients included, 628 217 had received DPP4i therapy for a mean duration of 33.8 ± 25.0 months. Compared with TZD therapy, DPP4i therapy was associated with higher adjusted HRs [95% CIs] for liver cirrhosis (1.267 [1.108-1.449]), ESRD (1.596 [1.139-2.236]), liver cancer (1.117 [1.011-1.235]), and pancreatic cancer (1.158 [1.040-1.290]). Furthermore, apart from liver cirrhosis, a higher risk of each of these outcomes was associated with DPP4i use than with non-DPP4i use. The higher adjusted HRs associated with DPP4i use further increased when patients with long-term exposure to DPP4is were analyzed. CONCLUSION: DPP4i therapy in patients with diabetes was associated with a higher risk of liver cirrhosis and cancer, ESRD, and pancreatic cancer than TZD therapy and, except for liver cirrhosis, the risk of these outcomes was greater with DPP4i treatment than with non-DPP4i treatment.

Magnetic Resonance-Based Assessments Better Capture Pathophysiologic Profiles and Progression in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Several noninvasive tools are available for the assessment of nonalcoholic fatty liver disease (NAFLD) including clinical and blood biomarkers, transient elastography (TE), and magnetic resonance imaging (MRI) techniques, such as proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE). In the present study, we aimed to evaluate whether magnetic resonance (MR)-based examinations better discriminate the pathophysiologic features and fibrosis progression in NAFLD than other noninvasive methods. METHODS: A total of 133 subjects (31 healthy volunteers and 102 patients with NAFLD) were subjected to clinical and noninvasive NAFLD evaluation, with additional liver biopsy in some patients (n=54). RESULTS: MRI-PDFF correlated far better with hepatic fat measured by MR spectroscopy (r=0.978, P<0.001) than with the TE controlled attenuation parameter (CAP) (r=0.727, P<0.001). In addition, MRI-PDFF showed stronger correlations with various pathophysiologic parameters for cellular injury, glucose and lipid metabolism, and inflammation, than the TE-CAP. The MRI-PDFF and TE-CAP cutoff levels associated with abnormal elevation of serum alanine aminotransferase were 9.9% and 270 dB/m, respectively. The MRE liver stiffness measurement (LSM) showed stronger correlations with liver enzymes, platelets, complement component 3, several clinical fibrosis scores, and the enhanced liver fibrosis (ELF) score than the TE-LSM. In an analysis of only biopsied patients, MRE performed better in discriminating advanced fibrosis with a cutoff value of 3.9 kPa than the TE (cutoff 8.1 kPa) and ELF test (cutoff 9.2 kPa). CONCLUSION: Our results suggest that MRI-based assessment of NAFLD is the best non-invasive tool that captures the histologic, pathophysiologic and metabolic features of the disease.

Body Fat Is Related to Sedentary Behavior and Light Physical Activity but Not to Moderate-Vigorous Physical Activity in Type 2 Diabetes Mellitus.

BACKGROUND: Sedentary behavior (SB) has emerged as a new risk factor for cardiovascular accidents. We investigated whether physical activity levels or SB were related to percent body fat (%BF) in type 2 diabetes mellitus (T2DM). METHODS: In this cross sectional study, we measured the duration of SB, light physical activity (LPA), moderate to vigorous physical activity (MVPA), total energy expenditure, and step counts using a wireless activity tracker (Fitbit HR; FB) for 7 days in free-living conditions, along with %BF using a bio impedance analyzer (Inbody; Biospace) in 120 smartphone users with T2DM. Subjects were divided into exercise (Exe, n=68) and non-exercise (nonExe, n=52) groups based on self-reports of whether the recommended exercises (30 min/day, 3 days/week for 3 months) were performed. SBt, LPAt, MVPAt were transformed from SB, LPA, MVPA for normally distributed variables. RESULTS: Participants were: female, 59.2%; age, 59.3±8.4 years; body mass index, 25.5±3.4 kg/m²; glycosylated hemoglobin (HbA1c), 7.6%±1.2%; %BF, 30.4%±7.1%. They performed SB for 15.7±3.7 hr/day, LPA for 4.4±1.7 hr/day, and MVPA for 0.9±0.8 hr/day. The %BF was related to SBt and LPAt, but not to MVPA after adjustments for age, gender, and HbA1c. VPA was significantly higher in the Exe group than in the nonExe group, but SB, LPA, and moderate physical activity were not different. Predicted %BF was 89.494 to 0.105 (age), -13.047 (gender), -0.507 (HbA1c), -7.655 (LPAt) (F[4, 64]=62.929, P<0.001), with an R² of 0.785 in multiple linear regression analysis. CONCLUSION: Reduced body fat in elderly diabetic patients might be associated with reduced inactivity and increased LPA.

The profiles of microRNAs from urinary extracellular vesicles (EVs) prepared by various isolation methods and their correlation with serum EV microRNAs.

AIMS: MicroRNAs (miRNAs) that circulate in biological fluids are frequently enclosed in extracellular vesicles (EVs). However, urinary EVs and their cargo miRNAs have not been systematically studied according to their EV isolation methods. METHODS: In type 2 diabetes mellitus persons with diabetic nephropathy (n = 4), we compared miRNA species in urine EVs prepared by ultracentrifugation (UC), qEV original size exclusion column (qEV), ExoQuick-TC Plus (ExoQuick), and ultrafiltration using Amicon Ultra centrifugal filter devices (Amicons) 10 K and 100 K. EV miRNAs were profiled by next-generation sequencing (NGS). Additionally, we evaluated the correlations of EV miRNA expression between the urine and serum samples isolated by UC. RESULTS: From each of 100 ml of urine, the UC method yielded the highest number of EV miRNA species (233 ± 37.3), with the ExoQuick yielded the lowest (103 ± 17.4). Urine EV miRNA profiles were highly correlated between UC, qEV, ExoQuick and Amicon 10 K methods. EV miRNA profiles between the urine and serum samples showed variable correlations between the patients (paired sample number = 3, r = 0.39-0.72). CONCLUSIONS: UC, qEV, ExoQuick, and Amicon 10 K are acceptable for urinary EV isolation to profile miRNAs. Urine- and serum-derived EV miRNA profiles have variable correlations depending on specific patients.

γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial.

BACKGROUND: This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). METHODS: This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). RESULTS: Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments. CONCLUSION: GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Medical education in Korea: the e-learning consortium.

This article reports the latest development in e-learning in Korean medical education. The Korean Consortium for e-Learning in Medical Education was formed for collaboration in providing quality online learning resources for medical schools around the nation. This e-learning strategy is aimed at improving the quality of medical education at the national level by providing students with equal access to quality learning resources and fostering students' self-directed learning and, in doing so, enhancing the effectiveness and efficiency of developing online learning resources by sharing necessary resources among the medical schools. The consortium also plans to share e-learning content with medical schools in other countries by engaging more medical schools in the consortium and also by sharing e-learning content developed by other institutions or consortiums. The consortium is also dedicated to the research and development of effective online learning strategies for medical education, including interactive virtual patient cases and other innovative pedagogies using Web 2.0 technologies.