Efficacy and Safety of Omega-3 Fatty Acids in Patients Treated with Statins for Residual Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

BACKGROUND: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia.METHODS: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and <500 mg/dL and LDL-C levels <110 mg/dL. Eligible subjects were randomized to ATOMEGA (OM3-FAs 4,000 mg plus atorvastatin calcium 20 mg) or atorvastatin 20 mg plus placebo groups. The primary efficacy endpoints were the percent changes in TG and non-HDL-C levels from baseline at the end of treatment.RESULTS: After 8 weeks of treatment, the percent changes from baseline in TG (−29.8% vs. 3.6%, P<0.001) and non-HDL-C (−10.1% vs. 4.9%, P<0.001) levels were significantly greater in the ATOMEGA group (n=97) than in the atorvastatin group (n=103). Moreover, the proportion of total subjects reaching TG target of <200 mg/dL in the ATOMEGA group was significantly higher than that in the atorvastatin group (62.9% vs. 22.3%, P<0.001). The incidence of adverse events did not differ between the two groups.CONCLUSION: The addition of OM3-FAs to atorvastatin improved TG and non-HDL-C levels to a significant extent compared to atorvastatin alone in subjects with residual hypertriglyceridemia.

Is There a Difference in Serum Vitamin D Levels and Bone Mineral Density According to Body Mass Index in Young Adult Women?

BACKGROUND: In the life cycle, bone mineral density (BMD) is the most optimal condition in the 20s. In Korea, vitamin D deficiency status is very serious in Korean women due to recent lack of activity, weight polarization, and inadequate nutritional intake. The purpose of this study was to compare serum vitamin D and BMD according to obesity status in Korean young adult women. METHODS: A total of 143 female college students participated in the research. Body fat and lean body status were analyzed using a body composition analyzer. Nutrient intakes of the subjects were assessed by 3-days food record method. The BMDs was measured by dual energy X-ray absorptiometry. The subjects were divided into normal weight group and obesity group on their body mass index. RESULTS: Obesity group showed significantly higher weight, body fat (%), and body fat (kg) than normal weight group and T-scores of lumbar-2 spines were significantly lower. Obesity group showed high triglyceride and low-density lipoprotein cholesterol levels and vitamin D levels were significantly lower. Physical fitness and activity status showed that sit and reach and sit up were significantly lower in obesity group. The intake of carbohydrates was higher in the obesity group than in the normal weight group, and the intake of vitamin C and vitamin D was significantly lower. Factors affecting serum vitamin D were analyzed as body fat (%), lumbar-2 T-score, triglyceride, and carbohydrate intake. CONCLUSIONS: Obese women need more effort to manage their serum vitamin D status and balanced nutrition to prevent bone loss.

Differential Diagnosis of Thyroid Follicular Neoplasm from Nodular Hyperplasia by Shear Wave Elastography

OBJECTIVE: More than 50% of diagnostic surgery in cytologically indeterminate thyroid nodules revealed benign nodules of which nodular hyperplasia (NH) accounted for about half. Preoperative exclusion of NH may decrease diagnostic surgery. We aimed to study the diagnostic performance of shear wave elastography (SWE) to differentiate follicular neoplasm (FN) from NH in follicular lesions of thyroid nodules. METHODS: We analyzed the data from 61 patients who underwent SWE before ultrasound-guided core-needle biopsy (CNB) from August 2016 to May 2018 and CNB results were FN (n=19) and NH (n=42). We analyzed the magnitude of elasticity index (EI) and patterns of high EI area (EI >36 kPa). The patterns of high EI area was classified as marginal pattern (high EI areas are restricted in the outer 1/3 of the nodule) and traversing pattern (high EI areas approaching further to the center of the nodule within inner 2/3 of the nodule). RESULTS: The E(Max), E(Mean), E(SD), and percent of high EI area were significantly lower in FN than NH (P<0.001). The diagnostic performance to predict FN showed sensitivity, specificity, and accuracy of 95%, 90%, and 92% by E(Max) <42.1 kPa, and of 95%, 79%, and 84% by E(Mean) <23.5 kPa, and of 89%, 93%, and 92% by marginal pattern of high EI area, respectively. CONCLUSION: Novel diagnostic criteria of E(Max) less than 42.1 kPa and marginal pattern of high EI area on SWE can predict FN with high diagnostic accuracy, waiving diagnostic surgery of NH in indeterminate cytology.

Utility of shear wave elastography to detect papillary thyroid carcinoma in thyroid nodules: efficacy of the standard deviation elasticity

BACKGROUND/AIMS@#The aim of this study was to address the role of the elasticity index as a possible predictive marker for detecting papillary thyroid carcinoma (PTC) and quantitatively assess shear wave elastography (SWE) as a tool for differentiating PTC from benign thyroid nodules.@*METHODS@#One hundred and nineteen patients with thyroid nodules undergoing SWE before ultrasound-guided fine needle aspiration and core needle biopsy were analyzed. The mean (E(Mean)), minimum (E(Min)), maximum (E(Max)), and standard deviation (E(SD)) of SWE elasticity indices were measured.@*RESULTS@#Among 105 nodules, 14 were PTC and 91 were benign. The E(Mean), E(Min), and E(Max) values were significantly higher in PTCs than benign nodules (E(Mean) 37.4 in PTC vs. 23.7 in benign nodules, p = 0.005; E(Min) 27.9 vs. 17.8, p = 0.034; E(Max) 46.7 vs. 31.5, p < 0.001). The E(Mean), E(Min), and E(Max) were significantly associated with PTC with diagnostic odds ratios varying from 6.74 to 9.91, high specificities (86.4%, 86.4%, and 88.1%, respectively), and positive likelihood ratios (4.21, 3.69, and 4.82, respectively). The E(SD) values were significantly higher in PTC than in benign nodules (6.3 vs. 2.6, p < 0.001). E(SD) had the highest specificity (96.6%) when applied with a cut-off value of 6.5 kPa. It had a positive likelihood ratio of 14.75 and a diagnostic odds ratio of 28.50.@*CONCLUSIONS@#The shear elasticity index of E(SD), with higher likelihood ratios for PTC, will probably identify nodules that have a high potential for malignancy. It may help to identify and select malignant nodules, while reducing unnecessary fine needle aspiration and core needle biopsies of benign nodules.

Association between Serum Cystatin C and Vascular Complications in Type 2 Diabetes Mellitus without Nephropathy

BACKGROUND: Recent studies have correlated serum cystatin C (CysC) with vascular complications, but few studies have investigated this correlation in diabetes patients without nephropathy. This study aimed to evaluate if higher serum CysC levels increase the risk for vascular complications in type 2 diabetes mellitus patients with normal renal function or mild renal impairment. METHODS: A total of 806 consecutive patients with type 2 diabetes mellitus who were admitted to the diabetes center of Soonchunhyang University Hospital for blood glucose control were retrospectively reviewed. Patients with nephropathy were excluded. Subjects were categorized into quartiles of serum CysC levels (Q1, ≤0.65 mg/L; Q2, 0.66 to 0.79 mg/L; Q3, 0.80 to 0.94 mg/L; and Q4, ≥0.95 mg/L). RESULTS: The proportion of patients with diabetic retinopathy (DR) (P for trend < 0.001), coronary heart disease (CHD) (P for trend < 0.001), and stroke (P for trend < 0.001) increased across the serum CysC quartiles. After adjustment for confounding factors, the highest serum CysC level remained a significant risk factor for DR (odds ratio [OR], 1.929; 95% confidence interval [CI], 1.007 to 4.144; P=0.040). Compared with Q1, a significant positive association was observed between serum CysC and CHD in Q2 (OR, 7.321; 95% CI, 1.114 to 48.114; P=0.012), Q3 (OR, 6.027; 95% CI, 0.952 to 38.161; P=0.020), and Q4 (OR, 8.122; 95% CI, 1.258 to 52.453; P=0.007). No associations were observed between CysC and stroke after additional adjustment for confounding variables. CONCLUSION: Serum CysC levels are independently associated with DR and CHD, suggesting that CysC may be useful for identifying type 2 diabetes mellitus patients without nephropathy who are at high risk for vascular complications.

Association between Sarcopenia, Sarcopenic Obesity, and Chronic Disease in Korean Elderly

BACKGROUND: It is a very important social issue for Korea to have a healthy old age as an aged society. Aging causes a lot of physical changes, especially sarcopenia. Sarcopenia is defined as a persistent decrease in skeletal muscle and muscle strength. Sarcopenic obesity is a phenomenon in which fat is replaced instead of muscle. The purpose of this study was to examine the prevalence of sarcopenia and sarcopenic obesity in Korean elderly and to analyze the relationship with chronic disease. METHODS: Data from the 2008 to 2011 the Korea National Health and Nutrition Survey were used. A total of 3,492 patients were classified into 3 groups (non-sarcopenia, sarcopenia, sarcopenic obesity), and general, anthropometry, health behavior, nutrient intake and chronic disease status were compared by the statistical analysis. RESULTS: The rate of moderate exercise was significantly lower in the sarcopenia and sarcopenic-obesity group than in the non-sarcopenia group (P=0.007). The sarcopenic obesity group had significantly higher energy (P=0.005), protein (P=0.046) and fat (P=0.001) intake than the sarcopenic group. The sarcopenic-obesity group had the highest ratio of diabetes (P=0.023) and dyslipidemia (P=0.004) in the 3 groups. Compared with the non-sarcopenia group, in the sarcopenia and sarcopenic obesity groups, the odds ratios (ORs) of diabetes was increased by 1.24 and 2.16 while the ORs of dyslipidemia was increased by 1.12 and 1.50, respectively. CONCLUSIONS: Regular exercise and adequate nutrient intake (energy, protein and fat) are essential for the prevention of sarcopenia in Korean elderly, and management of chronic disease in sarcopenic obesity elderly is important.

Linking resistin, inflammation, and cardiometabolic diseases

Adipose tissue secretes a variety of bioactive substances that are associated with chronic inflammation, insulin resistance, and an increased risk of type 2 diabetes mellitus. While resistin was first known as an adipocyte-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents, it is predominantly expressed and secreted by macrophages in humans. Epidemiological and genetic studies indicate that increased resistin levels are associated with the development of insulin resistance, diabetes, and cardiovascular disease. Resistin also appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and the formation of foam cells. Thus, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with cardiovascular disease and heart failure. Furthermore, recent evidence suggests that resistin is associated with atherogenic dyslipidemia and hypertension. The present review will focus on the role of human resistin in the pathogeneses of inflammation and obesity-related diseases.

Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects

BACKGROUND: Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort. METHODS: A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders. RESULTS: Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders. CONCLUSION: Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.

Connecting Myokines and Metabolism

Skeletal muscle is the largest organ of the body in non-obese individuals and is now considered to be an endocrine organ. Hormones (myokines) secreted by skeletal muscle mediate communications between muscle and liver, adipose tissue, brain, and other organs. Myokines affect muscle mass and myofiber switching, and have profound effects on glucose and lipid metabolism and inflammation, thus contributing to energy homeostasis and the pathogenesis of obesity, diabetes, and other diseases. In this review, we summarize recent findings on the biology of myokines and provide an assessment of their potential as therapeutic targets.

Relationship between Decrease in Serum Sodium Level and Bone Mineral Density in Osteoporotic Fracture Patients

BACKGROUND: Recently, it has been suggested that decrease in serum sodium level is associated with osteoporosis. However, no study in Korea has reported the association of decrease in serum sodium level with osteoporosis. In this study, we investigated the relationship between the decrease in serum sodium level and severity of osteoporotic fracture in patients. METHODS: We enrolled 290 subjects who were admitted and operated at Soonchunhyang University Hospital due to major fractures. For the control group, we enrolled 1,027 subjects who visited a health promotion center. We carried a 1:1 matching with age and sex from the case group. RESULTS: In a total of 164 age- and sex-matched subjects, serum sodium level was significantly lower in the fracture group than in the non-fracture group (P=0.001). Serum sodium level was significantly lower in the severe osteoporosis group than that in the non-severe osteoporosis group (P=0.002). Old age and decrease in serum sodium level were independent risk factors of osteoporosis (odds ratio [OR]=1.088, P=0.008, confidence interval [CI]=[1.022-1.157]; OR= 0.840, P=0.037, CI=0.713-0.989). CONCLUSIONS: Serum sodium level was significantly lower in the fracture group than that in the non-fracture group and in the severe osteoporosis group than that in the non-severe osteoporosis group. Based on our results, the decrease in serum sodium level could be an independent risk factor for osteoporosis.

Severe Hypoglycemia and Cardiovascular Disease in Type 2 Diabetes

No abstract available.

Consideration of Discrepancy between Needle-Washout Thyroglobulin and Serum Thyroglobulin of Recurrent Papillary Thyroid Cancer

Although the prognosis of papillary thyroid cancer (PTC) is extremely good, locoregional recurrences after initial treatment occur. Thyroglobulin (Tg) is a reliable tumor marker to detect recurrence or persistence of PTC. However, occasionally serum Tg may miss the detection of a recurrence. We report a 54-year-old female presented with hoarseness due to cervical recurrence without concomitant elevation of serum Tg and anti-Tg antibody, in contrast to extremely increased needle-washout Tg, who had undergone a total thyroidectomy and radioiodine ablation as initial therapies for PTC. Several factors causing such discrepancy between needle-washout Tg and serum Tg can be suggested including site of recurrence, volume of tumor, interference by some kind of plasma antibodies other than anti-Tg antibody, and any conformational defect of Tg protein. Among them, the most convincing explanation is that any conformational defect of Tg may lead to impaired secretion of Tg to blood. We suggest that more studies are needed to find the cause for potential mechanisms involved in PTC recurrences without increased serum Tg.

Methimazole-Induced Acute Cholestatic Hepatitis in a Patient with History of Simvastatin-Induced Liver Injury

Methimazole and prophylthiouracil are commonly prescribed for patients with hyperthyroidism. The serious side effect of toxic hepatitis caused by these two drugs is well known. According to recent Korean and American management guidelines for hyperthyroidism, mehimazole is recommended as the first-choice antithyroid drug for the treatment of hyperthyroidism. Toxic hepatitis rarely occurs in methimazole users. We report a rare case of a 52-year-old female with toxic hepatitis after methimazole use that had past medical history of simvastatin induced liver injury.

Resistin in Rodents and Humans

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

Letter: Predicting Mortality of Critically Ill Patients by Blood Glucose Levels (Diabetes Metab J 2013;37:385-90)

No abstract available.

Two Cases of Hemichorea Associated with Nonketotic Hyperglycemia in Type 2 Diabetes Mellitus Patient

Hemichorea-hemiballism is a rare complication of nonketotic hyperglycemia in type 2 diabetes mellitus (T2DM). It can be complicated in long-standing type 1 diabetes mellitus or T2DM, and has been described as a presenting symptom of new-onset diabetes. Rapid correction of diabetic ketoacidosis may also cause the delayed hemichorea. Although hyperglycemic hemiballism rarely causes generalized chorea due to bilateral basal ganglia involvement, patients typically present with hemichorea developing over days to months in the setting of elevated serum glucose. On T1-weighted brain magnetic resonance imaging and computed tomography scan a high signal intensity lesion at the basal ganglia is characteristic. After the correction of hyperglycemia, the movements generally disappear within hours, but atypical cases with delayed onset after the resolution of hyperglycemia, unremitting severe movements, and late recurrence are also reported. We report two cases of female T2DM patients who presented with hemichorea. One patient presented with hemichorea in nonketotic hyperglycemia, and the other with delayed onset hemichorea after the resolution of hyperglycemia.

Metformin and Cancer in Type 2 Diabetes

No abstract available.

Endoscopic comparison of alendronate alone and the enteric-coated alendronate with calcitriol combination in postmenopausal Korean females

BACKGROUND/AIMS: This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 microg) combined drug (Maxmarvil, Yuyu Co.). METHODS: The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 +/- 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. RESULTS: Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. CONCLUSIONS: The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.

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.

Relationship between Serum Cystatin C and Arterial Stiffness in Type 2 Diabetes Patients with Normal Renal Function

OBJECTIVE: Several studies showed that increased arterial stiffness is an independent risk factor for cardiovascular disease. Pulse wave velocity (PWV) is known as a marker for large vessel stiffness. Recent studies show that serum cystatin C is associated with PWV and may predict future cardiovascular events, even in subjects with normal renal function. However, there have been few studies for the relationship between cystatin C and arterial stiffness in patients with type 2 diabetes (T2DM). In this study, we investigated the relationship between serum cystatin C and branchial-ankle PWV in T2DM patients with normal renal function. METHODS: Patients with urinary albumin/creatinine ratio (ACR) higher than 300 microg albumin/mg creatinine, estimated glomerular filtration rate (eGFR) less than 60 mL/min were excluded. A total of 88 patients (47 male/41 female; age, 59+/-2 years; ACR, 33+/-5 microg/mg) were included. Doppler-derived aortic PWV and serum cystatin C were measured. RESULTS: Cystatin C is significantly related to age (r=0.51, P<0.001), hemoglobin A1c (r=-0.23, P<0.05), high density lipoprotein-cholesterol (r=-0.22, P<0.05), apoprotein A (r=-0.22, P<0.05), and eGFR (r=-0.56, P<0.001). Aortic PWV is significantly associated with age (r=0.29, P<0.01), cystatin C (r=0.33, P<0.005), and eGFR (r=-0.24, P<0.05). In multiple regression analysis, there is significant association between aortic PWV and serum cystatin C levels. CONCLUSION: Serum cystatin C is significantly associated with arterial stiffness in T2DM patients with normal renal function. Our results suggest that cystatin C could be a marker for early atherosclerosis in T2DM patients.