RESUMO
AIMS: This study was designed to investigate the association between pancreatic fat content (PFC) and insulin secretory capacity as well as glucose tolerance in Korean adults. MATERIALS: A total of 39 participants (mean age 49.9 years, 53% males) without a previous history of diabetes, or those previously diagnosed as having diabetes but with less than 10 years of disease duration and no medication history were included. They were stratified according to the results of the oral glucose tolerance test (OGTT): normal glucose tolerance, prediabetes, and diabetes. METHODS: All participants underwent the proton magnetic resonance spectroscopy (1 H-MRS) to assess PFC. Insulin sensitivity and ß-cell function were measured by the frequently sampled intravenous glucose tolerance tests (FSIVGTT) and OGTT-derived indices. RESULTS: As glucose tolerance deteriorated, parameters such as Stumvoll index, oral glucose insulin sensitivity index, homeostatic model assessment (HOMA)-ß, insulinogenic index and oral disposition index from the OGTT, and acute insulin response to glucose (AIR) and disposition index (DI) from the FSIVGTT were decreased. PFC increased with deterioration in glucose tolerance (NGT: 12.0%, prediabetes: 23.7%, and diabetes: 31.9%). Correlation analysis indicated that glucose levels at 60 and 120 min during the OGTT were positively correlated with PFC. Also, there was a significant negative correlation between PFC and DI as well as AIR derived from the FSIVGTT. CONCLUSIONS: PFC evaluated by 1 H-MRS in Korean adults was higher in those diagnosed with diabetes than those with normal glucose tolerance status. PFC also showed a significant negative correlation with indices reflecting beta cell function.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Adulto , Glicemia , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/diagnóstico , República da Coreia/epidemiologiaRESUMO
BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited syndrome that concurrently involves various endocrine glands. We report a rare case of MEN1 in a 43-year-old man whose first manifestation was an asymptomatic mediastinal mass. CASE PRESENTATION: A 13-cm-sized mediastinal mass was diagnosed as an atypical thymic carcinoid by computed tomography and percutaneous needle biopsy. In addition, hypercalcemia from a left inferior parathyroid hyperplasia, and a non-functioning gastric neuroendocrine tumor seen on esophagogastroduodenoscopy were found. Therefore, the patient was clinically diagnosed with MEN1 syndrome, and underwent surgical resection of thymic carcinoid tumor after pre-operative concurrent chemoradiation therapy to decrease tumor size and volume. Parathyroid lesion and gastric neuroendocrine tumor were also removed. Finally, a MEN1 gene mutation was observed in the patient and his 7-year-old son. CONCLUSION: Despite its rare occurrence, thymic carcinoid tumor should be considered as a MEN1-associated tumor and necessitates screening of other endocrine glands. Thymic carcinoid tumor carries a poor prognosis in patients with MEN1, and thus it needs to be carefully monitored even after radical excision.
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Doenças Assintomáticas , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico por imagem , Timoma/diagnóstico por imagem , Neoplasias do Timo/diagnóstico por imagem , Adulto , Humanos , Masculino , Neoplasias do Mediastino/complicações , Neoplasia Endócrina Múltipla Tipo 1/complicações , Timoma/complicações , Neoplasias do Timo/complicaçõesRESUMO
BACKGROUND: Risk of fragility fractures increases in patients with diabetes mellitus, independent of bone mineral density. In the present study, the effects of advanced glycation end products (AGEs) on differentiation and function of osteoblasts and osteoclasts were investigated. METHODS: AGEs and 25 mM glucose were administered to marrow-derived macrophages and MCT3T3-E1 cells. The effects of AGEs on osteoclast differentiation was investigated using tartrate-resistant acid phosphatase (TRAP) assay. The effects of AGEs on osteoblast differentiation was investigated using alkaline phosphatase (ALP) activity and bone nodule formation assays. Expression of osteoclast-specific and osteoblast-specific genes and effects on cell signaling pathways associated with cell differentiation were analyzed using reverse transcription polymerase chain reaction and western blotting. RESULTS: AGEs significantly decreased TRAP-positive multinucleated cell formation in receptor activator of nuclear factor-κB ligand-induced marrow-derived macrophages in a dose-dependent manner. AGEs suppressed the expression of osteoclast-specific genes, JNK, p38, AKT, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 1 in marrow-derived macrophages. AGEs decreased ALP activity and showed a tendency to decrease bone nodule formation in MC3T3-E1 cells. AGEs suppressed the expression of osteoblast-specific genes, lysyl hydroxylase and lysyl oxidase in MC3T3-E1 cells. CONCLUSION: AGEs suppressed differentiation and function of osteoclasts and osteoblasts, and collagen cross-linking activity. It suggests that AGE may induce bone fragility through low bone turnover and deterioration of bone quality.
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Diferenciação Celular/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Animais , Células da Medula Óssea/citologia , Linhagem Celular , Glucose/farmacologia , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/farmacologia , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/metabolismoRESUMO
Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.
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Adesão à Medicação , Osteoporose Pós-Menopausa/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida , Conservadores da Densidade Óssea/uso terapêutico , Estudos Transversais , Difosfonatos/uso terapêutico , Feminino , Humanos , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , República da Coreia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Activation of endoplasmic reticulum (ER) stress is involved in the development of nonalcoholic fatty liver disease. Glucagon-like peptide-1 (GLP-1) has been reported to reduce hepatic steatosis, but the underlying mechanism has not been fully elucidated. Here, we investigated whether exendin-4 (EX-4), a GLP-1 receptor analogue, improves hepatic steatosis through ER stress reduction. Furthermore, we explored which ER stress pathway is involved in this process, with a focus on the protein kinase RNA-like ER kinase (PERK)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway. EX-4 treatment reduced hepatic lipid accumulation by suppressing the expression of lipogenic genes and restoring the expression of ß-oxidation genes in palmitate-treated HepG2 cells and high fat diet (HFD)-fed mice. In addition, EX-4 treatment suppressed hepatic ER stress activation in HFD-fed mice and tunicamycin-treated mice. In particular, EX-4 treatment restored HFD- and tunicamycin-induced Nrf2 nuclear translocation to control levels. Inhibition of Nrf2 by siRNA enhanced phosphorylation of PERK and eukaryotic translation initiation factor 2α (eIF2α), as well as other substrates of the PERK pathway. Nrf2 knockdown also inhibited the protective effects of EX-4 against lipid accumulation, ER stress activation, and cell death in palmitate-treated HepG2 cells. EX-4 treatment prevents hepatic steatosis and improves cell survival by regulating hepatic lipid metabolism and reducing ER stress activation, and Nrf2 plays an essential role in the protective effect of GLP-1 on hepatic steatosis.
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Estresse do Retículo Endoplasmático/efeitos dos fármacos , Exenatida/metabolismo , Fígado Gorduroso/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Fígado/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Células Hep G2 , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
AIMS: This study aims to compare the preventive effect of low- or moderate-statin with ezetimibe combination therapy and high-intensity statin monotherapy on cardiovascular disease (CVD) and all-cause death in a real-world setting. METHODS AND RESULTS: Using the Korean National Health Insurance Service datasets, two cohorts comparing high-intensity statin monotherapy with low- or moderate-intensity statin and ezetimibe combination were constructed by 1:1 propensity score matching procedure. Primary outcome was a composite of myocardial infarction (MI), stroke, and all-cause death. Secondary outcome was an individual event. The study population was followed from baseline until the date of events, or the last health check-ups, whichever came first. Compared to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination significantly reduced the risk of composite outcome [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.77-0.92, P < 0.001] as well as individual MI (HR 0.81, 95% CI 0.71-0.94, P = 0.005) and stroke (HR 0.78, 95% CI 0.65-0.93, P = 0.005), but not all-cause death. Low-intensity statin with ezetimibe also significantly reduced the risk of the composite outcomes (HR 0.80, 95% CI 0.66-0.97, P = 0.024) compared to high-intensity statin monotherapy, but the risk of individual outcome did not differ between two groups. Statin and ezetimibe combination demonstrated consistent effect across various subgroups. CONCLUSION: Among people without pre-existing CVD, moderate-intensity statin with ezetimibe combination was superior to high-intensity statin monotherapy in preventing composite outcomes as well as each of MI and stroke. In contrast, low-intensity statin with ezetimibe combination reduced the risk of composite but not individual outcomes.
We compared the preventive effect of low- or moderate-statin with ezetimibe combination and high-intensity statin monotherapy on cardiovascular disease and all-cause death. Low- or moderate-intensity statin with ezetimibe is beneficial for reducing a composite of myocardial infarction (MI), stroke, and all-cause death. Moderate-intensity statin with ezetimibe reduced 19% of MI and 22% of stroke, compared with high-intensity statin. Statin with ezetimibe combination might be attractive bypass for primary prevention, beyond an alternative to high-intensity statin.
Assuntos
Doenças Cardiovasculares , Causas de Morte , Quimioterapia Combinada , Ezetimiba , Inibidores de Hidroximetilglutaril-CoA Redutases , Prevenção Primária , Pontuação de Propensão , Humanos , Masculino , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Feminino , Ezetimiba/uso terapêutico , Ezetimiba/administração & dosagem , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/mortalidade , Idoso , Resultado do Tratamento , Anticolesterolemiantes/uso terapêutico , Anticolesterolemiantes/administração & dosagem , Fatores de Tempo , Estudos Retrospectivos , Fatores de Risco , Medição de Risco , Bases de Dados Factuais , Dislipidemias/tratamento farmacológico , Dislipidemias/mortalidade , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Dislipidemias/sangueRESUMO
CONTEXT: Low-density lipoprotein cholesterol (LDL-C)-lowering therapy is considerably important in preventing cardiovascular disease (CVD) among patients with diabetes. Studies comparing CVD, stroke, and mortality outcomes of low- or moderate-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy in patients with diabetes remain lacking. OBJECTIVE: This study compared the primary prevention effect of myocardial infarction (MI), stroke, and all-cause death between combination therapy of low- or moderate-intensity statins and ezetimibe and high-intensity statin monotherapy in patients with diabetes using the Korean National Health Insurance claims database. METHODS: Patients aged ≥20 years with type 2 diabetes and dyslipidemia were enrolled. The combination therapy of low- or moderate-intensity statin and ezetimibe was compared with high-intensity statin monotherapy after a propensity score-matched analysis. The incidence of composite outcomes consisting of MI, stroke, and all-cause death and each component were analyzed. RESULTS: In moderate-intensity statin therapy with ezetimibe combination therapy, LDL-C (74 ± 37.9â mg/dL vs 80.8 ± 38.8â mg/dL, P < .001) and the incidence of composite outcomes were lower (hazard ratio 0.85, 95% CI 0.74-0.98) than those in high-intensity statin monotherapy. Meanwhile, no significant difference was observed in the LDL-C levels and composite outcomes between low-intensity statins with ezetimibe combination therapy and high-intensity statin monotherapy. CONCLUSION: Adding ezetimibe to a moderate-intensity statin in patients with type 2 diabetes has a greater LDL-C-lowering effect and greater primary prevention of composite outcomes than that of high-intensity statin monotherapy.
Assuntos
Anticolesterolemiantes , Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Ezetimiba , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Ezetimiba/uso terapêutico , Ezetimiba/administração & dosagem , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/uso terapêutico , Resultado do Tratamento , República da Coreia/epidemiologia , LDL-Colesterol/sangue , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Adulto , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Dislipidemias/sangue , Estudos Retrospectivos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidadeRESUMO
Optimal vitamin D concentrations for bone health have not been determined in the Korean population. The aim of this study was to define serum 25-hydroxyvitamin D (25[OH]D) concentrations that indicate insufficiency among older Korean adults as measured by serum intact parathyroid hormone (iPTH) concentrations and bone mineral density (BMD). We analyzed data from the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-3), which was conducted in Korea in 2009. We enrolled 1,451 men and 1,870 women aged 49 years and above. After adjusting for variables that could potentially affect serum 25(OH)D concentrations, we found that serum iPTH concentrations began to increase at serum 25(OH)D concentrations below 12.1 ng/mL (30.2 nmol/L). In addition, total-femur BMD increased until serum 25(OH)D concentrations dropped below 20.4 ng/mL (50.9 nmol/L); no significant changes were observed thereafter. Assuming that serum 25(OH)D concentrations below 12.1 and 20.4 ng/mL represent vitamin D insufficiency, the prevalences of vitamin D insufficiency were 8.7 and 50.4 % in men and 17.9 and 66.3 % in women, respectively. Serum 25(OH)D cutoff values of 12.1 ng/mL (OR = 1.26) and 20.4 ng/mL (OR = 1.54) were associated with osteoporosis (P < 0.01); osteoporosis was not associated with a 25(OH)D cutoff value of 30 ng/mL (75.0 nmol/L). In conclusion, serum 25(OH)D concentrations of 20 ng/mL might be sufficient for bone health in older Korean adults.
Assuntos
Osso e Ossos/fisiologia , Vitamina D/análogos & derivados , Idoso , Índice de Massa Corporal , Densidade Óssea , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prevalência , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/terapiaRESUMO
BACKGROUND: Little is known about the subtypes of type 2 diabetes (T2D) and their association with clinical outcomes in Asians. METHODS: We performed data-driven cluster analysis in patients with newly diagnosed drug-naive T2D (n = 756) from the Korean Genome and Epidemiology Study. Clusters were based on five variables (age at diagnosis, BMI, HbA1c, and HOMA2 ß-cell function, and insulin resistance). RESULTS: We identified four clusters of patients with T2D according to k-means clustering: cluster 1 (22.4 %, severe insulin-resistant diabetes [SIRD]), cluster 2 (32.7 %, mild age-related diabetes [MARD]), cluster 3 (32.7 %, mild obesity-related diabetes [MOD]), and cluster 4 (12.3 %, severe insulin-deficient diabetes [SIDD]). During 14 years of follow-up, individuals in the SIDD cluster had the highest risk of initiation of glucose-lowering therapy compared to individuals in the other three clusters. Individuals in the MARD and SIDD clusters showed the highest risk of chronic kidney disease and cardiovascular disease, and individuals in the MOD clusters showed the lowest risk after adjusting for other risk factors (P < 0.05). CONCLUSIONS: Patients with T2D can be categorized into four subgroups with different glycemic deterioration and risks of diabetes complications. Individualized management might be helpful for better clinical outcomes in Asian patients with different T2D subgroups.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Adulto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos Prospectivos , Insulina/uso terapêutico , Análise por Conglomerados , República da CoreiaRESUMO
Classifying patients with osteoporosis according to fracture risk and establishing adequate treatment strategies is crucial to effectively treat osteoporosis. The Korean Society for Bone and Mineral Research has issued a position statement regarding appropriate treatment strategies for postmenopausal osteoporosis. According to previous fragility fracture history, bone mineral density (BMD) test results, fracture risk assessment tool, and several clinical risk factors, fracture risk groups are classified into low, moderate, high, and very-high-risk groups. In high-risk groups, bisphosphonates (BPs) and denosumab are recommended as first-line therapies. Sequential BP treatment after denosumab discontinuation is required to prevent the rebound phenomenon. In the very high-risk group, anabolic drugs (teriparatide or romosozumab) are recommended as a first-line therapy; sequential therapy with antiresorptive agents is required to maintain BMD gain and reduce fracture risk. Fracture risk was reassessed annually, and the treatment plan was determined based on the results, according to the osteoporosis treatment algorithm for fracture risk.
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BACKGROUND: Peroxisome proliferator-activated receptor γ (PPARγ) activation suppresses HSC activation and liver fibrosis. Moreover, autophagy is implicated in hepatic lipid metabolism. Here, we determined whether PPARγ activation ameliorates HSC activation by downregulating transcription factor EB (TFEB)-mediated autophagy. METHODS AND RESULTS: Atg7 or Tfeb knockdown in human HSC line LX-2 cells downregulated the expression of fibrogenic markers including α smooth muscle actin, glial fibrillary acidic protein, and collagen type 1. Conversely, Atg7 or Tfeb overexpression upregulated fibrogenic marker expression. Rosiglitazone (RGZ)-mediated PPARγ activation and/or overexpression in LX-2 cells and primary HSCs decreased autophagy, as indicated by LC3B conversion, total and nuclear-TFEB contents, mRFP-LC3 and BODIPY 493/503 colocalization, and GFP-LC3 and LysoTracker colocalization. RGZ treatment decreased liver fat content, liver enzyme levels, and fibrogenic marker expression in high-fat high-cholesterol diet-fed mice. Electron microscopy showed that RGZ treatment restored the high-fat high-cholesterol diet-mediated lipid droplet decrease and autophagic vesicle induction in primary HSCs and liver tissues. However, TFEB overexpression in LX-2 cells offset the aforementioned effects of RGZ on autophagic flux, lipid droplets, and fibrogenic marker expression. CONCLUSIONS: Activation of PPARγ with RGZ ameliorated liver fibrosis and downregulation of TFEB and autophagy in HSCs may be important for the antifibrotic effects of PPARγ activation.
Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Células Estreladas do Fígado , PPAR gama , Animais , Humanos , Camundongos , Autofagia/genética , Células Estreladas do Fígado/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/patologia , PPAR gama/genética , PPAR gama/metabolismo , Rosiglitazona/farmacologia , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismoRESUMO
BACKGROUND: This study aimed to evaluate the effectiveness of bazedoxifene/vitamin D combination therapy in preventing osteoporosis in postmenopausal women with osteopenia. METHODS: This was an open-label, multicenter randomized-controlled, phase 4 clinical trial. Women between ages of 55 and 70 years in 9 medical tertiary centers in Korea were enrolled and assigned into 2 groups: an experiment group and a control group. The experimental group received bazedoxifene 20 mg/vitamin D 800 IU tablets for 6 months, and the control group received calcium 100 mg/vitamin D 1,000 IU tablets for 6 months. RESULTS: A total of 142 patients (70 in the experimental group and 72 in the control group) were included. The least-square mean±standard error of change in propeptide of type I collagen after 3 months was -6.87±2.56% in the experimental group and 1.22±2.54% in the control group. After 6 months, it was -21.07±2.75% in the experimental group and 1.26±2.71% in the control group. The difference between the 2 groups was -22.33% (p<0.01). The change of C-terminal telopeptide was -12.55±4.05% in the experimental group and 11.02±4.03% in the control group after 3 months. It was -22.0±3.95% and 10.20±3.89, respectively, after 6 months. The difference between the 2 groups was -32.21% (p<0.01) after 6 months. There was no significant difference in adverse events between the 2 groups. CONCLUSIONS: The osteoporosis preventive effect and safety of administering bazedoxifene/vitamin D combination pill were confirmed in postmenopausal women who needed osteoporosis prevention.
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The aims of this study were to investigate the validity of Friedewald's formula and to propose a range of triglyceride values over which the formula can be used without significant error. This was a cross-sectional analysis of 1,929 subjects (946 males and 983 females) aged 20 yr and older using data of the Korea National Health and Nutrition Examination Survey in 2009. Estimated total number was considered to be 10,633,655 (5,846,384 males and 4,787,271 females). Calculated and directly-measured low density lipoprotein cholesterol (LDL-C) values were highly correlated (r = 0.96); however, significant differences were observed between the directly-measured and calculated LDL-C concentrations. Subjects in the underestimated group (10.5%) had higher dysmetabolic profiles than those in the overestimated group (11.4%). Although serum triglyceride level showed the greatest independent association with differences between the calculated and directly-measured LDL-C concentrations, no statistically significant differences were noted when triglyceride concentration was between 36 and 298 mg/dL (93.2%). In conclusion, Friedewald's formula accurately estimates directly-measured serum LDL-C concentration in Korean adults. However, the formula can be applied to subjects with serum triglyceride concentrations from 36 to 298 mg/dL without significant error.
Assuntos
LDL-Colesterol/sangue , Triglicerídeos/sangue , Adulto , Povo Asiático , Índice de Massa Corporal , LDL-Colesterol/normas , Estudos Transversais , Feminino , Humanos , Hiperlipidemias/diagnóstico , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Valores de Referência , Análise de Regressão , República da Coreia , Triglicerídeos/normasRESUMO
BACKGROUND: We compared the efficacy of a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU to raloxifene 60 mg alone on vitamin D status, as indicated by change in serum 25-hydroxy-vitamin D (25[OH]D) levels. METHODS: In this 16-week, open-label, randomized, active controlled, multicenter clinical trial conducted in 4 university-affiliated hospitals in Korea, postmenopausal women aged 55 to 70 years with osteoporosis or osteopenia were randomly assigned in a 1:1 ratio to receive raloxifene 60 mg/cholecalciferol 800 IU combination therapy or raloxifene 60 mg monotherapy. Primary endpoint was change in serum 25(OH)D level from baseline to 16 weeks after the intervention. RESULTS: A total of 96 participants were randomly assigned to raloxifene/vitamin D combination therapy (N=49) and raloxifene monotherapy (N=47) groups. At week 16, serum 25(OH)D level increased from baseline, only in the raloxifene/vitamin D combination therapy group. Change in serum 25(OH)D level from baseline to week 16 was higher in the raloxifene/vitamin D combination therapy group (2.7±6.5 ng/mL) than in the raloxifene monotherapy (-1.7±6.2 ng/mL; P=0.0034) group. Proportions and number of adverse events (AEs) categorized by the System-Organ Class were not different between the groups. There was only one severe AE case (spondylolisthesis; raloxifene/vitamin D group), unlikely to be related to trial intervention. CONCLUSIONS: Among postmenopausal women with osteoporosis or osteopenia, a fixed dose combination of raloxifene 60 mg/vitamin D 800 IU showed superior efficacy in elevating serum 25(OH)D levels compared with raloxifene 60 mg alone during 16 weeks of follow-up. The safety of raloxifene/vitamin D combination was comparable to raloxifene alone.
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Pseudohypoparathyroidism (PHP) is a rare disorder that associates with resistance to parathyroid hormone (PTH). A 21-year old man visited outpatient clinic to treat previously diagnosed hypothyroidism and vitamin D deficiency. Despite daily 150 mcg of levothyroxine supplement, thyroid-stimulating hormone level was elevated, but thyroid autoantibodies were not detected. He showed features of Albright Hereditary Osteodystrophy and elevated serum PTH level with normal albumin-corrected calcium and phosphorus level. The Ellsworth-Howard test proved the blunted response of urinary phosphorus and cyclic adenosine monophosphate after the infusion of the exogenous PTH, suggesting PTH resistance. DNA analysis revealed a heterozygous mutation in the GNAS gene (c.478C > T). Herein, we report a case of PHP type 1a confirmed by clinical, biochemical and molecular analyses. Establishing correct diagnosis of PHP is necessary for efficient therapeutic management.
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This study used data from the Korea National Health and Nutrition Examination Survey IV-VII from 2007 to identify the prevalence of obesity and its phenotypes (metabolically unhealthy obesity [MUO] and metabolically healthy obesity [MHO]) and their secular changes. The prevalence of obesity in Korea increased with significant secular changes observed (ß=0.326, P trend <0.01) between 2007 and 2017, and especially in men (ß=0.682, P trend <0.001) but not in women. The changes in the prevalence of obesity during the study period were different between men and women (P=0.001). The prevalence of MUO significantly increased only in men (ß=0.565, P trend <0.01), while that of MHO increased only in women (ß=0.179, P<0.05), especially in the younger age group (ß=0.308, P<0.01).
Assuntos
Obesidade Metabolicamente Benigna , Obesidade , Feminino , Humanos , Inquéritos Nutricionais , Obesidade/epidemiologia , Obesidade Metabolicamente Benigna/epidemiologia , Fenótipo , PrevalênciaRESUMO
BACKGROUND/OBJECTIVES: The extract from Dendropanax morbifera exhibited diverse therapeutic potentials. We aimed to evaluate the efficacy and safety of D. morbifera leaf extract for improving metabolic parameters in human. SUBJECTS/METHODS: A 12-week, double blind, placebo-controlled and randomized trial included a total of 74 adults, and they were assigned to the placebo group (n = 38) or 700 mg/day of D. morbifera group (n = 36). The efficacy endpoints were changes in glycemic, lipid, obesity, and blood pressure (BP) parameters, in addition to the prevalence of metabolic syndrome (MetS) and the numbers of MetS components. Safety was assessed by monitoring adverse events (AEs). RESULTS: After 12 weeks of treatment, the hemoglobin A1c (HbA1c) level significantly decreased in the D. morbifera group compared to that of the placebo group (difference: -0.13 ± 0.20% vs. 0.00 ± 0.28%, P = 0.031; % of change: -2.27 ± 3.63% vs. 0.10 ± 5.10%, P = 0.025). The homeostatic model assessment for insulin resistance level also decreased significantly from its baseline in the D. morbifera group. The systolic BP of D. morbifera group decreased significantly than that of placebo group (difference: -3.9 ± 9.8 mmHg vs. 3.3 ± 11.7 mmHg, P = 0.005; % of change: -2.8 ± 7.7% vs. 3.3 ± 10.2%, P = 0.005). However, the lipid parameters and body composition including body weight did not differ between the groups. The prevalence of MetS (36.8% vs. 13.9%, P = 0.022) and the incidence of MetS (10.5% vs. 13.9%, P = 0.027) at 12 weeks was significantly lower in the D. morbifera group than it was in the placebo group. No serious AEs occurred in either group. CONCLUSIONS: Supplementation with D. morbifera extracts over a 12-week period improved metabolic parameters such as HbA1c and BP and reduced the prevalence of MetS. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0004672.
RESUMO
BACKGROUND: We performed a randomized, double-blind, prospective, 16-week clinical trial to evaluate the efficacy and safety of risedronate with and without cholecalciferol on 25-hydroxyvitamin D [25(OH)D] levels and bone markers in Korean patients with osteoporosis. METHODS: We randomly assigned 164 adults with osteoporosis to one of two treatment groups: weekly risedronate 35 mg and cholecalciferol 5600 IU combined in a single pill (RSD+) or weekly risedronate 35 mg alone (RSD). We measured serum levels of 25(OH)D, parathyroid hormone (PTH), and bone markers and performed muscle function tests, at baseline and after 16 weeks of treatment. RESULTS: After 16 weeks of treatment, mean serum 25(OH)D increased significantly from 39·8 to 70·8 nmol/l in the RSD+ group and declined significantly from 40·5 to 35 nmol/l in the RSD group. Although both treatment groups had significant increases in serum PTH over baseline during the study, the RSD group had a significantly larger increase than the RSD+ group (13·6 vs 4·8 ng/l; P = 0·0005). In both groups, serum bone-specific alkaline phosphatase (BSAP) and C-terminal telopeptide (CTX) declined rapidly; there were no significant differences between groups. There was also no significant difference between groups in lower-extremity function tests. The overall incidence of clinical adverse events was not significantly different between groups. CONCLUSION: In patients with osteoporosis, a once-weekly pill of risedronate and cholecalciferol provided equivalent antiresorptive efficacy to risedronate alone in terms of bone turnover and improved 25(OH)D level over a 16-week treatment period without significant adverse events.
Assuntos
Densidade Óssea/efeitos dos fármacos , Colecalciferol/uso terapêutico , Ácido Etidrônico/análogos & derivados , Osteoporose/tratamento farmacológico , Vitamina D/análogos & derivados , Idoso , Fosfatase Alcalina/sangue , Povo Asiático , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Colecalciferol/efeitos adversos , Colágeno Tipo I/sangue , Método Duplo-Cego , Quimioterapia Combinada , Ácido Etidrônico/efeitos adversos , Ácido Etidrônico/uso terapêutico , Feminino , Gastroenteropatias/induzido quimicamente , Humanos , Coreia (Geográfico) , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/etnologia , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/etnologia , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Estudos Prospectivos , Radioimunoensaio , Ácido Risedrônico , Resultado do Tratamento , Vitamina D/sangueRESUMO
Ghrelin functions as a neuroprotective agent and rescues neurons from various insults. However, the molecular mechanisms underlying ghrelin neuroprotection remains to be elucidated. An accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. Here, we report that acylated ghrelin inhibited tunicamycin- or thapsigargin-triggered ER stress-induced apoptotic cell death in primary rat cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), LY294002, showed that ghrelin prevented apoptosis via the activation of PI3K signaling pathway. Ghrelin suppressed tunicamycin- or thapsigargin-induced upregulation and nuclear translocation of C/EBP homologous protein (CHOP). Ghrelin also inhibited tunicamycin or thapsigargin induction of PRK-like ER kinase (PERK), eukaryotic translation initiation factor-2α (eIF2α) and activating transcription factor (ATF) 4. Exposure of cells to tunicamycin or thapsigargin resulted in nuclear translocation of forkhead box protein O1 (Foxo1), which was reduced by pretreatment with ghrelin. The protective effect of ghrelin was accompanied by an increased phosphorylation of Akt and glycogen synthase kinase (GSK)-3ß. Furthermore, ghrelin phosphorylated and inactivated pro-apoptotic BAD and Foxo1. In addition, phospho-Akt was translocated to the nucleus in response to ghrelin and PI3K inhibition by LY294002 prevented ghrelin-induced effect on phospho-Akt localization. Our study suggests that suppression of CHOP activation via the inhibition of PERK/eIF2α/ATF4 pathway and prevention of Foxo1 activation and nuclear translocation may contribute to ghrelin-mediated neuroprotection during ER stress responses. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3ß, BAD and Foxo1 may be associated with the anti-apoptotic effect of ghrelin.
Assuntos
Apoptose/efeitos dos fármacos , Retículo Endoplasmático/efeitos dos fármacos , Grelina/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Tapsigargina/farmacologia , Tunicamicina/farmacologia , Animais , Células Cultivadas , Córtex Cerebral/metabolismo , Cromonas/farmacologia , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Morfolinas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição CHOP/antagonistas & inibidores , Fator de Transcrição CHOP/metabolismo , eIF-2 Quinase/metabolismoRESUMO
BACKGROUND: Recent studies have shown that dysregulation of autophagy is involved in the development of nonalcoholic fatty liver disease (NAFLD). Transcription factors E3 (TFE3) and EB (TFEB) are master regulators of the transcriptional response of basic cellular processes such as lysosomal biogenesis and autophagy. Here, we investigated the role of fenofibrate, a PPARα agonist, in promotion of intracellular lipid clearance by upregulation of TFEB/TFE3. METHODS: We investigated whether the effects of fenofibrate on livers were dependent on TFEB in high fat diet (HFD)-fed mice and in vivo Tfeb knockdown mice. These mice were analyzed for characteristics of obesity and diabetes; the effects of fenofibrate on hepatic fat content, glucose sensitivity, insulin resistance, and autophagy functional dependence on TFEB were investigated. HepG2, Hep3B, TSC2+/+ and tsc2-/- MEFs, tfeb wild type- and tfeb knockout-HeLa cells were used for in vitro experiments. RESULTS: Fenofibrate treatment activated autophagy and TFEB/TFE3 and reduced hepatic fat accumulation in an mTOR-independent manner. Knockdown of TFEB offset the effects of fenofibrate on autophagy and hepatic fat accumulation. In addition, fenofibrate treatment induced lysosomal Ca2+ release through mucolipin 1, activated calcineurin and the CaMKKß-AMPK-ULK1 pathway, subsequently promoted TFEB and TFE3 dephosphorylation and nuclear translocation. Treatment with calcium chelator or knockdown of mucolipin 1 in hepatocytes offset the effects of fenofibrate treatment on autophagy and hepatic fat accumulation. CONCLUSION: Activation of PPARα ameliorates hepatic fat accumulation via activation of TFEB and lipophagy induction. Lysosomal calcium signaling appears to play a critical role in this process. In addition, activation of TFEB by modulating nuclear receptors including PPARα with currently available drugs or new molecules might be a therapeutic target for treatment of NAFLD and other cardiometabolic diseases.