Urinary exosomal microRNA profiling in type 2 diabetes patients taking dipeptidyl peptidase-4 inhibitor compared with sulfonylurea

Background@#Dipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group). @*Methods@#This was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction. @*Results@#Twenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index. @*Conclusion@#There was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.

Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea

Background@#Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. @*Methods@#The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. @*Results@#The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. @*Conclusion@#The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts

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 clinicalpractice.

Non-Laboratory-Based Simple Screening Model for Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Developed Using Multi-Center Cohorts

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 clinicalpractice.

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.

A Noisy Carbohydrate Addiction / 임상당뇨병

Carbohydrates are a primary source of energy and a major component of the structure of living things-; there are many different kinds. As eating behavior is a part of life, it was usually not described in addiction. However, sometimes it seems aspects of addiction. This eating behavior can also appear with regard to other food. A bio-psycho-social model is required for complex analysis of addiction. When highly addictive agents are excluded, we can usually identify a key factor related to the vulnerability of the individual to addictive behavior. Considering that every source of happiness can potentially lead to addictive behaviors, we need to be cautious about the controlling. Not every carbohydrate can be connected with addictive behavior. Addictive behavior could be associated with a variety of ingredients other than carbohydrates. Until recently, sweet substances were thought to be the primary culprit behind addictive behavior. It is necessary to identify the food component or other factors associated with a specific craving. A multidimensional approach to the psychology of addictive behaviors might be more useful than opposing carbohydrate consumption in general.

Clinical Characteristics of Thyrotoxicosis Presented by Coronary Spasm / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Cardiovascular symptoms are integral and often the most predominant clinical presentation in patients with thyrotoxicosis. In patients with known or suspected coronary artery disease, myocardial ischemia and angina-like chest pain may be presented due to increase in cardiac output and cardiac contractility as a result of thyrotoxicosis. In addition, coronary spasm may result in angina-like chest pain in thyrotoxicosis patients without any fixed coronary artery stenosis. However, there are few reports about clinical characteristics of thyrotoxicosis associated with coronary artery spasm. MATERIALS AND METHODS: Coronary angiography, thyroid function test, and follow-up clinical data of patients were analyzed retrospectively. RESULTS: Twelve patients with coronary artery spasm were included over 4.5 years (male:female, 5:7). The mean age of patients was 53.3 years (range, 27 to 68), and female patients were younger than male patients (mean, 56.2 vs. 51.2 years). Only 4 patients (33%) presented typical thyrotoxic symptoms. The causes of thyrotoxicosis were Grave's disease (75%) and painless thyroiditis (25%). On coronary angiography, severe coronary spasm was observed by provocation in 6 patients, and total occlusion of right coronary artery and left circumflex artery with chest pain developed in 2 of 6 patients. After antithyroid treatment, all patients became free of chest pain. CONCLUSION: Severe coronary artery spasm can be associated with thyrotoxicosis. Thyroid function test might be a differential diagnostic test in patients with coronary artery spasm. It should be considered that thyrotoxicosis can be presented by coronary artery spasm without typical symptom of thyrotoxicosis.

Insulin Autoimmune Syndrome with Diabetic Ketoacidosis / 임상당뇨병

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, elevated insulin level and a high level of insulin autoantibodies without previous insulin exposure. Among the clinical manifestations of insulin autoimmune syndrome, diabetic ketoacidosis is extremely rare. A 72-year-old diabetic woman was hospitalized with diabetic ketoacidosis. She suffered repeated fasting hypoglycemia after treatment of the diabetic ketoacidosis. Here we describe this case of insulin autoimmune syndrome manifested as diabetic ketoacidosis followed by recurrent hypoglycemia with a review of the relevant literature.

Summary of the Update to the Diabetic Neuropathy Management Guidebook / 임상당뇨병

The Korean Diabetes Association (KDA) published the 3rd edition of the diabetic neuropathy management guidebook in 2010. This publication has been recognized as the definitive guide for the clinical management of diabetic neuropathy in the Korean medical system. In this report, we provide a modified summary of the 3rd edition of the diabetic neuropathy management guidebook. We hope this summary will serve as a helpful reference in the daily clinical practice of diabetes care.

DNA Methylation of RUNX3 in Papillary Thyroid Cancer

BACKGROUND/AIMS: The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. METHODS: We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). RESULTS: RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. CONCLUSIONS: We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

A Case of Agranulocytosis and Soft Tissue Abscess after Increasing Methimazole Dose in a Patient with Graves Disease under Long-term Mainternance Therapy / 대한갑상선학회지

Antithyroid drugs (ATD) has been widely used to treat Graves' disease. However agranulocytosis, a serious fatal complication of ATD treatment, occurs in about 0.5 percent. The symptoms may mimic viral infections (fever, sore throat), and the potentially life-threatening pyogenic infections can go unrecognized initially. The median duration of drug exposure before the onset of acute agranulocytosis is within 30 days in most cases. We report a case of agranulocytosis with secondary soft tissue infection and abscess occuring after increasing the dose of methimazole in a woman who had taken methimazole for more than 10 years. We administered broad-spectrum antibiotics and aspirated the soft tissue abscess. A review of the medical literature regarding agranulocytosis in the setting of ATDs is presented.

Effect of 17-beta Estradiol on Adipocyte Lipin-1 Expression in OLETF Rat

BACKGROUND: 17 beta-estradiol is known to play an important role in glucose homeostasis. Lipin-1 is a nuclear protein that is essential in adipocyte differentiation and it is considered to play a role in ectopic fat deposition and the redistribution of fat. The aim of this study was to evaluate the effect of 17 beta-estradiol on the lipin-1 expression in the adipocytes of OLETF rats, which is an animal model of diabetes. METHODS: The OLETF rats were divided into 3 groups, 1) the sham-operation group (SHAM) 2) the castrated group (CAST) and 2) the castrated and estradiol treatment group (EST), and all the rats were at 6 weeks of age. LETO rats were used as a control group (LETO). 0.1 mg of estradiol valerate was injected subcutaneously every 4 weeks in the rats of the EST group. The visceral and subcutaneous tissues were isolated to evaluate the lipin-1 protein expression. The lipin-1 expression was measured in human visceral and subcutaneous preadipocytes. RESULTS: Less body weight gain was observed in the EST group compared with that of the SHAM group. In addition, improvement in the glucose tolerance was observed in the EST group. The lipin-1 expression in visceral fat was decreased in the SHAM and CAST groups, but it was but recovered in the EST group. The lipin-1 expression in the subcutaneous fat was decreased in the SHAM, CAST, and EST groups. CONCLUSION: Long term estradiol treatment in OLETF rats reduces the body weight gain and improves the glucose tolerance. Estradiol enhances the lipin-1 protein expression in the visceral adipocytes, but not in the subcutaneous adipocytes.

Protective Effects of Lithospermic Acid B on Diabetic Nephropathy in OLETF Rats Comparing with Amlodipine and Losartan / 당뇨병

BACKGROUND: Lithospermic acid B (LAB), an active component isolated from Salvia miltiorrhizae, has been reported to have renoprotective effects in type 1 and type 2 diabetic animal models. We examined the effects of LAB on the prevention of diabetic nephropathy compared with amlodipine, a calcium channel blocker, and losartan, an angiotensin receptor blocker, in Otsuka Long-Evans-Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes. METHODS: LAB (20 mg/kg), amlodipine (10 mg/kg), or losartan (10 mg/kg) was given orally once daily to 10-week-old male OLETF rats for 28 weeks. RESULTS: None of LAB, losartan, and amlodipine exhibited effects on blood glucose levels. Treatment with amlodipine or losartan resulted in similar reductions in blood pressure; however, LAB was less effective in lowering blood pressure. Albuminuria was markedly suppressed by losartan and LAB, but not by amlodipine. LAB treatment decreased levels of renal lipid peroxidation, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta1 (TGF-beta1). CONCLUSION: These results suggest that LAB has beneficial effects on the diabetic nephropathy in OLETF rats by decreasing oxidative stress and inflammation as potent as losartan.

Blood Eosinophilia in Patients Undergoing Continous Ambulatory Peritoneal Dialysis / 대한신장학회잡지

PURPOSE: The prevalence of blood eosinophilia in patients who are maintained on regular hemodialysis has been well established. Blood eosinophilia in patients initiating peritoneal dialysis has been mentioned, but its prevalence and etiologic factors have not been well delineated. Therefore, we performed this retrospective study to find out prevalence and possible etiologic factors of blood eosinophilia in patients undergoing continuous ambulatory peritoneal dialysis. METHODS: Between May 2001 to May 2004, the patients who began continuous ambulatory peritoneal dialysis at one renal center were included in this study. Patients with allergic history or allergic reaction during observed period were excluded. The routine peripheral WBC counts of 47 patients were reviewed and possible predisposing factors of eosinophilia were investigated. RESULTS: Blood eosinophilia was observed in 17 of 47 patients (35% of all patients). In most patients with blood eosinophilia, the time in which the eosinophil count began to be rise was within 40 days, and duration of eosinophilia was variable (mean+/-SD;74+/-67 days). The mean of the peak eosinophil count was 750+/-257/mm3 (mean+/-SD). Possible predisposing factors included recent parenteral iron therapy, but not statistically significant (p=0.09). CONCLUSION: Our retrospective study showed that the eosinophil counts in patients with end stage renal disease on continuous ambulatory peritoneal dialysis were frequently elevated. Predisposing factors for this eosinophilia were not clear, suggesting that immunologic disturbance by uremia or dialysis itself might have influence on eosinophil homeostasis.

A Case of Video-Assisted Thoracoscopic Pneumonectomy for Unilateral Diffuse Pulmonary Arteriovenous Malformation / 결핵및호흡기질환

Pulmonary arteriovenous malformations (PAVMs) are abnormal direct communications between the pulmonary arteries and veins. PAVMs may occur as either an isolated abnormality or in association with hereditary hemorrhagic telangiectasia, also called Osler-Weber-Rendu disease. The topic of PAVM has recently been extensively reviewed, but little is known about the clinical characteristics and course of patients having a diffuse pattern of the disease. Herein, is reported a case of unilateral diffuse PAVM in an 18 year old female patient, who underwent a right pneumonectomy, under a video-assisted thoracic surgery (VATS) approach, as the diffuse small pulmonary arteriovenous malformation involved the whole right lung.

A Case of Toluene-induced Renal Tubular Acidosis Presented with Hypokalemic Paralysis

Toluene is known to cause a moderate degree of hypokalemia, myalgia, and even muscular weakness. We encountered the patient with acute hypokalemic paralysis in a chronic glue sniffer. A 32-year-old Korean male was taken to the emergency room with muscle weakness and somnolence. His serum chemistries showed severe hypokalemia and hyperchloremic metabolic acidosis. The urine toxicology screening showed excess levels of hippuric acid. His serum potassium level and metabolic acidosis were corrected after interruption of the offending agents and KCl & bicarbonate replacement. We report a case of severe hypokalemic muscular paralysis with renal tubular acidosis resulting from toluene inhalation.