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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. [ABSTRACT FROM AUTHOR]

Background: Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigated the effect of exogenous DLK1 on muscular atrophy. Methods: We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into three groups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1. The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes. Results: Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreased expression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reduced expression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscle differentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophy through the myostatin pathway. Conclusion: DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrial biogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

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 FROM AUTHOR]

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 clinical practice. [ABSTRACT FROM AUTHOR]

Background: This study investigated the overall status of diabetes control and screening for diabetic microvascular complications in patients with type 2 diabetes mellitus attending primary care clinics in Korea. Methods: In this cross-sectional observational study, 191 primary care clinics were randomly selected across Korea from 2015 to 2016. In total, 3,227 subjects were enrolled in the study. Results: The patients followed at the primary care clinics were relatively young, with a mean age of 61.4±11.7 years, and had a relatively short duration of diabetes (mean duration, 7.6±6.5 years). Approximately 14% of subjects had diabetic microvascular complications. However, the patients treated at the primary care clinics had suboptimal control of hemoglobin A1c levels, blood pressure, and serum lipid levels, along with a metabolic target achievement rate of 5.9% according to the Korean Diabetes Association guidelines. The screening rates for diabetic nephropathy, retinopathy, and neuropathy within the past 12 months were 28.4%, 23.3%, and 13.3%, respectively. Conclusion: The overall status of diabetes management, including the frequency of screening for microvascular complications, was suboptimal in the primary care clinics. More efforts should be made and more resources need to be allocated for primary care physicians to promote adequate healthcare delivery, which would result in stricter diabetes control and improved management of diabetic complications. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemic crisis is a metabolic emergency associated with diabetes mellitus. However, accurate epidemiologic information on cases of hyperglycemic crisis in Korea remains scarce. We evaluated trends in hyperglycemic crisis hospitalizations and in- and out-of-hospital mortality in Korea. We also predicted future trends. Methods: We extracted claims data with hyperglycemic crisis as the principal diagnosis from the National Health Insurance Service database in Korea from January 2004 to December 2013. We investigated the numbers of claims with hyperglycemic crisis and identified trends in hyperglycemic crisis based on those claims data. We predicted future trends by statistical estimation. Results: The total annual number of claims of hyperglycemic crisis increased from 2,674 in 2004 to 5,540 in 2013. Statistical analysis revealed an increasing trend in hyperglycemic crisis hospitalizations (P for trend <0.01). In contrast, the hospitalization rate per 1,000 diabetes cases showed a decreasing trend (P for trend <0.01) during this period. The mortality rate per 1,000 diabetes cases also showed a decreasing trend (P for trend <0.0001). However, no distinct linear trend in the case-related fatality rate at <60 days over the last decade was observed. The predicted number of annual claims of hyperglycemic crisis will increase by 2030. Conclusion: The number of hyperglycemic crisis hospitalizations in Korea increased in the last decade, although the hospitalization rate per 1,000 diabetes cases and mortality rate decreased. Also, the predicted number of annual claims will increase in the future. Thus, it is necessary to establish long-term healthcare policies to prevent hyperglycemic crisis. [ABSTRACT FROM AUTHOR]

Background: A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS). Methods: A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <-5% or % BW <-2% plus body mass index (BMI) <20 kg/m2. Results: After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels. Conclusion: Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management. [ABSTRACT FROM AUTHOR]

Background: Although the beneficial effects of statin treatment in dyslipidemia and atherosclerosis have been well studied, there is limited information regarding the renal effects of statins in diabetic nephropathy. We aimed to investigate whether, and which, statins affected renal function in Asian patients with diabetes. Methods: We enrolled 484 patients with diabetes who received statin treatment for more than 12 months. We included patients treated with moderate-intensity dose statin treatment (atorvastatin 10 to 20 mg/day or rosuvastatin 5 to 10 mg/day). The primary outcome was a change in estimated glomerular filtration rate (eGFR) during the 12-month statin treatment, and rapid renal decline was defined as a >3% reduction in eGFR in a 1-year period. Results: In both statin treatment groups, patients showed improved serum lipid levels and significantly reduced eGFRs (from 80.3 to 78.8 mL/min/1.73 m2 for atorvastatin [P=0.012], from 79.1 to 76.1 mL/min/1.73 m2 for rosuvastatin [P=0.001]). A more rapid eGFR decline was observed in the rosuvastatin group than in the atorvastatin group (48.7% vs. 38.6%, P=0.029). Multiple logistic regression analyses demonstrated more rapid renal function loss in the rosuvastatin group than in the atorvastatin group after adjustment for other confounding factors (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.42). Conclusion: These results suggest that a moderate-intensity dose of atorvastatin has fewer detrimental effects on renal function than that of rosuvastatin. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the prevalence of obesity in Korean men with Klinefelter syndrome (KS) and the associated risk factors for obesity and hyperglycemia. Methods: Data were collected retrospectively from medical records from 11 university hospitals in Korea between 1994 and 2014. Subjects aged ≥18 years with newly diagnosed KS were enrolled. The following parameters were recorded at baseline before treatment: chief complaint, height, weight, fasting glucose level, lipid panel, blood pressure, testosterone, luteinizing hormone, folliclestimulating hormone, karyotyping patterns, and history of hypertension, diabetes, and dyslipidemia. Results: Data were analyzed from 376 of 544 initially enrolled patients. The rate of the 47 XXY chromosomal pattern was 94.1%. The prevalence of obesity (body mass index ≥25 kg/m2) in Korean men with KS was 42.6%. The testosterone level was an independent risk factor for obesity and hyperglycemia. Conclusion: Obesity is common in Korean men with KS. Hypogonadism in patients with KS was associated with obesity and hyperglycemia. [ABSTRACT FROM AUTHOR]

Background: Epidemiological data is useful to estimate the necessary manpower and resources used for disease control and prevention of prevalent chronic diseases. We aimed to evaluate the incidence of diabetes and identify its trends based on the claims data from the National Health Insurance Service database over the last decade. Methods: We extracted claims data on diabetes as the principal and first additional diagnoses of National Health Insurance from January 2003 to December 2012. We investigated the number of newly claimed subjects with diabetes codes, the number of claims and the demographic characteristics of this population. Results: Total numbers of claimed cases and populations with diabetes continuously increased from 1,377,319 in 2003 to 2,571,067 by 2012. However, the annual number of newly claimed diabetic subjects decreased in the last decade. The total number of new claim patients with diabetes codes decreased as 30.9% over 2005 to 2009. Since 2009, the incidence of new diabetes claim patients has not experienced significant change. The 9-year average incidence rate was 0.98% and 1.01% in men and women, respectively. The data showed an increasing proportion of new diabetic subjects of younger age (<60 years) combined with a sharply decreasing proportion of subjects of older age (⩾60 years). Conclusion: There were increasing numbers of newly claimed subjects with diabetes codes of younger age over the last 10 years. This increasing number of diabetic patients will require management throughout their life courses because Korea is rapidly becoming an aging society. [ABSTRACT FROM AUTHOR]

A clinical prediction model can be applied to several challenging clinical scenarios: screening high-risk individuals for asymptomatic disease, predicting future events such as disease or death, and assisting medical decision-making and health education. Despite the impact of clinical prediction models on practice, prediction modeling is a complex process requiring careful statistical analyses and sound clinical judgement. Although there is no definite consensus on the best methodology for model development and validation, a few recommendations and checklists have been proposed. In this review, we summarize five steps for developing and validating a clinical prediction model: preparation for establishing clinical prediction models; dataset selection; handling variables; model generation; and model evaluation and validation. We also review several studies that detail methods for developing clinical prediction models with comparable examples from real practice. After model development and vigorous validation in relevant settings, possibly with evaluation of utility/usability and fine-tuning, good models can be ready for the use in practice. We anticipate that this framework will revitalize the use of predictive or prognostic research in endocrinology, leading to active applications in real clinical practice. [ABSTRACT FROM AUTHOR]