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1. Utilizing nomograms to predict prevalent vertebral fracture risk: An analysis of dysmobility syndrome in a community-dwelling population

Author: Yu-Jr Lin, An-Shine Chao, Jung-Fu Chen, Alice Mk. Wong, Chen-Ming Sung, Fang-Ping Chen, and Yu-Ching Lin
Subjects: musculoskeletal diseases, Bone mineral, Fracture risk, medicine.medical_specialty, education.field_of_study, FRAX, business.industry, Osteoporosis, Population, General Medicine, Nomogram, medicine.disease, Preferred walking speed, Grip strength, Internal medicine, medicine, education, business
Abstract: Background To determine a reliable method to predict prevalent vertebral fractures (VF) by assessing the association between dysmobility syndrome (DS) and VF in a community-dwelling population. Material and methods This cross-sectional study enrolled 518 participants from fracture-prevention educational activities held in multiple communities in Taiwan. Assessments included questionnaires, fracture risk assessment tool (FRAX), bone mineral density (BMD) and body composition using dual-energy x-ray absorptiometry (DXA), lateral thoracolumbar spine x-rays (specifically T8-S1), grip strength (GS), walking speed, and fall history. Results DS was noted in 257 participants (49.6%) and VF was identified in 196 participants (37.8%). A higher prevalence of VF was noted in those with DS. The prevalence of VF was significantly associated with age, gender, FRAX both with and without BMD, osteoporosis, low GS, and DS. In multivariate models accounting for age and sex, the c-index was greater in those with low GS plus osteoporosis as compared to DS alone. Low GS, osteoporosis, and pre-BMD FRAX all had similar c-indexes. Pre-BMD FRAX plus low GS and osteoporosis was superior in predicting VF compared to pre-BMD FRAX plus low GS or osteoporosis alone. Besides the inclusion of age and gender, the nomogram with pre-BMD FRAX major osteoporosis fracture probability (MOF) plus low GS had improved correlation between the estimated and actual VF probability than those with pre-BMD FRAX MOF plus osteoporosis. Conclusions The constructed nomogram containing pre-BMD FRAX MOF plus low GS may be considered as a first-line prevalent VF screening method. Those with high-risk scores should subsequently undergo vertebral radiography and/or BMD.
Published: 2022
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2. The impact of bisphosphonates on mortality and cardiovascular risk among osteoporosis patients after cardiovascular disease

Author: Shu-Ting Wu, Jung-Fu Chen, and Chia-Jen Tsai
Subjects: medicine.medical_specialty, Acute coronary syndrome, Medicine (General), medicine.medical_treatment, Osteoporosis, Lower risk, 03 medical and health sciences, 0302 clinical medicine, R5-920, Internal medicine, Epidemiology, medicine, Bisphosphonate, Myocardial infarction, Mortality risk, business.industry, Atrial fibrillation, General Medicine, Cardiovascular outcome, medicine.disease, 030220 oncology & carcinogenesis, Heart failure, 030211 gastroenterology & hepatology, business
Abstract: Background/Purpose Bisphosphonates (BPs) impact on the survival and cardiovascular safety of osteoporosis patients after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) was evaluated. Methods A nationwide epidemiological study was conducted using the Taiwan National Health Insurance Research Database from 2000 to 2010. From the 1456 osteoporosis patients with previous ACS or AIS, mortality and cardiovascular safety was compared between 464 patients who used BPs and 464 patients who did not. Primary outcomes included all-cause mortality, and major adverse cardiovascular events. Results The BPs group had a lower risk of all-cause mortality than the control group after the 8-year follow-up (HR, 0.64; 95% CI, 0.46–0.88; P = 0.006). The risks of myocardial infarction, ischemic stroke, cardiovascular death, hospitalization for heart failure or other causes of mortality were similar across groups. However, there was a higher risk of hospitalization for atrial fibrillation in the BPs group than the control group (HR, 1.76; 95% CI, 1.26–2.46; P = 0.001). Conclusion Among osteoporosis patients after ACS or AIS, BPs use was associated with a reduced risk of all-cause mortality. However, patients with previous cardiovascular disease who received BP treatment should be careful about the risk of atrial fibrillation.
Published: 2021

3. Feasibility of combining heart rate variability and electrochemical skin conductance as screening and severity evaluation of cardiovascular autonomic neuropathy in type 2 diabetes

Author: Cheng-Hsien Lu, Chih-Cheng Huang, Nai-Wen Tsai, Wen-Chan Chiu, Yun-Ru Lai, Ben-Chung Cheng, Hsueh-Wen Chang, and Jung-Fu Chen
Subjects: Male, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Severity of Illness Index, 0302 clinical medicine, Diabetic Neuropathies, Heart Rate, Risk Factors, Outpatient clinic, Heart rate variability, Prospective Studies, food and beverages, General Medicine, Articles, Galvanic Skin Response, Prognosis, Clinical Science and Care, Cardiovascular Diseases, Cardiology, Original Article, Female, circulatory and respiratory physiology, medicine.medical_specialty, Cardiovascular autonomic neuropathy, 030209 endocrinology & metabolism, Electrochemical skin conductance, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Autonomic reflex, Humans, Aged, Autonomic nerve, business.industry, fungi, Electrochemical Techniques, medicine.disease, RC648-665, Diabetes Mellitus, Type 2, ROC Curve, Feasibility Studies, Autonomic neuropathy, business, Skin conductance, Follow-Up Studies
Abstract: Aims/Introduction Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics. Materials and Methods Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score. Results The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P
Published: 2021

4. Increased risk of end-stage renal disease in patients with systemic sclerosis

Author: Chun Yu Lin, Yu-Ting Su, Shan-Fu Yu, Jung-Fu Chen, Chung-Hsien Wu, Yu-Mu Chen, Chung-Yuan Hsu, and Tien-Tsai Cheng
Subjects: Male, medicine.medical_specialty, Immunology, Population, Taiwan, Subgroup analysis, End stage renal disease, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, medicine, Humans, Immunology and Allergy, Prospective Studies, 030212 general & internal medicine, skin and connective tissue diseases, education, Prospective cohort study, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, Scleroderma, Systemic, integumentary system, business.industry, Incidence, Hazard ratio, General Medicine, Confidence interval, Propensity score matching, Cohort, Kidney Failure, Chronic, business
Abstract: Objective: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc.Method: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD.Results: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80).Conclusion: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.
Published: 2021
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5. Long-term outcome and prognostic factors of single-dose Radioiodine Therapy in patients with Graves' disease

Author: Feng-Chih Shen, Jung-Fu Chen, Chia-Jen Tsai, Chen-Kai Chou, Cheng-Feng Taso, Yi-Ting Yang, Chih-Min Chang, Pei-Wen Wang, Shih-Chen Tung, Ming-Chun Kuo, and Shao-Wen Weng
Subjects: Adult, medicine.medical_specialty, Asia, Goiter, endocrine system diseases, Graves' disease, Taiwan, Disease, Tertiary referral hospital, Iodine Radioisotopes, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Radioiodine therapy, medicine, Humans, Retrospective Studies, Outcome, Univariate analysis, lcsh:R5-920, business.industry, Retrospective cohort study, General Medicine, Middle Aged, Prognosis, medicine.disease, Graves Disease, Regimen, Treatment Outcome, Goiter size, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, business, lcsh:Medicine (General)
Abstract: Background/purpose: Few studies exist investigating the effectiveness of radioiodine (RAI) therapy for hyperthyroidism patients in Asia. We herein investigated the real-world efficacy of single-dose RAI therapy in Taiwanese patients with Graves’ disease (GD). Methods: This is a retrospective study of 243 patients with GD recorded between 1989 and 2016 in a tertiary referral hospital. Eu- or hypothyroid after RAI therapy were defined as the successful group. Kaplan–Meier curve and cox-regression model were used for analysis of prognostic factors. Results: Of the 243 patients, 187 were females, with mean age of 46.9 ± 13.6 years. Most patients (63.8%) did not choose RAI as the first-line therapy. The median dose was 7 mCi, with a mean follow-up period of 107.1 ± 82.8 months. The overall success rate was 70.9%. Univariate analysis revealed calculated- or fixed-dose (P = 0.015), goiter size (P
Published: 2020

6. Association between Pro12Ala polymorphism and albuminuria in type 2 diabetic nephropathy

Author: Pei-Wen Wang, Chia‐Jen Tsa, Shih-Chen Tung, Ming-Chun Kuo, Cheng-Feng Taso, Feng-Chih Shen, Chen-Kai Chou, Jung-Fu Chen, Shao-Wen Weng, Chih-Min Chang, and Yung-Nien Chen
Subjects: Male, medicine.medical_specialty, Genotype, Endocrinology, Diabetes and Metabolism, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, Diseases of the endocrine glands. Clinical endocrinology, Diabetic nephropathy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Diabetic nephropathies, Odds Ratio, Prevalence, Internal Medicine, medicine, Albuminuria, Humans, Genetic Predisposition to Disease, Polymorphism, Alleles, Aged, Peroxisome proliferator‐activated receptor gamma, Polymorphism, Genetic, business.industry, Articles, General Medicine, Odds ratio, Middle Aged, RC648-665, medicine.disease, PPAR gamma, Clinical Science and Care, Diabetes Mellitus, Type 2, Case-Control Studies, Creatinine, Population study, Female, Original Article, medicine.symptom, business, Glomerular Filtration Rate
Abstract: Aims/Introduction Diabetic nephropathy (DN) is a complication of diabetes mellitus that is characterized by the gradual loss of kidney function, which results in increased levels of albumin in the urine. The Pro12Ala polymorphism in the peroxisome proliferator‐activated receptor‐γ2 gene has been confirmed to improve insulin sensitivity, but its association with susceptibility to DN in patients with type 2 diabetes remains inconclusive. Materials and Methods To examine whether the Pro12Ala polymorphism leads to the development of DN, a case‐control study was carried out in 554 patients with type 2 diabetes. The genotypes of Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor gamma 2 gene were analyzed by real‐time polymerase chain reaction with TaqMan® probe genotyping assay in all patients. Results The mean age of the study population was 57.7 ± 8.8 years, with average diabetes duration of 12.8 ± 6.9 years. The prevalence of albuminuria was 43.5%. The frequency of genotype Pro12Pro, Pro12Ala and Ala12Ala genotype were 92.6%, 7.0%, 0.4% in our study population, and 90.4%, 8.9% and 0.7% in normal urinary albumin‐to‐creatinine ratio group, respectively. The Ala carriers (Pro12Ala + Ala12Ala) had significantly lower urinary albumin‐to‐creatinine ratio (15.0 vs 20.5 mg/g, P = 0.001) and better renal function (estimated glomerular filtration rate 81.8 [69.8–97.6] vs 78.7 mL/min/1.73 m2 [61.6–96.2]; P = 0.05) compared with those with the genotype Pro12Pro. After adjustment for age, sex and other confounders, the odds ratio of albuminuria for the Ala12 allele was 0.428 (95% confidence interval 0.195–0.940, P = 0.034]). Conclusions Our results suggest that the peroxisome proliferator‐activated receptor gamma 2 Ala12 variant has significant protective effects against albuminuria and DN., The peroxisome proliferator‐activated receptor‐γ2 Ala12 variant has significant protective effects against albuminuria and diabetic nephropathy. These findings suggest that genetic screening can help in the development of personalized therapies for diabetes.
Published: 2020
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7. The role of blink reflex R1 latency as an electrophysiological marker in diabetic distal symmetrical polyneuropathy

Author: Nai-Wen Tsai, Yun-Ru Lai, Chih-Cheng Huang, Wei-Che Lin, Rue-Tsuan Liu, Pei-Wen Wang, Cheng-Hsien Lu, Jung-Fu Chen, Wen-Chan Chiu, Yu-Jih Su, Sheng-Yuan Hsiao, Chih-Min Su, Hung-Chen Wang, Jih-Yang Ko, and Ben-Chung Cheng
Subjects: Male, medicine.medical_specialty, genetic structures, Neural Conduction, Sensory system, Audiology, Sensitivity and Specificity, Severity of Illness Index, behavioral disciplines and activities, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Sural Nerve, Physiology (medical), mental disorders, Reaction Time, medicine, Humans, 0501 psychology and cognitive sciences, In patient, Corneal reflex, Latency (engineering), Neurologic Examination, Blinking, business.industry, musculoskeletal, neural, and ocular physiology, 05 social sciences, Middle Aged, medicine.disease, Sensory Systems, Electrophysiology, Facial Nerve, Diabetes Mellitus, Type 2, Neurology, Area Under Curve, Female, Neurology (clinical), business, Nerve conduction, Polyneuropathy, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN.A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS.Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS.Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN.Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect.
Published: 2020
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8. Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan Acromegaly Registry

Author: Jung-Fu Chen, Fen-Yu Tseng, Tien-Chun Chang, Szu-Tah Chen, Tien-Shang Huang, Pei-Wen Wang, Wayne Huey-Herng Sheu, and Jen-Der Lin
Subjects: Adult, Male, medicine.medical_specialty, Taiwan, Comorbidity, Affect (psychology), 03 medical and health sciences, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, Diabetes mellitus, Internal medicine, Acromegaly, Diabetes Mellitus, medicine, Humans, In patient, Registries, Insulin-Like Growth Factor I, lcsh:R5-920, Cerebral vascular accident, business.industry, General Medicine, Middle Aged, medicine.disease, Hormones, Cerebrovascular Disorders, 030220 oncology & carcinogenesis, Quality of Life, Female, 030211 gastroenterology & hepatology, Somatostatin, business, lcsh:Medicine (General)
Abstract: Background/Purpose: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). Results: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β = −4.720, p = 0.046 and β = −5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β = −5.839, p = 0.034 and β = −7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β = −26.632, p = 0.013; β = −28.353, p = 0.024; β = −25.648, p = 0.026; and β = −34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. Conclusion: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions. Keywords: Taiwan acromegaly registry, Quality of life, Clinical parameters
Published: 2019

9. Sural nerve sensory response in diabetic distal symmetrical polyneuropathy

Author: Jih-Yang Ko, Ben-Chung Cheng, Rue-Tsuan Liu, Chih-Min Su, Chih-Cheng Huang, Wei-Che Lin, Hsueh-Wen Chang, Nai-Wen Tsai, Hung-Chen Wang, Yun-Ru Lai, Cheng-Hsien Lu, Yu-Jih Su, Sheng-Yuan Hsiao, Wen-Chan Chiu, and Jung-Fu Chen
Subjects: Adult, Male, 0301 basic medicine, Aging, medicine.medical_specialty, Sensory Receptor Cells, Physiology, Neural Conduction, Action Potentials, Sural nerve, Sensory system, Type 2 diabetes, 030105 genetics & heredity, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Diabetic Neuropathies, Sural Nerve, Physiology (medical), Internal medicine, medicine, Humans, Prospective Studies, Aged, Aged, 80 and over, integumentary system, business.industry, Electrodiagnosis, musculoskeletal, neural, and ocular physiology, Snap, Middle Aged, medicine.disease, Axons, Cross-Sectional Studies, Diabetes Mellitus, Type 2, nervous system, Disease Progression, Sensory nerve action potential, Cardiology, Female, Neurology (clinical), business, Nerve conduction, Polyneuropathy, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: INTRODUCTION The sural sensory nerve action potential (SNAP) amplitude is a measure of the number of axons. We tested the hypothesis that sural SNAP amplitude can be used as a marker in screening, severity evaluation, and follow-up of diabetic distal symmetrical polyneuropathy (DSPN). METHODS Patients with type 2 diabetes underwent nerve conduction studies and were followed for 6 years. Composite amplitude scores (CASs) were determined to evaluate DSPN severity. RESULTS Sural SNAP amplitudes were negatively correlated with CAS (r = -.790, P
Published: 2019
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10. A registry of acromegaly patients and one year following up in Taiwan

Author: Fen-Yu Tseng, Tien-Chun Chang, Pei-Wen Wang, Szu-Tah Chen, Tien-Shang Huang, Jung-Fu Chen, Wayne Huey-Herng Sheu, and Jen-Der Lin
Subjects: Adenoma, Adult, Blood Glucose, Male, Galactorrhea, medicine.medical_specialty, Pediatrics, medicine.medical_treatment, Taiwan, Growth hormone, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Acromegaly, Epidemiology, medicine, Humans, Registries, Insulin-Like Growth Factor I, lcsh:R5-920, business.industry, General Medicine, Middle Aged, medicine.disease, Radiation therapy, Somatostatin, Growth Hormone, 030220 oncology & carcinogenesis, Cohort, Quality of Life, Female, 030211 gastroenterology & hepatology, Growth Hormone-Secreting Pituitary Adenoma, medicine.symptom, lcsh:Medicine (General), business, Follow-Up Studies
Abstract: Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life
Published: 2019
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11. Status of bone strength and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes

Author: Chih-Ming Fan, Yu-Ching Lin, Fang-Ping Chen, Sheng-Fong Kuo, and Jung-Fu Chen
Subjects: Aging, FRAX, Bone density, Osteoporosis, Dentistry, 030209 endocrinology & metabolism, Risk Assessment, Bone remodeling, Cohort Studies, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Trabecular bone score, Bone Density, Risk Factors, medicine, Humans, Aged, Bone mineral, 030219 obstetrics & reproductive medicine, business.industry, Incidence, Obstetrics and Gynecology, Middle Aged, medicine.disease, Postmenopause, Osteopenia, Cross-Sectional Studies, medicine.anatomical_structure, Diabetes Mellitus, Type 2, Cancellous Bone, Spinal Fractures, Female, Bone Remodeling, business, Cancellous bone, Osteoporotic Fractures
Abstract: Objective The aim of this study was to assess the status of bone mass, microarchitecture, and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes mellitus (T2DM). Methods We consecutively enrolled 285 women (aged 60.7 ± 6.9 y) with T2DM who underwent bone mineral density (BMD) and trabecular bone score (TBS) assessment using dual-energy x-ray absorptiometry; T8-S1 lateral spine radiographs; laboratory evaluation; and interviews regarding clinical risk factors based on the fracture risk assessment tool (FRAX). Results Low bone mass and deteriorated bone microarchitecture were observed in 63.2% and 72.6% of women with T2DM, respectively. TBS was correlated with lumbar spine, femoral neck, and total hip BMD. Significant differences in TBS were observed between the normal BMD, osteopenia, and osteoporosis groups. Age, vertebral fracture, and bone-specific alkaline phosphatase significantly differed among groups with different T scores or those classified by TBS categories. Bone-specific alkaline phosphatase was inversely correlated with BMD and TBS but positively with glycated hemoglobin. BMD showed a weaker correlation with vertebral fracture than TBS, TBS and BMD, FRAX, and TBS-adjusted FRAX. Conclusions Low bone mass and deteriorated TBS were noted in approximately two-thirds of T2DM women and was also associated with vertebral fracture. In addition to aging, poor glycemic control may play an important role in bone remodeling, which may be associated with changes in bone strength in T2DM women. Bone strength together with clinical risk factors has the strongest association with fracture, and may potentially be useful to identify women with T2DM at risk.
Published: 2019
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12. Mitochondrial haplogroups have a better correlation to insulin requirement than nuclear genetic variants for type 2 diabetes mellitus in Taiwanese individuals

Author: Tsu-Kung Lin, Jiin-Haur Chuang, Meng-Han Tsai, Sung-Chou Li, Pei-Wen Wang, Ching-Yi Lin, Chia-Wei Liou, Yu-Jih Su, Shun-Jen Chang, Jung-Fu Chen, Feng-Chih Shen, Shao-Wen Weng, and Yen-Hsiang Chang
Subjects: Male, Mitochondrial DNA, Endocrinology, Diabetes and Metabolism, Taiwan, Single-nucleotide polymorphism, Type 2 diabetes, DNA, Mitochondrial, Polymorphism, Single Nucleotide, Haplogroup, Diseases of the endocrine glands. Clinical endocrinology, Insulin resistance, Asian People, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Genetic Predisposition to Disease, Genetics, business.industry, Haplotype, Diabetes, Type 2 Diabetes Mellitus, High-Throughput Nucleotide Sequencing, General Medicine, Articles, Middle Aged, medicine.disease, RC648-665, Mitochondria, Clinical Science and Care, Diabetes Mellitus, Type 2, Haplotypes, Female, Original Article, Insulin Resistance, business, Human mitochondrial DNA haplogroup
Abstract: Aims/Introduction Identifying diabetes‐susceptible genetic variants will help to provide personalized therapy for the management of type 2 diabetes. Previous studies have reported a genetic risk score (GRS), computed by the sum of nuclear DNA (nDNA) risk alleles, that may predict the future requirement for insulin therapy. Although mitochondrial dysfunction has a close association with insulin resistance (IR), there are few studies investigating whether genetic variants of mitochondrial DNA (mtDNA) will affect the clinical characteristics of type 2 diabetes. Materials and Methods Mitochondrial haplogroups were determined using mtDNA whole genome next generation sequencing and 13 single nucleotide polymorphisms (SNPs) in nDNA susceptibility loci of 13 genes in 604 Taiwanese subjects with type 2 diabetes. A GRS of nDNA was computed by summation of the number of risk alleles. The correlation between the mtDNA haplogroup and the clinical characteristics of type 2 diabetes was assessed by logistic regression analysis. The results were compared with the GRS subgroups for the risk of insulin requirement. Results Mitochondrial haplogroups modulate the clinical characteristics of type 2 diabetes, in which patients harboring haplogroup D4, compared with those harboring non‐D4 haplotypes, were less prone to require insulin treatment, after adjusting for age, gender, and diabetes duration. However, there was no association between insulin requirement and GRS calculated from nuclear genetic variants. Conclusions Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement. The results highlight the role of mitochondria in the management of common metabolic diseases., Mitochondrial haplogroups, but not nuclear genetic variants, have a better association with the insulin requirement in patients with T2DM.
Published: 2021

13. 747-P: Improved Treatment Perceptions with IGlarLixi vs. Premix Insulin in Type 2 Diabetes (T2D) Uncontrolled on Basal Insulin (BI) + Oral Antihyperglycemic Drugs (OADs): Patient-Reported Outcomes (PROs) of the SoliMix Trial

Author: Julio Rosenstock, William H. Polonsky, Charlie Nicholls, Francesco Giorgino, Mathieu Coudert, Jung-Fu Chen, Agustina Alvarez, Katherine H. Whitmire, Rory J. McCrimmon, and Elisheva Lew
Subjects: medicine.medical_specialty, business.industry, Treatment adherence, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, Basal insulin, Insulin analog, Type 2 diabetes, medicine.disease, Multicenter study, Diabetes management, Family medicine, Diabetes mellitus, Internal Medicine, medicine, business
Abstract: Introduction: Treatment complexity can impact treatment adherence, which may affect clinical outcomes in people with T2D. This analysis assessed PROs in the SoliMix trial. Methods: SoliMix, an open-label, multicenter study, randomized adults with T2D and HbA1c ≥7.5-≤10 % on BI + OADs to once-daily iGlarLixi or twice-daily premix insulin analog (BiAsp 70/30). Between-treatment differences from baseline to Week 26 (W26) in Treatment-Related Impact Measure for Diabetes (TRIM-D) scores are shown overall and by domain. Global Treatment Effectiveness Evaluation (GTEE) endpoints were analyzed descriptively at W26. Results: As well as providing better glycemic control, iGlarLixi demonstrated greater improvement in each TRIM-D domain vs. BiAsp 70/30 from baseline to W26 (Figure), with the greatest differences seen in diabetes management and treatment burden scores. GTEE scores also showed a greater proportion of participants and physicians who rated complete or marked improvement of diabetes control with iGlarLixi (81% and 83%) vs. BiAsp 70/30 (63% and 65%) at W26. Conclusions: Advancing BI with iGlarLixi resulted in a greater positive impact than with premix 70/30 for people with T2D uncontrolled on BI + OADs, suggesting a potentially lower treatment burden with iGlarLixi. Disclosure W. H. Polonsky: Advisory Panel; Self; Intarcia Therapeutics, Inc., Consultant; Self; Abbott Diabetes, ADOCIA, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Insulet Corporation, Lilly Diabetes, Novo Nordisk, Onduo LLC., Sanofi US. J. Rosenstock: Board Member; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Consultant; Self; Applied Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Inc., Sanofi, Research Support; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Genentech, Inc., Intarcia Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Oramed Pharmaceuticals, Inc., Pfizer Inc., REMD Biotherapeutics, Sanofi. R. J. Mccrimmon: Advisory Panel; Self; Novo Nordisk Inc., Sanofi-Aventis, Board Member; Self; Novo Nordisk Foundation, Research Support; Self; AstraZeneca. K. H. Whitmire: None. F. Giorgino: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Roche Diabetes Care, Sanofi, Research Support; Self; Lilly Diabetes, Roche Diabetes Care. J. Chen: None. C. Nicholls: Employee; Self; Sanofi. E. Lew: Employee; Self; Sanofi. A. Alvarez: Employee; Self; Sanofi. M. Coudert: Employee; Self; Sanofi. Funding Sanofi (EudraCT 2017-003370-13)
Published: 2021
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14. Response to letter to the editor 'the impact of bisphosphonates on mortality and cardiovascular risk among osteoporosis patients after cardiovascular disease'

Author: Shu-Ting Wu, Chia-Jen Tsai, and Jung-Fu Chen
Subjects: Medicine (General), medicine.medical_specialty, Letter to the editor, Bone Density Conservation Agents, Diphosphonates, business.industry, Osteoporosis, MEDLINE, General Medicine, Disease, medicine.disease, R5-920, Cardiovascular Diseases, Heart Disease Risk Factors, Risk Factors, medicine, Humans, Intensive care medicine, business
Published: 2021

15. Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan

Author: Chung Sen Chen, Szu Ta Chen, Ju Ying Jiang, Yi Sun Yang, Jung Fu Chen, Yi Jen Hung, Ching Ling Lin, Chun Chuan Lee, Chin Hsiao Tseng, Ting I. Lee, Shih Te Tu, Pi Jung Hsiao, Chieh Hsiang Lu, Yun Shing Peng, Ching-Chu Chen, Pei Chi Chen, Yung Chuan Lu, and Chwen Yi Yang
Subjects: medicine.medical_specialty, Drugs and Devices, HbA1c, endocrine system diseases, lcsh:Medicine, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Weight loss, Internal medicine, Evidence Based Medicine, Type 2 diabetes mellitus, medicine, Internal Medicine, Dapagliflozin, Glycemic, Real-world evidence, business.industry, General Neuroscience, lcsh:R, Type 2 Diabetes Mellitus, Retrospective cohort study, General Medicine, Confidence interval, Diabetes and Endocrinology, Blood pressure, chemistry, Glycated hemoglobin, medicine.symptom, General Agricultural and Biological Sciences, business, SGLT2 inhibitors
Abstract: Aims/Introduction To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. Materials and Methods In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. Results A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by −0.73% (95% confidence interval [CI] −0.80, −0.67), body weight was -1.61 kg (95% CI −1.79, −1.42), and systolic/diastolic blood pressure by −3.6/−1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (−0.82%) than switched therapy (−0.66%) (p = 0.002). The proportion of patients achieving HbA1c Conclusions In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.
Published: 2020

16. Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

Author: Wei-Che Lin, Meng Hsiang Chen, Wen-Chan Chiu, Nai-Wen Tsai, Ben-Chung Cheng, Jung-Fu Chen, Yun-Ru Lai, Cheng-Hsien Lu, and Chih-Cheng Huang
Subjects: Leptin, medicine.medical_specialty, Mediation (statistics), Waist, Cardiovascular autonomic neuropathy, lcsh:Medicine, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, Body Mass Index, Prediabetic State, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Prediabetes, Cardiac autonomic reflex tests, Longitudinal Studies, Composite autonomic scoring scale, business.industry, Research, lcsh:R, fungi, Type 2 Diabetes Mellitus, food and beverages, Type 2 diabetes and prediabetes, General Medicine, medicine.disease, Obesity, Endocrinology, Diabetes Mellitus, Type 2, Central obesity, Obesity, Abdominal, Waist circumference, business
Abstract: Background Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. Methods The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value). Results A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P Conclusions Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.
Published: 2020

17. Pharmacologic intervention for prevention of fractures in osteopenic and osteoporotic postmenopausal women: Systemic review and meta-analysis

Author: Ding-Cheng Chan, Rong-Sen Yang, Michael R. McClung, Weibo Xia, Keh-Sung Tsai, Shih Te Tu, Kun Ling Wu, Jung Fu Chen, Jawl Shan Hwang, Tsung Ting Tsai, Wei Chieh Hung, Toshio Matsumoto, Wing P. Chan, Chung-Hwan Chen, Chun Feng Huang, Nelson B. Watts, John A. Kanis, Eugene V. McCloskey, Yoon Sok Chung, Yin Fan Chang, Ing Lin Chang, Cyrus Cooper, and Chih Hsing Wu
Subjects: 0301 basic medicine, musculoskeletal diseases, medicine.medical_specialty, Low bone mass, lcsh:Diseases of the musculoskeletal system, Endocrinology, Diabetes and Metabolism, Osteoporosis, 030209 endocrinology & metabolism, Placebo, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Clinical endpoint, Orthopedics and Sports Medicine, Raloxifene, Bone mineral, Primary prevention, business.industry, Osteopenia, Incidence (epidemiology), medicine.disease, Fracture, Meta-analysis, 030101 anatomy & morphology, lcsh:RC925-935, business, medicine.drug
Abstract: Objectives Emerging evidence has indicated a role for pharmacologic agents in the primary prevention of osteoporotic fracture, but have not yet been systematically reviewed for meta-analysis. We conducted a meta-analysis to evaluate the efficacy of pharmacologic interventions in reducing fracture risk and increasing bone mineral density (BMD) in postmenopausal women with osteopenia or osteoporosis but without prevalent fragility fracture. Method The Medline, EMBASE, and CENTRAL databases were searched from inception to September 30, 2019. Only randomized placebo-controlled trials evaluating postmenopausal women with −1.0 > bone mineral density (BMD) T-score > −2.5 (low bone mass) and those with BMD T-score ≤ −2.5 (osteoporosis) but without baseline fractures, who were receiving anti-osteoporotic agents, providing quantitative outcomes data and evaluating risk of vertebral and/or non-vertebral fragility fracture at follow-up. The PRISMA guidelines were followed, applying a random-effects model. The primary endpoint was the effect of anti-osteoporotic regimens in reducing the incidence of vertebral fractures. Secondary endpoints were percentage changes in baseline BMD at the lumbar spine and total hip at 1 and 2 years follow up. Results Full-text review of 144 articles yielded, 20 for meta-analysis. Bisphosphonates reduced the risk of vertebral fracture (pooled OR = 0.50, 95%CIs = 0.36–0.71) and significantly increased lumbar spine BMD after 1 year, by 4.42% vs placebo (95%CIs = 3.70%–5.14%). At the hip, this value was 2.94% (95%CIs = 2.13%–3.75%). Overall results of limited studies for non-bisphosphonate drugs showed increased BMD and raloxifene significantly decreases the risk of subsequent clinical vertebral fractures. Conclusion The bisphosphonates are efficacious and most evident for the primary prevention of osteoporotic vertebral fractures, reducing their incidence and improving BMD in postmenopausal women with osteopenia or osteoporosis., Highlights • Bisphosphonates reduced the risk of vertebral fracture in postmenopausal women with osteopenia or osteoporosis but without fracture. • Bisphosphonates increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Limited studies for non-bisphosphonate drugs showed increased BMD in postmenopausal women with osteopenia or osteoporosis but without fracture. • Raloxifene decreased the risk of clinical vertebral fractures in postmenopausal women with osteopenia or osteoporosis but without fracture.
Published: 2020

18. Peri-renal fat thickness is positively associated with the urine albumin excretion rate in patients with type 2 diabetes

Author: Feng-Chih Shen, Jung-Fu Chen, and Ben-Chung Cheng
Subjects: 0301 basic medicine, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Urology, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, Kidney, Adipose capsule of kidney, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Albumins, Medicine, Albuminuria, Humans, Diabetic Nephropathies, 030109 nutrition & dietetics, Nutrition and Dietetics, urogenital system, business.industry, Type 2 Diabetes Mellitus, Odds ratio, respiratory system, medicine.disease, respiratory tract diseases, medicine.anatomical_structure, Adipose Tissue, Diabetes Mellitus, Type 2, medicine.symptom, business
Abstract: Backgrounds Albuminuria, the earliest clinical manifestation of diabetic kidney disease (DKD), is a major prognostic indicator of renal progression. Obesity itself is associated with the development of DKD and accelerates its progression. Accumulation of peri-renal fat on the kidneys can damage kidney function. Measuring the perirenal fat thickness (PFT) by ultrasound is a non-invasive method to measure ectopic fat deposition on the kidney. In this study, we aim to obtain the association between albuminuria and PFT. Methods Eighty-nine subjects with type 2 diabetes mellitus (T2DM) were enrolled. Albuminuria was defined as a urine albumin-to-creatinine ratio (UACR) ≧30 mg/g. Measurement of the PFT was performed by B-mode ultrasound (Toshiba SSA-680A) and determined from the surface of the abdominal musculature to the surface of kidney. Pearson correlation coefficients were determined to test the significant independent relationship between the PFT and demographic, anthropometric and laboratory parameters. Results Patients were divided into those with (n = 66) and without (n = 23) albuminuria. PFT (odds ratio [OR], 19.3; 95% CI, 2.25–165.00; p = 0.01) was significantly correlated with albuminuria based on multiple logistic regression analysis. Additionally, linear regression confirmed that degree of albuminuria has a positive association with the PFT (r = 0.233; p = 0.03). Conclusions Our study showed that an increased PFT is positively associated with the albuminuria among patients with T2DM. Our findings suggest that measurement of the PFT may represent a helpful tool to assess the risk of developing albuminuria in patients with T2DM.
Published: 2020

19. Associations between adipocytokines and severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes

Author: Yun-Ru Lai, Jung-Fu Chen, Ben-Chung Cheng, Wen-Chan Chiu, Chih-Cheng Huang, Cheng-Hsien Lu, and Nai-Wen Tsai
Subjects: medicine.medical_specialty, business.industry, Internal medicine, medicine, Cardiology, Adipokine, Type 2 diabetes, Prediabetes, Autonomic neuropathy, medicine.disease, business
Abstract: Background It is thought that adipocytokines contribute to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). We aimed to identify adipocytokines that are associated with the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. Methods The complete cardiovascular autonomic function and biomarkers were assessed for each patient. The severity of CAN was assessed using both the composite autonomic scoring scale (CASS) and the cardiac autonomic reflex tests (CARTs) score. Biomarkers included adipocytokines (leptin, chemerin, adiponectin, and vaspin), oxidative stress (thiols and thiobarbituric acid-reactive substance [TBARS]), endothelial dysfunction (sICAM-1 and sVCAM-1), and insulin resistance (triglyceride/high-density lipoprotein cholesterol [HDL-C] ratio and homeostasis model assessment of insulin resistance [HOMA-IR] index). Results A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. Stepwise logistic regression showed that diabetes duration and leptin level were independently associated with the presence of CAN. Leptin level was positively correlated with body mass index (r = 0.588, P
Published: 2020
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20. Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment

Author: Chii-Min Hwu, Chih-Yuan Wang, Shih-Te Tu, Yi-Jen Hung, Wayne Huey-Herng Sheu, Kai-Jen Tien, Ching-Chu Chen, Chao-Hung Wang, Yu-Yao Huang, Pi-Jung Hsiao, and Jung-Fu Chen
Subjects: medicine.medical_specialty, Asia, Insulin glargine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Insulin analog, 030209 endocrinology & metabolism, Review Article, Type 2 diabetes, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Diabetes management, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Intensive care medicine, Glycemic, business.industry, Insulin, Diabetes, General Medicine, Prognosis, RC648-665, medicine.disease, Asians, Basal (medicine), business, Needs Assessment, medicine.drug
Abstract: Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.
Published: 2019
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21. Challenges and unmet needs in basal insulin therapy: lessons from the Asian experience

Author: Jung Fu Chen, Su-Yen Goh, Maria Aileen Mabunay, Wing Bun Chan, Sony Wibisono Mudjanarko, Pongamorn Bunnag, Shailendra Bajpai, Iris Thiele Isip-Tan, and Thi Thanh Huyen Vu
Subjects: Insulin degludec, medicine.medical_specialty, medicine.medical_treatment, 030209 endocrinology & metabolism, Review, Type 2 diabetes, Hypoglycemia, patient education, insulin detemir, insulin titration, 03 medical and health sciences, 0302 clinical medicine, insulin degludec, Diabetes mellitus, Internal Medicine, medicine, 030212 general & internal medicine, Intensive care medicine, Glycemic, Insulin detemir, Pharmacology, business.industry, Insulin glargine, Insulin, insulin glargine, medicine.disease, business, medicine.drug
Abstract: Basal insulin therapy can improve glycemic control in people with type 2 diabetes. However, timely initiation, optimal titration, and proper adherence to prescribed basal insulin regimens are necessary to achieve optimal glycemic control. Even so, glycemic control may remain suboptimal in a significant proportion of patients. Unique circumstances in Asia (eg, limited resources, management of diabetes primarily in nonspecialist settings, and patient populations that are predominantly less educated) coupled with the limitations of current basal insulin options (eg, risk of hypoglycemia and dosing time inflexibility) amplify the challenge of optimal basal insulin therapy in Asia. Significant progress has been made with long-acting insulin analogs (insulin glargine 100 units/mL and insulin detemir), which provide longer coverage and less risk of hypoglycemia over intermediate-acting insulin (Neutral Protamine Hagedorn insulin). Furthermore, recent clinical evidence suggests that newer long-acting insulin analogs, new insulin glargine 300 units/mL and insulin degludec, may address some of the unmet needs of current basal insulin options in terms of risk of hypoglycemia and dosing time inflexibility. Nevertheless, more can be done to overcome barriers to basal insulin therapy in Asia, through educating both patients and physicians, developing better patient support models, and improving accessibility to long-acting insulin analogs. In this study, we highlight the unique challenges associated with basal insulin therapy in Asia and, where possible, propose strategies to address the unmet needs by drawing on clinical experiences and perspectives in Asia.
Published: 2017
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22. HbA1C Variability Is Strongly Associated with Development of Macroalbuminuria in Normal or Microalbuminuria in Patients with Type 2 Diabetes Mellitus: A Six-Year Follow-Up Study

Author: Yun-Ru Lai, Cheng-Hsien Lu, Chih-Cheng Huang, Wen-Chan Chiu, Jung-Fu Chen, and Ben-Chung Cheng
Subjects: Blood Glucose, Male, endocrine system diseases, Type 2 diabetes, 030204 cardiovascular system & hematology, Kidney, Kidney Function Tests, urologic and male genital diseases, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Prospective Studies, Prospective cohort study, Aged, 80 and over, General Medicine, Middle Aged, female genital diseases and pregnancy complications, Creatinine, Disease Progression, Medicine, Female, Research Article, Glomerular Filtration Rate, Adult, medicine.medical_specialty, Article Subject, Taiwan, Renal function, 030209 endocrinology & metabolism, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Albumins, Internal medicine, medicine, Albuminuria, Humans, Aged, Glycemic, Glycated Hemoglobin, General Immunology and Microbiology, business.industry, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, medicine.disease, Diabetes Mellitus, Type 2, chemistry, Uric acid, Microalbuminuria, business, Follow-Up Studies
Abstract: Background. Glycemic variability is associated with higher risk of microvascular complications in patients with type 2 diabetes. Aim. To test the hypothesis that glycemic variability can contribute to progression to macroalbuminuria in normal or microalbuminuria in patients with type 2 diabetes. Design. This prospective study enrolled 193 patients with type 2 diabetes at a tertiary medical center. Methods. For each patient, the intrapersonal glycemic variability (mean, SD, and coefficient of variation of HbA1c) was calculated using all measurements obtained three years before the study. Patients were divided into four groups stratified by both urine albumin/creatinine ratio and HbA1c-SD. The presence of macroalbuminuria was assessed with Kaplan–Meier plots and compared by log-rank test. Results. Of the 193 patients, 83 patients were in the macroalbuminuria state. Patients in the initial macroalbuminuria group after enrollment had the highest diabetes duration, mean, CV-HbA1c and HbA1c-SD, and uric acid level, and the lowest estimate glomerular filtration rate, followed by subsequent macroalbuminuria and without macroalbuminuria groups. Patients with microalbuminuria and high HbA1c-SD showed the highest progression rate to macroalbuminuria, after a six-year follow-up study by Kaplan–Meier Plots and compared by log-rank test. Conclusions. Higher HbA1C variability is more likely to progress to macroalbuminuria in those patients who are already in a microalbuminuria state. We recommend that clinicians should aggressively control blood glucose to an acceptable range and avoid blood glucose fluctuations by individualized treatment to prevent renal status progression.
Published: 2020

23. Effects of Resistance Exercise on Glycated Hemoglobin and Functional Performance in Older Patients with Comorbid Diabetes Mellitus and Knee Osteoarthritis: A Randomized Trial

Author: Shu-Mei Chen, Wen-Dien Chang, Feng-Chih Shen, Jung-Fu Chen, and Nai-Jen Chang
Subjects: Male, medicine.medical_specialty, WOMAC, endocrine system diseases, Health, Toxicology and Mutagenesis, Population, lcsh:Medicine, physical activity, 030209 endocrinology & metabolism, Isometric exercise, Osteoarthritis, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Medicine, Humans, education, Aged, Glycated Hemoglobin, Ontario, therapeutic exercise, education.field_of_study, diabetes, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, Resistance Training, 030229 sport sciences, Middle Aged, Osteoarthritis, Knee, Physical Functional Performance, medicine.disease, osteoarthritis, chemistry, Diabetes Mellitus, Type 2, Physical therapy, Female, Glycated hemoglobin, business, human activities, performance
Abstract: Type 2 diabetes mellitus (T2DM) is significantly associated with osteoarthritis (OA). This study investigated the effects of two resistance exercise approaches on glycated hemoglobin (HbA1c) level and function performance. Enrolled were 70 older patients with both T2DM and knee OA. The dynamic group performed resistance exercises with an elastic resistance band. The isometric group underwent isometric contraction exercises. After the 12-week intervention, a significant within-group improvement (all p &lt, 0.001) was observed for the chair stand test (CST, 10.8%, vs. 7.1%), timed up and go (TUG) test (12.6% vs. 7.6%), Western Ontario and McMaster Universities Osteoarthritis (WOMAC) physical function subscale (62.3% vs. 36.1%), and overall WOMAC (54.5% vs. 34.5%) in the dynamic and isometric group, respectively. In addition, in terms of between-group differences, the dynamic group had significant improvements in CST (p = 0.011), TUG (p &lt, 0.001), WOMAC physical function subscale (p = 0.033), and overall WOMAC (p = 0.036) scores compared with the isometric group. However, no significant change in HbA1c was observed in either group. In conclusion, the dynamic resistance exercise significantly improved muscle strength, dynamic balance, and physical function in this comorbid population, however, there was no notable difference in change in HbA1c among different resistance exercises.
Published: 2019

24. Severity of Cardiovascular Autonomic Neuropathy Is a Predictor Associated With Major Adverse Cardiovascular Events in Adults With Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

Author: Cheng-Hsien Lu, Chih-Cheng Huang, Yun-Ru Lai, Jung-Fu Chen, Nai-Wen Tsai, Wen-Chan Chiu, Ben-Chung Cheng, and Hsueh-Wen Chang
Subjects: Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Myocardial Infarction, Taiwan, 030209 endocrinology & metabolism, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetic Neuropathies, Risk Factors, Internal medicine, Diabetes mellitus, Case fatality rate, Internal Medicine, Medicine, Humans, cardiovascular diseases, 030212 general & internal medicine, Myocardial infarction, Mortality, Prospective cohort study, Aged, Aged, 80 and over, business.industry, Proportional hazards model, Incidence (epidemiology), Incidence, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Stroke, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Cardiology, Female, business, Mace, Diabetic Angiopathies, Follow-Up Studies
Abstract: Cardiovascular autonomic function impairment has been reported in patients with type 2 diabetes mellitus and is associated with cardiovascular events. In this study, we test the hypothesis that the severity of cardiovascular autonomic neuropathy is a predictor associated with subsequent 3-point major adverse cardiovascular events (3-P MACE; combined endpoint of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke).In this prospective study, we enrolled 168 patients with type 2 diabetes mellitus over a 6-year follow-up period. We constructed the Composite Autonomic Scoring Scale as a measure of the severity of cardiovascular autonomic neuropathy and examined baseline clinical and laboratory data of 168 patients with diabetes. Cardiovascular autonomic testing included heart rate response to deep breathing, Valsalva ratio and baroreflex sensitivity. Therapeutic outcome was defined as 3-P MACE.The overall incidence of new 3-P MACE was 23.2% and overall fatality rate was 9.5% during the 6-year follow-up period. Only underlying coronary heart disease and Composite Autonomic Scoring Scale were independently associated with subsequent 3-P MACE in the Cox proportional hazards model. Any increase of 1 point in Composite Autonomic Scoring Scale would increase the risk of new 3-P MACE by 9.7%. Area under the curve on receiver-operating characteristic curve analysis was 0.72 in predicting subsequent 3-point MACE in combined heart rate response to deep breathing and Valsalva ratio.Besides underlying coronary heart disease, the severity of cardiovascular autonomic neuropathy is strongly associated with subsequent 3-P MACE. Combined heart rate response to deep breathing and Valsalva ratio testing can increase sensitivity and specificity in predicting subsequent 3-point MACE, and it can serve as a time-effective cardiovascular autonomic screening service in the outpatient clinic sitting.
Published: 2019

25. Odanacatib for the treatment of postmenopausal osteoporosis: results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Author: Michael R McClung, Michelle L O'Donoghue, Socrates E Papapoulos, Henry Bone, Bente Langdahl, Kenneth G Saag, Ian R Reid, Douglas P Kiel, Ilaria Cavallari, Marc P Bonaca, Stephen D Wiviott, Tobias de Villiers, Xu Ling, Kurt Lippuner, Toshitaka Nakamura, Jean-Yves Reginster, Jose Adolfo Rodriguez-Portales, Christian Roux, José Zanchetta, Cristiano A F Zerbini, Jeong-Gun Park, KyungAh Im, Abby Cange, Laura T Grip, Norman Heyden, Carolyn DaSilva, Dosinda Cohn, Rachid Massaad, Boyd B Scott, Nadia Verbruggen, Deborah Gurner, Deborah L Miller, Micki L Blair, Adam B Polis, S Aubrey Stoch, Arthur Santora, Antonio Lombardi, Albert T Leung, Keith D Kaufman, Marc S Sabatine, Carlos Alfredo Mautalén, Zulema Man, Jose Ruben Zanchetta, Clelia Haydee Magaril, Philip Sambrook, Piet Geusens, Stefan Goemaere, Ben Hur Albergaria, Cristiano Augusto de Freitas Zerbini, Marise Lazaretti Castro, Luiz Henrique Gregorio, Rumen Stoilov, Anna-Maria I Borissova, Kiril Hristov Hristozov, Nataliya L Temelkova, Ivona Kirilova Daskalova, Stefka Ivanova Kuzmanova, Daniela Yaneva-Bichovska, Anastas Zgurov Batalov, Pablo Riedemann, José Adolfo Rodriguez Portales, Hai Tang, hanmin Zhu, Zhenlin Zhang, Aijun Chao, Yali Hu, Zhiming Liu, Juming Lu, Mingcai Qiu, Xin Gao, Shaofen Zhang, Ling Xu, Weibo Xia, Eryuan Liao, Wenying Yang, Wen Wu, Kerong Dai, Renming Hu, Juan Jose Jaller, Francisco Cabal, José Fernando Molina, Carlos A Cure Cure, Hernan Yupanqui-Lozno, Philippe Chalem, John Londono, Mauricio Abello, Edgardo D Tobias, William Otero, Tatjana Nikolic, Blazenka Miskic, Jan Stepan, Vaclav Vyskocil, Libor Novosad, Jan Slesinger, Pavel Novosad, Erika Vlckova, Ladislav Bortlik, Eva Dokoupilova, Tomas Hala, Jens-Erik Beck Jensen, Kim Torsten Brixen, Bente Lomholt Langdahl, Peter Schwarz, Peter Claes Eskildsen, Pia Agnete Eiken, Anne Pernille Hermann, Jeppe Gram, Maiken Brix Schou, Peter Alexandersen, Bettina Nedergaard, Dolores Magdalena Mejía, Lourdes Estrella De Henriquez, Norka Páez, Casimiro Velazco, Ivo Valter, Kadri-Liina Vahula, Ingrid Kull, Katre Maasalu, Roland Chapurlat, Patrice Fardellone, Claude Laurent Benhamou, Georges Weryha, Volkmar Herkt, Rene Martz, Ruth Nischik, Wolfgang Spieler, Christel Contzen, Dieter Felsenberg, Isolde Frieling, Eike Frahm, Henry Briones, Boris Sandoval, Patricia Barrios, Abraham García, Carlos Avendaño, Magdalena González, Jeremías Guerra, Maria Tuna, Olga Marina Díaz, Eduardo Samayoa, Edgar López, José Raúl Barrera, Mainor Palencia, Mayra Cifuentes, Georgina Alvarado, Miriam López, Nilmo Chavez, Franklin Haase, Ruddy Rivera, Claudio González, Kathryn Tan, Ping Chung Leung, Sheshadri Mandalam, Shailesh Umakant Pitale, Ganapathi Bantwal, Ariachery Chinamma Ammini, Shehla Sajid Akhta Shaikh, Prasanna Kumar Kanakatte Mylariah, Mala Dharmalingam, Satinath Mukhopadhyay, Arpit Jain, Parminder Singh, Naresh Shetty, Srikanta Shamanna Sathyanarayana, Nalini Shah, Manoj Dharam Chadha, Rajendra Bhandankar, Kumaravel Velayutham, Sudha Marwah, Mathew John, Rakesh Kumar Sahay, Silvano Adami, Ranuccio Nuti, Gerolamo Bianchi, Maria Luisa Brandi, Salvatore Minisola, Carmelo Erio Fiore, Alessandro Rubinacci, Hisayuki Miyajima, Hiroo Yamane, Yuji Nakatani, Sumiaki Okamoto, Koji Kuroda, Motoaki Fujimori, Akira Itabashi, Kuniaki Katayama, Satoru Nakajo, Yoshiaki Somekawa, Yoshimitsu Ohsawa, Wataru Tajima, Katsunori Mizuno, Shigeru Mori, Takato Kanabuchi, Hiroyuki Hashizume, Nobuyuki Oka, Kazutoshi Hamada, Motoi Yamaguchi, Fumiki Hirahara, Masaaki Atobe, Yoshiharu Ohtake, Shuichi Ichikawa, Tomoyuki Onishi, Kou Matsumoto, Tetsuro Nakamura, Eishi Shirasawa, Ko Katayama, Mitsugu Takahashi, Tadanori Oguma, Hideo Matsui, Yoshiharu Katoh, Keiichi Shigenobu, Tsutomu Onishi, Masato Shibukawa, Satoshi Ikeda, Kazuhiro Osaka, Ryosuke Kanda, Yoshito Inobe, Masaharu Shigenobu, Morimasa Hasegawa, Tetsuo Yamaji, Yu Miyazaki, Takayasu Ito, Eisuke Nakamura, Shinji Nagai, Sung-Kil Lim, Yoon-Sok Chung, Chan-Soo Shin, Yong-Ki Min, Ghi Su Kim, Hyun Koo Yoon, Moo-Il Kang, Kyu-Hyun Yang, Hyoung Moo Park, In Joo Kim, Dong Jin Chung, Ho Yeon Chung, Sandra Jaundzeikare, Dace Andersone, Agita Medne, Yasser Yaghi, Vidmantas Alekna, Vytautas Kasiulevicius, Irina Purtokaite - Labutiniene, Aurelija Krasauskiene, Jurate Varanaviciene, Vida Basijokiene, Agne Abraitiene, Lina Radzeviciene, Jesus Walliser, Pedro Alberto García Hernández, Maria Frida Araujo, Hilario Ernesto Avila Armengol, Pilar De la Peña, Juan Tamayo, Beatriz Zazueta, Fidencio Cons, Nigel Leslie Gilchrist, Ian Reginald Reid, Robert Leikis, Peter Jones, Joe Gragrath Pradeep Singh, Johan Inge Halse, Unni Syversen, Hans Olav Høivik, Erik Snorre Øfjord, Hans Christian Gulseth, Sigbjørn Elle, Paal Dag Norheim, Armando A. Calvo Quiroz, Pastor A. Cesar Augusto, Manuel Gustavo León Portocarrero, Luis Fernando Vidal Neira, Jose Chavez, Boris Garro Barrera, Rita Kuroiwa Sampei, Bellatín V. Luis Fernando, Rogger Oquelis Cabredo, Sonia Castillo, Agustin Miguel G Morales, Perry Pua Tan, Liberato Antonio C Leagogo, Edward HM Wang, Julie T Li-Yu, Andrzej Z Sawicki, Barbara Stasiuk, Grzegorz Kania, Roman Lorenc, Anna Sidorowicz-Bialynicka, Leszek Szczepanski, Edward Franek, Rafal Filip, Jan Sekula, Tomasz Blicharski, Piotr Leszczynski, Ewa Sewerynek, Tomasz Miazgowski, Andrzej Milewicz, Magda Dabrowska, Jerzy Romaszko, Wojciech Pluskiewicz, Lukasz Wojnowski, Catalin Codreanu, Horatiu Bolosiu, Ruxandra Ionescu, Ioana Zosin, Liviu Macovei, Mihai Bojinca, Florin Radulescu, Simona Pop, Adrian Sarbu, Lidia I Benevolenskaya, Evgeny L Nasonov, Lyudmila Ya Rozhinskaya, Raphael G Oganov, Svetlana S Rodionova, Eugeny Vladimirovich Shlyakhto, Vasiliy Trofimov, Eugeny G Zotkin, Irina E Zazerskaya, Elena N Grineva, Olga Ershova, Olga Lesnyak, Olga D Ostroumova, Svetlana B Malichenko, Eduard G Pikhlak, Valery G Pilyaev, Tatiana Raskina, Elena V Zonova, Valery S Shirinsky, Aleksandar N Dimic, Goran Cobeljic, Svetlana Vujovic, Graham Charlston Ellis, Stanley Lipschitz, Tobias Johannes De Villiers, Albert Jan De Weerd, Tasneem Vally, Yvonne Trinder, Jacobus Ludewikus Coetsee, Charles Pierre Davis, Savithree Nayiager, Frans Stephanus Hough, Louis F Oelofse, Eugene van der Walt, Johannes Jurgens Lombaard, Suzanne Blignaut, Uttam Govind, Leon Frederik Fouche, Dawid Stephanus Kruger, Johannes Paul Dalmeyer, Mada M Ferreira, Alejandro Escudero-Contreras, Manuel Muñoz Torres, Federico Hawkins Carranza, Jose Luis Perez Castrillon, Juan Antonio García Meijide, Esteban Jodar Gimeno, Santiago Palacios Gil-Antuñana, Luis de Teresa Parreno, Emilio Martín Mola, Carmen Alvarez Sanchez, Keh-Sung Tsai, Shih-Te Tu, Jung-Fu Chen, Oscar Kuang-Sheng Lee, Wen-Wei Hsu, Natalia Viktorivna Grygorieva, Vladyslav Volodymyrovych Povoroznyuk, Mykola Oleksiiovych Korzh, Oleksandr Levgeniiovych Loskutov, Andriy Borysovych Chukov, Rex Sarmiento, Hawys Thomas, Hugh Donnachie, Irina Pavel-Knox, Hilary Shaw, Hana Hassanin, Essam Eldin Ahmed Abdulhakim, Naren Savani, Gloria A Bachmann, Elizabeth Barrett-Connor, Neil C Binkley, Henry G Bone, Donald M Brandon, Darin David Checketts, Neil J Fraser, Nelson B Watts, Steven A Geller, Joseph S Gimbel, Maria White Greenwald, Peter A Holt, Cyrus Conrad Johnston, Chien Fang, David J Klashman, E. Michael Lewiecki, Mitchell B Lowenstein, Michael Roy McClung, Susan M Nattrass, Alberto Odio, Julie Levengood, Josefina Romaguera, Mohamed Bassam Sebai, Brian Snyder, Mark Eliot Kutner, Dan Streja, Elliott P Schwartz, and Mark G Christiansen
Subjects: cathepsin-k inhibitor, Endocrinology, Diabetes and Metabolism, Osteoporosis, Placebo-controlled study, law.invention, Fractures, Bone, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Randomized controlled trial, Bone Density, law, Outpatient clinic, 030212 general & internal medicine, Osteoporosis, Postmenopausal, Aged, 80 and over, density, Hip fracture, Bone Density Conservation Agents, odanacatib, postmenopausal osteoporosis, LOFT, extension study, Treatment Outcome, medicine.anatomical_structure, Spinal Fractures, Female, women, strength, Odanacatib, medicine.medical_specialty, 030209 endocrinology & metabolism, Placebo, 03 medical and health sciences, Double-Blind Method, Internal medicine, Internal Medicine, medicine, Humans, bone mass, fracture, mortality, denosumab, turnover, therapy, Aged, Femoral neck, Hip Fractures, business.industry, Biphenyl Compounds, medicine.disease, chemistry, business, Osteoporotic Fractures
Abstract: Background: Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods: The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings: Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p
Published: 2019
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26. Correlation between kidney and peripheral nerve functions in Type 2 diabetes

Author: Chu-Hua Lu, Y R Lai, Chi-Ren Huang, Wen-Chan Chiu, Ben-Chung Cheng, Jung-Fu Chen, and N.-W. Tsai
Subjects: Adult, Male, medicine.medical_specialty, Urinalysis, Urology, Renal function, Type 2 diabetes, 030204 cardiovascular system & hematology, Kidney, Kidney Function Tests, Asymptomatic, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Diabetes mellitus, medicine, Humans, Diabetic Nephropathies, Peripheral Nerves, Prospective Studies, Prospective cohort study, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, General Medicine, Middle Aged, medicine.disease, Peripheral neuropathy, Diabetes Mellitus, Type 2, Linear Models, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Glomerular Filtration Rate, Retinopathy
Abstract: BackgroundAlthough greater impairments in nerve functions parameters are most likely to occur with a lower kidney function, there is a paucity of information on the relationship between the kidney and peripheral nerve functions parameters in Type 2 diabetes.AimTo address the impact of peripheral nerve functions in Type 2 diabetes patients in different stages of chronic kidney diseases (CKD).DesignThis prospective study enrolled 238 patients with Type 2 diabetes at a tertiary medical center.MethodWe designed composite amplitude scores of nerve conductions (CAS) as a measure of severity of peripheral neuropathy (PN), and used estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) parameters to stage CKD in Type 2 diabetes patients. The intrapersonal mean, standard deviation and coefficient of variation of eGFR for 238 patients were obtained in the 3 years prior to the study.ResultsThe patients who had lower eGFR and higher UACR were older, with longer diabetes duration, a greater percentage of retinopathy and PN and higher CAS. Multiple linear regression analysis revealed that diabetes duration and eGFR were independently associated with CAS, and a cut-off value of eGFR in the presence of PN was 65.3 ml/min/1.73 m2.ConclusionWe observed a close relationship between the severity of kidney and peripheral nerve function in patients with diabetes. If a patient’s eGFR value is below 65.3 ml/min/1.73 m2 or the UACR value is above 98.6 mg/dl, caution is needed with the presence of PN even in diabetic patients who are asymptomatic.
Published: 2019
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27. The role of bone mineral density in therapeutic decision-making using the Fracture Risk Assessment Tool (FRAX): a sub-study of the Taiwan OsteoPorosis Survey (TOPS)

Author: Shan Fu Yu, Wen Chan Chiu, Tien Tsai Cheng, Chih Hsing Wu, Chung-Yuan Hsu, Han Ming Lai, Jia Feng Chen, Ying Chou Chen, Yu-Jih Su, and Jung Fu Chen
Subjects: musculoskeletal diseases, 0301 basic medicine, Fracture risk, Adult, medicine.medical_specialty, FRAX, Younger age, Osteoporosis, Taiwan, 030209 endocrinology & metabolism, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Asian People, Bone Density, Risk Factors, Internal medicine, Surveys and Questionnaires, medicine, Humans, Orthopedics and Sports Medicine, Aged, Probability, Bone mineral, Aged, 80 and over, Hip fracture, business.industry, Hip Fractures, musculoskeletal, neural, and ocular physiology, Therapeutic decision making, Middle Aged, musculoskeletal system, medicine.disease, Orthopedic surgery, Female, 030101 anatomy & morphology, business, Algorithms, Osteoporotic Fractures
Abstract: Fracture Risk Assessment Tool (FRAX)–based intervention threshold (IT) is widely applied for treatment decision-making; however, an IT based on FRAX without the measurement of bone mass density (BMD) has not been validated. The study demonstrated that estimates of fracture risk by FRAX without BMD were higher than those by FRAX with BMD in women with old age. BMD is an integral component for bone strength assessment, but age-specific impacts of BMD on fracture risk assessment and therapeutic decision-making remained unclear. We aimed to investigate whether using BMD measurement changed the interpretation of the FRAX-based fracture probability assessment and treatment decision. The database was provided by the Taiwanese Osteoporosis Association (TOA) which conducted a nationwide survey of BMD. We calculated the 10-year major and hip fracture probabilities using the FRAX for each participant, either with (FRAX + BMD) or without BMD (FRAX − BMD). Age-specific individual intervention thresholds (IITs) were established using the FRAX-based fracture risk, equivalent to a woman with a prior fracture. Participants whose FRAX scores of major fracture were greater than or equal to their IITs were deemed suitable for therapeutic intervention. A total of 14,007 postmenopausal women were enrolled. Compared with FRAX + BMD, FRAX − BMD predicted lower FRAX scores in major and hip fractures in subjects aged 40–60 years; however, FRAX − BMD estimated higher risks for those aged 61–90 years. The therapeutic decision using FRAX − BMD was concordant to that using FRAX + BMD in 90.5% of the subjects, especially in the younger age group (40–70 years). FRAX − BMD identified more treatment candidates (7.7–16.4%) among those aged 71–90 years. The FRAX scores are influenced by age, irrespective of the consideration of BMD. FRAX − BMD is able to identify more subjects for therapeutic intervention in the elderly population. We should reconsider the role of BMD at different ages for therapeutic decision-making.
Published: 2019

28. HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration

Author: Yun-Ru Lai, Chih-Cheng Huang, Wen-Chan Chiu, Rue-Tsuan Liu, Nai-Wen Tsai, Hung-Chen Wang, Wei-Che Lin, Ben-Chung Cheng, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Pei-Wen Wang, Jung-Fu Chen, and Cheng-Hsien Lu
Subjects: medicine.medical_specialty, Longitudinal study, endocrine system diseases, Coefficient of variation, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, lcsh:RC321-571, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Linear regression, medicine, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Original Research, HbA1c variability, business.industry, General Neuroscience, nutritional and metabolic diseases, composite autonomic scoring scale, Stepwise regression, medicine.disease, long diabetes duration, chemistry, Cardiology, Glycated hemoglobin, type 2 diabetes, business, Retinopathy, Neuroscience, cardiovascular autonomic neuropathy
Abstract: Background Variability in the glycated hemoglobin (HbA1c) level is associated with a higher risk of microvascular complications in patients with type 2 diabetes. We tested the hypothesis that HbA1c variability is not only strongly associated with the presence but also the degree of severity of cardiovascular autonomic neuropathy (CAN) in patients with long diabetes durations (more than 10 years). Methods For each patient, the intrapersonal mean, standard deviation (SD), and coefficient of variation (CV) for HbA1c were calculated using all measurements obtained 3 years before the study. We constructed the composite autonomic scoring scale (CASS) as a measure of the severity of cardiovascular autonomic functions. Stepwise logistic regression and linear regression analyses were performed to evaluate the presence of CAN and the influence of independent variables on the mean CASS, respectively. Results Those with CAN had a higher mean age, a higher low-density lipoprotein cholesterol (LDL-C), HbA1c-SD, HbA1c-CV, mean HbA1c, and index HbA1c, higher prevalence of retinopathy as the underlying disease, and lower high-density lipoprotein (HDL) levels. Stepwise logistic regression showed that HbA1c-SD and retinopathy were risk factors that were independently associated with the presence of CAN. Mean HbA1c, HbA1c-CV, HbA1c-SD, and index HbA1c were positively correlated with mean CASS, and a multiple linear regression analysis revealed that HbA1c-SD was independently associated with the mean CASS. Conclusion HbA1c variability is strongly associated with not only the presence but also the degree of severity of CAN. A longitudinal study is required to confirm whether controlling blood glucose level is effective in reducing CAN progression.
Published: 2019

29. Novel algorithm generating strategy to identify high fracture risk population using a hybrid intervention threshold

Author: Jia Feng Chen, Wen Chan Chiu, Yu-Jih Su, Han Ming Lai, Chih Hsing Wu, Chi Hua Ko, Ying Chou Chen, Chung-Yuan Hsu, Jung Fu Chen, Shan Fu Yu, and Tien Tsai Cheng
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteoporosis, Population, Taiwan, 030209 endocrinology & metabolism, Group B, 03 medical and health sciences, Fractures, Bone, 0302 clinical medicine, Endocrinology, Bone Density, Risk Factors, medicine, Cutoff, Humans, Orthopedics and Sports Medicine, education, Femoral neck, Aged, Probability, Bone mineral, Hip fracture, education.field_of_study, business.industry, Hip Fractures, General Medicine, medicine.disease, medicine.anatomical_structure, Orthopedic surgery, Female, 030101 anatomy & morphology, business, Algorithm, Algorithms
Abstract: The aim of this study was to develop an algorithm to identify high-risk populations of fragility fractures in Taiwan. A total of 16,539 postmenopausal women and men (age ≥ 50 years) were identified from the Taiwan Osteoporosis Survey database. Using the Taiwan FRAX® tool, the 10-year probability of major osteoporotic fracture (MOF) and hip fracture (HF) and the individual intervention threshold (IIT) of each participant were calculated. Subjects with either a probability above the IIT or those with MOF ≥ 20% or HF ≥ 9% were included as group A. Subjects with a bone mineral density (BMD) T-score at femoral neck based on healthy subjects of ≤ − 2.5 were included in group B. We tested several cutoff points for MOF and HF so that the number of patients in group A and group B were similar. A novel country-specific hybrid intervention threshold along with an algorithm was generated to identify high fracture risk individuals. 3173 (19.2%) and 3129 (18.9%) participants were categorized to groups A and B, respectively. Participants in group B had a significantly lower BMD (p
Published: 2019

30. Prevalence of diabetic macrovascular complications and related factors from 2005 to 2014 in Taiwan: A nationwide survey

Author: Yi-Jen Hung, Yi-Ling Wu, Jung-Fu Chen, Ming-Chu Chin, Chien-Hsing Lee, and Jeng-Fu Kuo
Subjects: Adult, Male, medicine.medical_specialty, endocrine system diseases, Taiwan, Disease, Nationwide survey, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Age Distribution, Risk Factors, Diabetes mellitus, Internal medicine, Surveys and Questionnaires, Health care, medicine, Prevalence, Humans, In patient, cardiovascular diseases, Registries, Sex Distribution, Stroke, Aged, Related factors, Heart Failure, Peripheral Vascular Diseases, lcsh:R5-920, business.industry, General Medicine, Middle Aged, medicine.disease, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Diagnosis code, business, lcsh:Medicine (General)
Abstract: Background/Purpose: Diabetic macrovascular complications contribute to nonignorable causes of morbidity and mortality in patients with diabetes mellitus (DM). In this study, the trends of risk factors and macrovascular complications were examined in patients with DM in Taiwan. Methods: Health care information and International Classification of Diseases, Ninth Revision diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files between 2005 and 2014. Using these data, the number of cases and annual prevalence of diabetic macrovascular complications in individuals with DM were stratified by age and sex. Results: The prevalence of DM with either stroke or cardiovascular disease (CVD) showed a decreasing trend in enrolled patients with DM (p for trend
Published: 2019

31. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

Author: Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Fady T Botros, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev 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Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest
Subjects: Male, medicine.medical_specialty, medicine.medical_treatment, Recombinant Fusion Proteins, Placebo-controlled study, Glucagon-Like Peptides, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Albuminuria, Humans, Hypoglycemic Agents, Diabetic Nephropathies, 030212 general & internal medicine, Renal replacement therapy, Aged, Intention-to-treat analysis, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Diabetes Mellitus, Type 2, Creatinine, Dulaglutide, Female, business, medicine.drug, Kidney disease, Glomerular Filtration Rate
Abstract: Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud
Published: 2019

32. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

Author: Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Jeffrey S Riesmeyer, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev Esenyan, Ekaterina Gelig, Sergey Gilyarevsky, Maria Golshmid, Arseniy Goncharov, Anastasia Gorbunova, Ivan Gordeev, Vera Gorelysheva, Tatiana Goryunova, Irina Grebenshchikova, Roman Ilchenko, Maria Ivannikova, Saule Karabalieva, Juliya Karpeeva, Elena Khaykina, Zhanna Kobalava, Irina Kononenko, Oxana Korolik, Anna Korshunova, Victor Kostenko, Irina Krasnopevtseva, Ludmila Krylova, Polina Kulkova, Irina Kuzmina, Alla Ledyaeva, Sergey Levashov, Natalia Lokhovinina, Vadim Lvov, Narine Martirosyan, Sergey Nedogoda, Rostislav Nilk, Yulia Osmolovskaya, Alexey Panov, Olga Paramonova, Ekaterina Pavlova, Elena Pekareva, Nina Petunina, Svetlana Ponamareva, Galina Reshedko, Alla Salasyuk, Malvina Sepkhanyan, Alexandr Serebrov, Olesya Shabelnikova, Andrey Skvortsov, Olga Smirnova, Oxana Spiridonova, Svetlana Strogova, Evgeny Taratukhin, Sergey Tereschenko, Lubov Trukhina, Olga Tsarkova, Vera Tsoma, Farid Tumarov, Natalya Tyan, Tatiana Tyurina, Svetlana Villevalde, Elena Yankovaya, Ludmila Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest
Subjects: Male, medicine.medical_specialty, Recombinant Fusion Proteins, Population, Placebo-controlled study, Glucagon-Like Peptides, Myocardial Infarction, Type 2 diabetes, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, education, Aged, education.field_of_study, business.industry, Semaglutide, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Stroke, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Dulaglutide, Female, business, medicine.drug
Abstract: Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud
Published: 2019

33. Mitochondrial DNA variants as genetic risk factors for Parkinson disease

Author: Jiin-Haur Chuang, Jung-Fu Chen, Wen-Chin Lee, Chin-Song Lu, Chia-Wei Liou, Pei-Wen Wang, Mao-Meng Tiao, Sheng-Teng Huang, Shang-Der Chen, Rou-Shayn Chen, T. L. Huang, P. H. Huang, Tsu-Kung Lin, and Shao-Wen Weng
Subjects: Male, 0301 basic medicine, Mitochondrial DNA, Mitochondrion, DNA, Mitochondrial, Haplogroup, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Genetic variation, Humans, Medicine, Coding region, Aged, Genetics, business.industry, Haplotype, Genetic Variation, Parkinson Disease, Odds ratio, Middle Aged, 030104 developmental biology, Haplotypes, Neurology, Female, Neurology (clinical), business, 030217 neurology & neurosurgery, Human mitochondrial DNA haplogroup
Abstract: Background and purpose Investigation of the relationship between mitochondrial DNA (mtDNA) variants and Parkinson disease (PD) remains an issue awaiting more supportive evidence. Moreover, an affirming cellular model study is also lacking. Methods The index mtDNA variants and their defining mitochondrial haplogroup were determined in 725 PD patients and 744 non-PD controls. Full-length mtDNA sequences were also conducted in 110 cases harboring various haplogroups. Cybrid cellular models, composed by fusion of mitochondria-depleted rho-zero cells and donor mitochondria, were used for a rotenone-induced PD simulation study. Results Multivariate logistic regression analysis revealed that subjects harboring the mitochondrial haplogroup B5 have resistance against PD (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002). Furthermore, a composite mtDNA variant group consisting of A10398G and G8584A at the coding region was found to have resistance against PD (odds ratio 0.50, 95% confidence interval 0.33–0.78; P = 0.001). In cellular studies, B4 and B5 cybrids were selected according to their higher resistance to rotenone, in comparison with cybrids harboring other haplogroups. The B5 cybrid, containing G8584A/A10398G variants, showed more resistance to rotenone than the B4 cybrid not harboring these variants. This is supported by findings of low reactive oxygen species generation and a low apoptosis rate in the B5 cybrid, whereas a higher expression of autophagy was observed in the B4 cybrid particularly under medium dosage and longer treatment time with rotenone. Conclusions Our studies, offering positive results from clinical investigations and cybrid experiments, provide data supporting the role of variant mtDNA in the risk of PD.
Published: 2016
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34. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Author: Hiddo J L Heerspink, Hans-Henrik Parving, Dennis L Andress, George Bakris, Ricardo Correa-Rotter, Fan-Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John J V McMurray, Joel Z Melnick, Michael G Miller, Pablo E Pergola, Vlado Perkovic, Sheldon Tobe, Tingting Yi, Melissa Wigderson, Dick de Zeeuw, Alicia Elbert, Augusto Vallejos, Andres Alvarisqueta, Laura Maffei, Luis Juncos, Javier de Arteaga, Gustavo Greloni, Eduardo Farias, Alfredo Zucchini, Daniel Vogel, Ana Cusumano, Juan Santos, Margaret Fraenkel, Martin Gallagher, Tim Davis, Shamasunder Acharya, Duncan Cooke, Michael Suranyi, Simon Roger, Nigel Toussaint, Carol Pollock, Doris Chan, Stephen Stranks, Richard MacIsaac, Zoltan Endre, Alice Schmidt, Rudolf Prager, Gert Mayer, Xavier Warling, Michel Jadoul, Jean Hougardy, Chris Vercammen, Bruno Van Vlem, Pieter Gillard, Adriana Costa e Forti, Joao Lindolfo Borges, Luis Santos Canani, Freddy Eliaschewitz, Silmara Leite, Fadlo Fraige Filho, Raphael Paschoalin, Jose Andrade Moura Neto, Luciane Deboni, Irene de Lourdes Noronha, Cintia Cercato, Carlos Alberto Prompt, Maria Zanella, Nelson Rassi, Domingos D'Avila, Rosangela Milagres, Joao Felicio, Roberto Pecoits Filho, Miguel Carlos Riella, Joao Salles, Elizete Keitel, Sergio Draibe, Celso Amodeo, Joseph Youmbissi, Louise Roy, Serge Cournoyer, Shivinder Jolly, Vincent Pichette, Gihad Nesrallah, Harpreet Singh Bajaj, Hasnain Khandwala, Ronnie Aronson, Richard Goluch, Paul Tam, Christian Rabbat, Gordon Bailey, Stephen Chow, Alvaro Castillo, Alfredo Danin Vargas, Fernando Gonzalez, Rodrigo Munoz, Vicente Gutierrez, Gonzalo Godoy, Hongwen Zhao, Zhangsuo Liu, Minghui Zhao, Xiaohui Guo, Benli Su, Shuxia Fu, Yan Xu, Jinkui Yang, Bingyin Shi, Guanqing Xiao, Wei Shi, Chuanming Hao, Changying Xing, Fanfan Hou, Qun Luo, Yuxiu Li, Linong Ji, Li Zuo, Song Wang, Zhaohui Ni, Guohua Ding, Nan Chen, Jiajun Zhao, Weiping Jia, Shengqiang Yu, Jian Weng, Gang Xu, Ping Fu, Shiren Sun, Bicheng Liu, Xiaoqiang Ding, Ivan Rychlik, Alexandra Oplustilova, Dagmar Bartaskova, Vaclava Honova, Hana Chmelickova, Martin Petr, Petr Bucek, Vladimir Tesar, Emil Zahumensky, Johan Povlsen, Kenneth Egstrup, Anna Oczachowska-Kulik, Peter Rossing, Jorma Lahtela, Jorma Strand, Ilkka Kantola, Catherine Petit, Christian Combe, Philippe Zaoui, Vincent Esnault, Pablo Urena Torres, Jean-Michel Halimi, Bertrand Dussol, Tasso Bieler, Klemens Budde, Frank Dellanna, Thomas Segiet, Christine Kosch, Hans Schmidt-Guertler, Isabelle Schenkenberger, Volker Vielhauer, Frank Pistrosch, Mark Alscher, Christoph Hasslacher, Christian Hugo, Anja Muehlfeld, Christoph Wanner, Ploumis Passadakis, Theofanis Apostolou, Nikolaos Tentolouris, Ioannis Stefanidis, Konstantinos Mavromatidis, Vasilios Liakopoulos, Dimitrios Goumenos, Konstantinos Siamopoulos, Vincent Yeung, Risa Ozaki, Samuel Fung, Kathryn Tan, Sydney Tang, Sing Leung Lui, Siu Fai Cheung, Seamus Sreenan, Joseph Eustace, Donal O'Shea, Peter Lavin, Austin Stack, Yoram Yagil, Julio Wainstein, Hilla Knobler, Josef Cohen, Irina Kenis, Deeb Daoud, Yosefa Bar-Dayan, Victor Frajewicki, Faiad Adawi, Loreto Gesualdo, Domenico Santoro, Francesco Marino, Andrea Galfre, Chiara Brunati, Piero Ruggenenti, Giuseppe Rombola, Giuseppe Pugliese, Maura Ravera, Fabio Malberti, Giuseppe Pontoriero, Teresa Rampino, Salvatore De Cosmo, Ciro Esposito, Felice Nappi, Cataldo Abaterusso, Giuseppe Conte, Vincenzo Panichi, Davide Lauro, Giovambattista Capasso, Domenico Russo, Jiichi Anzai, Motoji Naka, Keita Ato, Tetsuro Tsujimoto, Toshinori Nimura, Eitaro Nakashima, Tetsuro Takeda, Shinya Fujii, Kunihisa Kobayashi, Hideaki Iwaoka, Koji Nagayama, Hiroyuki Harada, Hajime Maeda, Rui Kishimoto, Tadashi Iitsuka, Naoki Itabashi, Ryuichi Furuya, Yoshitaka Maeda, Daishiro Yamada, Nobuhiro Sasaki, Hiromitsu Sasaki, Shinichiro Ueda, Naoki Kashihara, Shuichi Watanabe, Takehiro Nakamura, Hidetoshi Kanai, Yuichiro Makita, Keiko Ono, Noriyuki Iehara, Daisuke Goto, Keiichiro Kosuge, Kenichi Tsuchida, Toshiaki Sato, Takashi Sekikawa, Hideki Okamoto, Tsuyoshi Tanaka, Naoko Ikeda, Takenobu Tadika, Koji Mukasa, Takeshi Osonoi, Fuminori Hirano, Motonobu Nishimura, Yuko Yambe, Yukio Tanaka, Makoto Ujihara, Takashi Sakai, Mitsuo Imura, Yutaka Umayahara, Shinya Makino, Jun Nakazawa, Yukinari Yamaguchi, Susumu Kashine, Hiroaki Miyaoka, Katsunori Suzuki, Toshihiko Inoue, Sou Nagai, Nobuyuki Sato, Masahiro Yamamoto, Noriyasu Taya, Akira Fujita, Akira Matsutani, Yugo Shibagaki, Yuichi Sato, Akira Yamauchi, Masahiro Tsutsui, Tamayo Ishiko, Shizuka Kaneko, Nobuyuki Azuma, Hirofumi Matsuda, Yasuhiro Hashiguchi, Yukiko Onishi, Mikiya Tokui, Munehide Matsuhisa, Arihiro Kiyosue, Junji Shinoda, Kazuo Ishikawa, Ghazali Ahmad, Shalini Vijayasingham, Nor Azizah Aziz, Zanariah Hussein, Yin Khet Fung, Wan Hasnul Halimi Wan Hassan, Hin Seng Wong, Bak Leong Goh, Norhaliza Mohd Ali, Nor Shaffinaz Yusuf Azmi Merican, Indralingam Vaithilingam, Nik Nur Fatnoon Nik Ahmad, Noor Adam, Norlela Sukor, V Paranthaman P Vengadasalam, Khalid Abdul Kadir, Mafauzy Mohamed, Karina Renoirte Lopez, Aniceto Leguizamo-Dimas, Alfredo Chew Wong, Jose Chevaile-Ramos, Jose Gonzalez Gonzalez, Raul Rico Hernandez, Jose Nino-Cruz, Leobardo Sauque Reyna, Guillermo Gonzalez-Galvez, Magdalena Madero Rovalo, Tomasso Bochicchio-Ricardelli, Jorge Aldrete, Jaime Carranza-Madrigal, Liffert Vogt, Peter Smak Gregoor, JNM Barendregt, Peter Luik, Ronald Gansevoort, Gozewijn Laverman, Helen Pilmore, Helen Lunt, John Baker, Steven Miller, Kannaiyan Rabindranath, Luis Zapata-Rincon, Rolando Vargas-Gonzales, Jorge Calderon Ticona, Augusto Dextre Espinoza, Jose Burga Nunez, Carlos Antonio Zea-Nunez, Benjamin Herrada Orue, Boris Medina-Santander, Cesar Delgado-Butron, Julio Farfan-Aspilcueta, Stanislaw Mazur, Miroslaw Necki, Michal Wruk, Katarzyna Klodawska, Grazyna Popenda, Ewa Skokowska, Malgorzata Arciszewska, Andrzej Wiecek, Kazimierz Ciechanowski, Michal Nowicki, Rita Birne, Antonio Cabrita, Aura Ramos, Manuel Anibal Antunes Ferreira, Evelyn Matta Fontanet, Altagracia Aurora Alcantara-Gonzalez, Angel Comulada-Rivera, Eugenia Galindo Ramos, Jose Cangiano, Luis Quesada-Suarez, Ricardo Calderon Ortiz, Jose Vazquez-Tanus, Rafael Burgos-Calderon, Carlos Rosado, Nicolae Hancu, Ella Pintilei, Cristina Mistodie, Gabriel Bako, Lavinia Ionutiu, Ligia Petrica, Romulus Timar, Liliana Tuta, Livia Duma, Adriana Tutescu, Svetlana Ivanova, Ashot Essaian, Konstantin Zrazhevskiy, Natalia Tomilina, Elena Smolyarchuk, Anatoly Kuzin, Olga Lantseva, Irina Karpova, Minara Shamkhalova, Natalia Liberanskaya, Andrey Yavdosyuk, Yuri Shvarts, Tatiana Bardymova, Olga Blagoveshchenskaya, Oleg Solovev, Elena Rechkova, Natalia Pikalova, Maria Pavlova, Elena Kolmakova, Rustam Sayfutdinov, Svetlana Villevalde, Natalya Koziolova, Vladimir Martynenko, Vyacheslav Marasaev, Adelya Maksudova, Olga Sigitova, Viktor Mordovin, Vadim Klimontov, Yulia Samoylova, Tatiana Karonova, Lee Ying Yeoh, Boon Wee Teo, Marjorie Wai Yin Foo, Adrian Liew, Ivan Tkac, Aniko Oroszova, Jozef Fekete, Jaroslav Rosenberger, Ida Obetkova, Alla Fulopova, Eva Kolesarova, Katarina Raslova, Peter Smolko, Adrian Oksa, Larry Distiller, Julien Trokis, Luthando Adams, Hemant Makan, Padaruth Ramlachan, Essack Mitha, Kathleen Coetzee, Zelda Punt, Qasim Bhorat, Puvenesvari Naiker, Graham Ellis, Louis Van Zyl, Kwan Woo Lee, Min Seon Kim, Soon-Jib Yoo, Kun Ho Yoon, Yong-Wook Cho, Tae-Sun Park, Sang Yong Kim, Moon-Gi Choi, Tae Keun Oh, Kang-Wook Lee, Ho Sang Shon, Sung Hwan Suh, Byung-Joon Kim, Kim Doo-Man, Joo Hark Yi, Sang Ah Lee, Ho Chan Cho, Sin-Gon Kim, Dae-Ryong Cha, Ji A Seo, Kyung Mook Choi, Jeong-Taek Woo, Kyu Jeung Ahn, Jae Hyuk Lee, In-Joo Kim, Moon-Kyu Lee, Hak Chul Jang, Kyong-Soo Park, Beom Seok Kim, Ji Oh Mok, Mijung Shin, Sun Ae Yoon, Il-Seong Nam-Goong, Choon Hee Chung, Tae Yang Yu, Hyoung Woo Lee, Alfonso Soto Gonzalez, Jaume Almirall, Jesus Egido, Francesca Calero Gonzalez, Gema Fernandez Fresnedo, Ildefonso Valera Cortes, Manuel Praga Terente, Isabel Garcia Mendez, Juan Navarro Gonzalez, Jose Herrero Calvo, Secundino Cigarran Guldris, Mario Prieto Velasco, Jose Ignacio Minguela Pesquera, Antonio Galan, Julio Pascual, Maria Marques Vidas, Judith Martins Munoz, Jose Rodriguez-Perez, Cristina Castro-Alonso, Josep Bonet Sol, Daniel Seron, Elvira Fernandez Giraldez, Javier Arrieta Lezama, Nuria Montero, Julio Hernandez-Jaras, Rafael Santamaria Olmo, Jose Ramon Molas Coten, Olof Hellberg, Bengt Fellstrom, Andreas Bock, Dee Pei, Ching-Ling Lin, Kai-Jen Tien, Ching-Chu Chen, Chien-Ning Huang, Ju-Ying Jiang, Du-An Wu, Chih-Hsun Chu, Shih-Ting Tseng, Jung-Fu Chen, Cho-Tsan Bau, Wayne Sheu, Mai-Szu Wu, Ramazan Sari, Siren Sezer, Alaattin Yildiz, Ilhan Satman, Betul Kalender, Borys Mankovskyy, Ivan Fushtey, Mykola Stanislavchuk, Mykola Kolenyk, Iryna Dudar, Viktoriia Zolotaikina, Orest Abrahamovych, Tetyana Kostynenko, Olena Petrosyan, Petro Kuskalo, Olga Galushchak, Oleg Legun, Ivan Topchii, Liliya Martynyuk, Vasyl Stryzhak, Svitlana Panina, Sergii Tkach, Vadym Korpachev, Peter Maxwell, Luigi Gnudi, Sui Phin Kon, Hilary Tindall, Phillip Kalra, Patrick Mark, Dipesh Patel, Mohamed El-Shahawy, Liqun Bai, Romanita Nica, Yeong-Hau Lien, Judson Menefee, Robert Busch, Alan Miller, Azazuddin Ahmed, Ahmed Arif, Joseph Lee, Sachin Desai, Shweta Bansal, Marie Bentsianov, Mario Belledonne, Charles Jere, Raul Gaona, Gregory Greenwood, Osvaldo Brusco, Mark Boiskin, Diogo Belo, Raffi Minasian, Naveen Atray, Mary Lawrence, John Taliercio, Pablo Pergola, David Scott, German Alvarez, Bradley Marder, Thomas Powell, Wa'el Bakdash, George Stoica, Christopher McFadden, Marc Rendell, Jonathan Wise, Audrey Jones, Michael Jardula, Ivy-Joan Madu, Freemu Varghese, Brian Tulloch, Ziauddin Ahmed, Melanie Hames, Imran Nazeer, Newman Shahid, Rekha John, Manuel Montero, David Fitz-Patrick, Lawrence Phillips, Antonio Guasch, Elena Christofides, Aijaz Gundroo, Mohammad Amin, Cynthia Bowman-Stroud, Michael Link, Laura Mulloy, Michael Nammour, Tarik Lalwani, Lenita Hanson, Adam Whaley-Connell, Lee Herman, Rupi Chatha, Sayed Osama, Kenneth Liss, Zeid Kayali, Anuj Bhargava, Ezra Israel, Alfredo Peguero-Rivera, Michael Fang, Judith Slover, Elena Barengolts, Jose Flores, Rosemary Muoneke, Virginia Savin, Stella Awua-Larbi, Andrew Levine, George Newman, Laden Golestaneh, Guillermo Bohm, Efrain Reisin, Lucita Cruz, Robert Weiss, Franklin Zieve, Edward Horwitz, Peale Chuang, James Mersey, John Manley, Ronald Graf, Fadi Bedros, Sudhir Joshi, Juan Frias, Ali Assefi, Andrew O'Shaughnessy, Roman Brantley, Todd Minga, David Tietjen, Samuel Kantor, Aamir Jamal, Ramon Guadiz, Kenneth Hershon, Peter Bressler, Nelson Kopyt, Harold Cathcart, Scott Bloom, Ronald Reichel, Samer Nakhle, Emily Dulude, Joshua Tarkan, Penelope Baker, Steven Zeig, Jaynier Moya Hechevarria, Armando Ropero-Cartier, Gilda De la Calle, Ankur Doshi, Fadi Saba, Teresa Sligh, Sylvia Shaw, Jayant Kumar, Harold Szerlip, George Bayliss, Alan Perlman, Lakhi Sakhrani, Steven Gouge, Georges Argoud, Idalia Acosta, John Elder, Sucharit Joshi, John Sensenbrenner, Steven Vicks, Roberto Mangoo-Karim, Claude Galphin, Carlos Leon-Forero, John Gilbert, Eric Brown, Adeel Ijaz, Salman Butt, Mariana Markell, Carlos Arauz-Pacheco, Lance Sloan, Odilon Alvarado, Serge Jabbour, Eric Simon, Anjay Rastogi, Sam James, Karen Hall, John Melish, Brad Dixon, Allen Adolphe, Csaba Kovesdy, Srinivasan Beddhu, Richard Solomon, Ronald Fernando, Ellis Levin, Charuhas Thakar, Brooks Robey, David Goldfarb, Linda Fried, Geetha Maddukuri, Stephen Thomson, Andrew Annand, Saeed Kronfli, Paramjit Kalirao, Rebecca Schmidt, Neera Dahl, Samuel Blumenthal, Debra Weinstein, Ove Ostergaard, Talia Weinstein, Yasuhiro Ono, Murat Yalcin, Shahana Karim, APH - Health Behaviors & Chronic Diseases, Nephrology, ACS - Amsterdam Cardiovascular Sciences, ACS - Microcirculation, Biomedical Signals and Systems, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Heerspink, H. J. L., Parving, H. -H., Andress, D. L., Bakris, G., Correa-Rotter, R., Hou, F. -F., Kitzman, D. W., Kohan, D., Makino, H., Mcmurray, J. J. V., Melnick, J. Z., Miller, M. G., Pergola, P. E., Perkovic, V., Tobe, S., Yi, T., Wigderson, M., de Zeeuw, D., Elbert, A., Vallejos, A., Alvarisqueta, A., Maffei, L., Juncos, L., de Arteaga, J., Greloni, G., Farias, E., Zucchini, A., Vogel, D., Cusumano, A., Santos, J., Fraenkel, M., Gallagher, M., Davis, T., Acharya, S., Cooke, D., Suranyi, M., Roger, S., Toussaint, N., Pollock, C., Chan, D., Stranks, S., Macisaac, R., Endre, Z., Schmidt, A., Prager, R., Mayer, G., Warling, X., Jadoul, M., Hougardy, J., Vercammen, C., Van Vlem, B., Gillard, P., Costa e Forti, A., Borges, J. L., Santos Canani, L., Eliaschewitz, F., Leite, S., Fraige Filho, F., Paschoalin, R., Moura Neto, J. A., Deboni, L., de Lourdes Noronha, I., Cercato, C., Prompt, C. A., Zanella, M., Rassi, N., D'Avila, D., Milagres, R., Felicio, J., Pecoits Filho, R., Riella, M. C., Salles, J., Keitel, E., Draibe, S., Amodeo, C., Youmbissi, J., Roy, L., Cournoyer, S., Jolly, S., Pichette, V., Nesrallah, G., Bajaj, H. S., Khandwala, H., Aronson, R., Goluch, R., Tam, P., Rabbat, C., Bailey, G., Chow, S., Castillo, A., Danin Vargas, A., Gonzalez, F., Munoz, R., Gutierrez, V., Godoy, G., Zhao, H., Liu, Z., Zhao, M., Guo, X., Su, B., Fu, S., Xu, Y., Yang, J., Shi, B., Xiao, G., Shi, W., Hao, C., Xing, C., Hou, F., Luo, Q., Li, Y., Ji, L., Zuo, L., Wang, S., Ni, Z., Ding, G., Chen, N., Zhao, J., Jia, W., Yu, S., Weng, J., Xu, G., Fu, P., Sun, S., Liu, B., Ding, X., Rychlik, I., Oplustilova, A., Bartaskova, D., Honova, V., Chmelickova, H., Petr, M., Bucek, P., Tesar, V., Zahumensky, E., Povlsen, J., Egstrup, K., Oczachowska-Kulik, A., Rossing, P., Lahtela, J., Strand, J., Kantola, I., Petit, C., Combe, C., Zaoui, P., Esnault, V., Urena Torres, P., Halimi, J. -M., Dussol, B., Bieler, T., Budde, K., Dellanna, F., Segiet, T., Kosch, C., Schmidt-Guertler, H., Schenkenberger, I., Vielhauer, V., Pistrosch, F., Alscher, M., Hasslacher, C., Hugo, C., Muehlfeld, A., Wanner, C., Passadakis, P., Apostolou, T., Tentolouris, N., Stefanidis, I., Mavromatidis, K., Liakopoulos, V., Goumenos, D., Siamopoulos, K., Yeung, V., Ozaki, R., Fung, S., Tan, K., Tang, S., Lui, S. L., Cheung, S. F., Sreenan, S., Eustace, J., O'Shea, D., Lavin, P., Stack, A., Yagil, Y., Wainstein, J., Knobler, H., Cohen, J., Kenis, I., Daoud, D., Bar-Dayan, Y., Frajewicki, V., Adawi, F., Gesualdo, L., Santoro, D., Marino, F., Galfre, A., Brunati, C., Ruggenenti, P., Rombola, G., Pugliese, G., Ravera, M., Malberti, F., Pontoriero, G., Rampino, T., De Cosmo, S., Esposito, C., Nappi, F., Abaterusso, C., Conte, G., Panichi, V., Lauro, D., Capasso, G., Russo, D., Anzai, J., Naka, M., Ato, K., Tsujimoto, T., Nimura, T., Nakashima, E., Takeda, T., Fujii, S., Kobayashi, K., Iwaoka, H., Nagayama, K., Harada, H., Maeda, H., Kishimoto, R., Iitsuka, T., Itabashi, N., Furuya, R., Maeda, Y., Yamada, D., Sasaki, N., Sasaki, H., Ueda, S., Kashihara, N., Watanabe, S., Nakamura, T., Kanai, H., Makita, Y., Ono, K., Iehara, N., Goto, D., Kosuge, K., Tsuchida, K., Sato, T., Sekikawa, T., Okamoto, H., Tanaka, T., Ikeda, N., Tadika, T., Mukasa, K., Osonoi, T., Hirano, F., Nishimura, M., Yambe, Y., Tanaka, Y., Ujihara, M., Sakai, T., Imura, M., Umayahara, Y., Makino, S., Nakazawa, J., Yamaguchi, Y., Kashine, S., Miyaoka, H., Suzuki, K., Inoue, T., Nagai, S., Sato, N., Yamamoto, M., Taya, N., Fujita, A., Matsutani, A., Shibagaki, Y., Sato, Y., Yamauchi, A., Tsutsui, M., Ishiko, T., Kaneko, S., Azuma, N., Matsuda, H., Hashiguchi, Y., Onishi, Y., Tokui, M., Matsuhisa, M., Kiyosue, A., Shinoda, J., Ishikawa, K., Ahmad, G., Vijayasingham, S., Aziz, N. A., Hussein, Z., Fung, Y. K., Hassan, W. H. H. W., Wong, H. S., Goh, B. L., Ali, N. M., Merican, N. S. Y. A., Vaithilingam, I., Nik Ahmad, N. N. F., Adam, N., Sukor, N., Vengadasalam, V. P. P., Abdul Kadir, K., Mohamed, M., Renoirte Lopez, K., Leguizamo-Dimas, A., Chew Wong, A., Chevaile-Ramos, J., Gonzalez Gonzalez, J., Rico Hernandez, R., Nino-Cruz, J., Sauque Reyna, L., Gonzalez-Galvez, G., Madero Rovalo, M., Bochicchio-Ricardelli, T., Aldrete, J., Carranza-Madrigal, J., Vogt, L., Smak Gregoor, P., Barendregt, J. N. M., Luik, P., Gansevoort, R., Laverman, G., Pilmore, H., Lunt, H., Baker, J., Miller, S., Rabindranath, K., Zapata-Rincon, L., Vargas-Gonzales, R., Calderon Ticona, J., Dextre Espinoza, A., Burga Nunez, J., Zea-Nunez, C. A., Herrada Orue, B., Medina-Santander, B., Delgado-Butron, C., Farfan-Aspilcueta, J., Mazur, S., Necki, M., Wruk, M., Klodawska, K., Popenda, G., Skokowska, E., Arciszewska, M., Wiecek, A., Ciechanowski, K., Nowicki, M., Birne, R., Cabrita, A., Ramos, A., Antunes Ferreira, M. A., Matta Fontanet, E., Alcantara-Gonzalez, A. A., Comulada-Rivera, A., Galindo Ramos, E., Cangiano, J., Quesada-Suarez, L., Calderon Ortiz, R., Vazquez-Tanus, J., Burgos-Calderon, R., Rosado, C., Hancu, N., Pintilei, E., Mistodie, C., Bako, G., Ionutiu, L., Petrica, L., Timar, R., Tuta, L., Duma, L., Tutescu, A., Ivanova, S., Essaian, A., Zrazhevskiy, K., Tomilina, N., Smolyarchuk, E., Kuzin, A., Lantseva, O., Karpova, I., Shamkhalova, M., Liberanskaya, N., Yavdosyuk, A., Shvarts, Y., Bardymova, T., Blagoveshchenskaya, O., Solovev, O., Rechkova, E., Pikalova, N., Pavlova, M., Kolmakova, E., Sayfutdinov, R., Villevalde, S., Koziolova, N., Martynenko, V., Marasaev, V., Maksudova, A., Sigitova, O., Mordovin, V., Klimontov, V., Samoylova, Y., Karonova, T., Yeoh, L. Y., Teo, B. W., Foo, M. W. Y., Liew, A., Tkac, I., Oroszova, A., Fekete, J., Rosenberger, J., Obetkova, I., Fulopova, A., Kolesarova, E., Raslova, K., Smolko, P., Oksa, A., Distiller, L., Trokis, J., Adams, L., Makan, H., Ramlachan, P., Mitha, E., Coetzee, K., Punt, Z., Bhorat, Q., Naiker, P., Ellis, G., Van Zyl, L., Lee, K. W., Kim, M. S., Yoo, S. -J., Yoon, K. H., Cho, Y. -W., Park, T. -S., Kim, S. Y., Choi, M. -G., Oh, T. K., Lee, K. -W., Shon, H. S., Suh, S. H., Kim, B. -J., Doo-Man, K., Yi, J. H., Lee, S. A., Cho, H. C., Kim, S. -G., Cha, D. -R., Seo, J. A., Choi, K. M., Woo, J. -T., Ahn, K. J., Lee, J. H., Kim, I. -J., Lee, M. -K., Jang, H. C., Park, K. -S., Kim, B. S., Mok, J. O., Shin, M., Yoon, S. A., Nam-Goong, I. -S., Chung, C. H., Yu, T. Y., Lee, H. W., Soto Gonzalez, A., Almirall, J., Egido, J., Calero Gonzalez, F., Fernandez Fresnedo, G., Valera Cortes, I., Praga Terente, M., Garcia Mendez, I., Navarro Gonzalez, J., Herrero Calvo, J., Cigarran Guldris, S., Prieto Velasco, M., Minguela Pesquera, J. I., Galan, A., Pascual, J., Marques Vidas, M., Martins Munoz, J., Rodriguez-Perez, J., Castro-Alonso, C., Bonet Sol, J., Seron, D., Fernandez Giraldez, E., Arrieta Lezama, J., Montero, N., Hernandez-Jaras, J., Santamaria Olmo, R., Molas Coten, J. R., Hellberg, O., Fellstrom, B., Bock, A., Pei, D., Lin, C. -L., Tien, K. -J., Chen, C. -C., Huang, C. -N., Jiang, J. -Y., Wu, D. -A., Chu, C. -H., Tseng, S. -T., Chen, J. -F., Bau, C. -T., Sheu, W., Wu, M. -S., Sari, R., Sezer, S., Yildiz, A., Satman, I., Kalender, B., Mankovskyy, B., Fushtey, I., Stanislavchuk, M., Kolenyk, M., Dudar, I., Zolotaikina, V., Abrahamovych, O., Kostynenko, T., Petrosyan, O., Kuskalo, P., Galushchak, O., Legun, O., Topchii, I., Martynyuk, L., Stryzhak, V., Panina, S., Tkach, S., Korpachev, V., Maxwell, P., Gnudi, L., Kon, S. P., Tindall, H., Kalra, P., Mark, P., Patel, D., El-Shahawy, M., Bai, L., Nica, R., Lien, Y. -H., Menefee, J., Busch, R., Miller, A., Ahmed, A., Arif, A., Lee, J., Desai, S., Bansal, S., Bentsianov, M., Belledonne, M., Jere, C., Gaona, R., Greenwood, G., Brusco, O., Boiskin, M., Belo, D., Minasian, R., Atray, N., Lawrence, M., Taliercio, J., Pergola, P., Scott, D., Alvarez, G., Marder, B., Powell, T., Bakdash, W., Stoica, G., Mcfadden, C., Rendell, M., Wise, J., Jones, A., Jardula, M., Madu, I. -J., Varghese, F., Tulloch, B., Ahmed, Z., Hames, M., Nazeer, I., Shahid, N., John, R., Montero, M., Fitz-Patrick, D., Phillips, L., Guasch, A., Christofides, E., Gundroo, A., Amin, M., Bowman-Stroud, C., Link, M., Mulloy, L., Nammour, M., Lalwani, T., Hanson, L., Whaley-Connell, A., Herman, L., Chatha, R., Osama, S., Liss, K., Kayali, Z., Bhargava, A., Israel, E., Peguero-Rivera, A., Fang, M., Slover, J., Barengolts, E., Flores, J., Muoneke, R., Savin, V., Awua-Larbi, S., Levine, A., Newman, G., Golestaneh, L., Bohm, G., Reisin, E., Cruz, L., Weiss, R., Zieve, F., Horwitz, E., Chuang, P., Mersey, J., Manley, J., Graf, R., Bedros, F., Joshi, S., Frias, J., Assefi, A., O'Shaughnessy, A., Brantley, R., Minga, T., Tietjen, D., Kantor, S., Jamal, A., Guadiz, R., Hershon, K., Bressler, P., Kopyt, N., Cathcart, H., Bloom, S., Reichel, R., Nakhle, S., Dulude, E., Tarkan, J., Baker, P., Zeig, S., Moya Hechevarria, J., Ropero-Cartier, A., De la Calle, G., Doshi, A., Saba, F., Sligh, T., Shaw, S., Kumar, J., Szerlip, H., Bayliss, G., Perlman, A., Sakhrani, L., Gouge, S., Argoud, G., Acosta, I., Elder, J., Sensenbrenner, J., Vicks, S., Mangoo-Karim, R., Galphin, C., Leon-Forero, C., Gilbert, J., Brown, E., Ijaz, A., Butt, S., Markell, M., Arauz-Pacheco, C., Sloan, L., Alvarado, O., Jabbour, S., Simon, E., Rastogi, A., James, S., Hall, K., Melish, J., Dixon, B., Adolphe, A., Kovesdy, C., Beddhu, S., Solomon, R., Fernando, R., Levin, E., Thakar, C., Robey, B., Goldfarb, D., Fried, L., Maddukuri, G., Thomson, S., Annand, A., Kronfli, S., Kalirao, P., Schmidt, R., Dahl, N., Blumenthal, S., Weinstein, D., Ostergaard, O., Weinstein, T., Ono, Y., Yalcin, M., Karim, S., Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
Subjects: Male, endothelin, albuminuria, nephropathy, inhibition, Diabetes Mellitus, Type 2/drug therapy, Endocrinology, Diabetes and Metabolism, Placebo-controlled study, Administration, Oral, 030204 cardiovascular system & hematology, Settore MED/13 - Endocrinologia, chemistry.chemical_compound, 0302 clinical medicine, ENDOTHELIN, 80 and over, Diabetic Nephropathies, 030212 general & internal medicine, Renal Insufficiency, Chronic, Aged, 80 and over, Diabetic Nephropathies/blood, General Medicine, Middle Aged, Atrasentan/administration & dosage, Editorial Commentary, Treatment Outcome, Nephrology, Creatinine, Administration, young adult, Female, medicine.symptom, Glomerular filtration rate, Type 2, Endothelin A Receptor Antagonists/administration & dosage, medicine.drug, Glomerular Filtration Rate, Human, Oral, Adult, medicine.medical_specialty, ALBUMINURIA, Endothelin A Receptor Antagonists, NEPHROPATHY, Urology, INHIBITION, Renal function, Serum Albumin, Human, Placebo, Nephropathy, 03 medical and health sciences, Young Adult, Double-Blind Method, Atresentan, diabetes, chronic kidney disease, medicine, Diabetes Mellitus, Aged, Atrasentan, Diabetes Mellitus, Type 2, Humans, Renal Insufficiency, Chronic, Serum Albumin, business.industry, Creatinine/blood, medicine.disease, Serum Albumin, Human/urine, n/a OA procedure, chemistry, Albuminuria, Renal Insufficiency, Chronic/blood, business, aged, 80 and over, Kidney disease
Abstract: Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
Published: 2019
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35. Close relationship between cardiovagal function and sural sensory nerve action potential in type 2 diabetes

Author: Jung-Fu Chen, Rue-Tsuan Liu, Chih-Min Su, Hung-Chen Wang, Ben-Chung Cheng, Wen-Chan Chiu, Yu-Jih Su, Nai-Wen Tsai, Sheng-Yuan Hsiao, Wei-Che Lin, Yun-Ru Lai, Jih-Yang Ko, Cheng-Hsien Lu, Chih-Cheng Huang, and Pei-Wen Wang
Subjects: Male, Vagus Nerve Diseases, medicine.medical_specialty, Time Factors, Neural Conduction, Diaphragmatic breathing, Action Potentials, Type 2 diabetes, Baroreflex, Sensitivity and Specificity, 050105 experimental psychology, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Sural Nerve, Heart Rate, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Humans, 0501 psychology and cognitive sciences, Aged, business.industry, 05 social sciences, Snap, Heart, Middle Aged, medicine.disease, Sensory Systems, nervous system, Neurology, Autonomic Nervous System Diseases, Diabetes Mellitus, Type 2, Close relationship, Area Under Curve, Cardiology, Sensory nerve action potential, Female, Neurology (clinical), business, Polyneuropathy, 030217 neurology & neurosurgery
Abstract: Objective Both diabetic distal symmetrical polyneuropathy (DSPN) and cardiac autonomic neuropathy (CAN) indicate the length-dependent pattern of disease. Decreased parasympathetic activity has been found in the early phase of CAN and sural sensory nerve action potential (SNAP) imply axonal loss in DSPN. Method All patients with type 2 diabetes underwent cardiovascular autonomic function and nerve conduction studies (NCS). We constructed modified composite autonomic scoring scale (CASS) and composite score of NCS to measure the severity of CAN and DSPN, respectively. Results Patients with a longer duration of diabetes had a lower heart rate response to deep breathing (HR_DB), Valsalva ratio (VR), and baroreflex sensitivity (BRS), higher CASS, a higher percentage of CAN, lower sural SNAP, higher composite score of NCS, and a higher percentage of DSPN. Multiple linear regression analysis showed that only sural SNAPs were independently associated with mean HR_DB. Conclusion Sural SNAP was closely correlated with parameters of cardiovagal functions in patients with different durations of diabetes. The percentage and severity of CAN and DSPN increase with longer duration of diabetes. Significance The independent association of sural sensory nerve action potential amplitude and heart rate response to deep breathing with type 2 diabetes is important because combined testing increases diagnostic sensitivity and specificity.
Published: 2018

36. Correction to: Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region

Author: Tang Ching Lau, Peter R. Ebeling, Paul Mitchell, Yin Fan Chang, Joon Kiong Lee, Fen Lee Hew, Chih Hsing Wu, Weibo Xia, Thawee Songpatanasilp, Wei Yu, Keh-Sung Tsai, Ding-Cheng Chan, Atsushi Suzuki, Ko En Huang, Kristina Åkesson, Lo-Yu Chang, Leilani B Mercado-Asis, E. Michael Lewiecki, Yoon Sok Chung, Chung-Hwan Chen, Yih Lan Gau, Jung Fu Chen, Kwang Joon Kim, Kin Bong Lee, Gau Tyan Lin, and Rong-Sen Yang
Subjects: Service (business), business.industry, Best practice, MathematicsofComputing_NUMERICALANALYSIS, Library science, Medicine, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Orthopedics and Sports Medicine, Asia pacific region, business, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), GeneralLiterature_MISCELLANEOUS
Abstract: In this article the name of the sixth author, E. Michael Lewiecki was rendered incorrectly. The publisher regrets this error and apologizes for the inconvenience caused.
Published: 2018
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37. THU0478 Before and after menopause, osteoporosis risk factors are different in women with rheumatoid arthritis

Author: Jung Fu Chen, Fu-Mei Su, Han-Ming Lai, Chung-Yuan Hsu, Wen-Chan Chiu, Tien-Tsai Cheng, Ying-Chou Chen, Shan-Fu Yu, and Ben Yu-Jih Su
Subjects: medicine.medical_specialty, business.industry, medicine.medical_treatment, Osteoporosis, Hormone replacement therapy (menopause), Odds ratio, medicine.disease, Rheumatology, Bone remodeling, Menopause, Internal medicine, Rheumatoid arthritis, medicine, Risk factor, business
Abstract: Background Rheumatoid arthritis (RA) is an autoimmune disease characterised by systemic inflammation, involving not only the juxta-articular bone erosion, but generalised bone loss[.1 Sex hormone activates RA disease activity and induced bone resorption, but hormone replacement therapy increases bone mass and density. The ambiguous role of sex hormone on bone remodelling is confusing in RA patients. Under the impact of sex hormone, risk factors for osteoporosis might be different at pre- and post-menopausal stage. Objectives To investigate the different clinical risk factors of osteoporosis in pre- and post-menopausal women with RA. Methods A cross-sectional study was performed during 2014 to 2017, enrolling female participants fulfilled 2010 RA criteria[.2 We recorded demographic data, risk factors for osteoporosis and blood test. Osteoporosis is defined if one of hip, distal forearm, and lumbar spine bone mineral density less than −2.5 by T-score for post-menopausal women, or less than −2.0 by Z-sore for pre-menopausal women. Data was analysed by Student’s t test and Chi-square test for continuous and categorical valuables, respectively. Multivariate logistic regression was applied to detect association of osteoporosis and selected variables. Results A total of 451 participants were enrolled in the study, including 89 pre- and 362 post-menopausal women. The prevalence of osteoporosis is 14.6% and 36.7% for pre- and post-menopausal women with RA, respectively. At pre-menopause, low body weight is the only significant risk factors for osteoporosis, while old age, low body height, low body weight, positive anti-cyclic citrullinated peptide antibody (anti-CCP), previous fracture history, elevated white blood cell and platelet count, and lower calcium level are potential risk factors for post-menopausal women developing osteoporosis (table 1). Multivariate stepwise logistic regression analysis (table 2) showed body weight remains the leading risk factors in pre-menopausal women (Odds ratio[OR]=0.84, 95% confidence interval [CI]=0.76~0.94, P-value=0.002), while body weight and previous fracture history are significant risk factors in post-menopausal women(body weight OR=0.91, 95% CI=0.88~0.94, P-value Conclusions Risk factors of osteoporosis are different in pre- and post-menopausal women with RA. For pre-menopausal women, Low body weight is a leading risk factor, while low body weight and previous fracture history are important for post-menopausal women. Without protection of sex hormone, there are Potential roles of anti-CCP and white blood cell participating in osteoporosis pathogenesis and need more survey for confirmation. References [1] Lems WF, Dijkmans BA: Should we look for osteoporosis in patients with rheumatoid arthritis?Ann Rheum Dis1998, 57(6):325–327. [2] Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis2010,69(9):1580–1588. Acknowledgements Special thanks to Dr. Tien-Tsai, Cheng for his effort to establish the RA-GIOP database. Disclosure of Interest None declared
Published: 2018
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38. Glycosylated hemoglobin level and number of oral antidiabetic drugs predict whether or not glycemic target is achieved in insulin-requiring type 2 diabetes

Author: Chieh-Hsiang Lu, Jung-Fu Chen, Neng-Chun Yu, Ching-Chieh Su, Chao-Hung Wang, Shih-Tzer Tsai, Shi-Dou Lin, Shih-Te Tu, Ming-Chia Hsieh, and Shang-Ren Hsu
Subjects: Blood Glucose, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Taiwan, Administration, Oral, Type 2 diabetes, Demographic data, Diabetes mellitus, Internal medicine, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Medicine, Aged, Retrospective Studies, Glycemic, Glycated Hemoglobin, Nutrition and Dietetics, business.industry, Basal insulin, Middle Aged, medicine.disease, Surgery, Treatment Outcome, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Observational study, Hemoglobin, Family Practice, business, Biomarkers
Abstract: Factors predicting success (glycosylated hemoglobin (A1C)7%) with insulin therapy in patients with insulin-requiring type 2 diabetes need to be identified.A retrospective, multi-center, observational study was conducted for outpatients with oral antidiabetic drug (OAD)-treated type 2 diabetes whose A1C levels remained above 7%. Patients were begun on basal insulin between January 2005 and December 2006. Biochemical variables and demographic data were collected before and after 52 weeks of insulin therapy.A total of 565 patients (age, 60.4±11.9 years; A1C levels, 10.11 ±1.81%; duration of diabetes, 11.5±6.8 years) were studied. By study end, 63 patients (11.2%) had achieved the glycemic goal (A1C7%). The glycemic goal attainment rate was only 9.1% in patients with A1C8.8% and who were taking2 OADs at baseline. The highest rate (32.7%) of successful glycemic control was observed in the group of patients with A1C ≤ 8.8% and who used ≤ 2 OADs at baseline.Insulin-naïve diabetic patients with A1C8.8%, especially those who are taking2 OADs, have small chance to achieve good glycemic control with adding only basal insulin therapy.
Published: 2015
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39. 2018 consensus of the Taiwan Society of Cardiology and the Diabetes Association of Republic of China (Taiwan) on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases

Author: Chien-Ning Huang, Tsung-Hsien Lin, Yen-Wen Wu, Shih-Yi Lin, Lee-Ming Chuang, Ping Yen Liu, Chia Ti Tsai, Yi-Heng Li, San Jou Yeh, Shing Jong Lin, Kou Gi Shyu, Jung Fu Chen, Hung I. Yeh, Shyi Jang Shin, Wei Hsian Yin, Chern En Chiang, Tzung-Dau Wang, Kwo Chang Ueng, Jiunn Lee Lin, Wayne Huey-Herng Sheu, Hao Min Cheng, Wei-Shiung Yang, Pao-Hsien Chu, Yi Jen Hung, Ting-Hsing Chao, Kuan-Cheng Chang, and Kang Ling Wang
Subjects: medicine.medical_specialty, Consensus, Cardiology, Taiwan, Heart failure, Type 2 diabetes, 030204 cardiovascular system & hematology, Hypoglycemia, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Chronic kidney disease, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Stroke, Societies, Medical, Glycated Hemoglobin, lcsh:R5-920, business.industry, Anti-diabetic agents, General Medicine, medicine.disease, Clinical trial, Coronary heart disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Hypertension, business, lcsh:Medicine (General), Kidney disease, Cohort study, Glomerular Filtration Rate
Abstract: The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type 2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15% from heart failure (HF), and 10% from stroke. The association between hyperglycemia and elevated CV risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction did not significantly reduce macrovascular outcomes. It remains unclear whether the absence of demonstrable benefits is attributed to the inclusion of patients with far advanced ASCVD in whom a short treatment period is barely enough for CV protective effects to be shown, or complications associated with the treatment such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose-lowering per se is ineffective. Since the US FDA issued a mandate in December 2008 that every new anti-diabetic agent requires rigorous assessments of its CV safety, there have been more than 200,000 patients enrolled in a number of randomized controlled trials (RCTs), and around half of them have been completed and published. The results of these CV outcome trials are important for clinicians in their clinical practice, and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases. The Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients with CVD, have appointed a jointed consensus group for the 2018 Consensus of TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2 Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1) Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic kidney disease, 4) Treatment of diabetes in patients with a history of stroke, and 5) Treatment of diabetes in patients with HF. The members of the consensus group comprehensively reviewed all the evidence, mainly RCTs, and also included meta-analyses, cohort studies, and studies using claim data. The treatment targets of HbA1c were provided. The anti-diabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.
Published: 2018

40. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author: Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John 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Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. 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Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, 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Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González Juanatey, José Ramón, Hernandez Mijares, Antonio, Jiménez Díaz, Víctor Alfonso, Jodar Gimeno, Esteban, Lucas Morante, Tomá, Marazuela, Monica, Martell Claros, Nieve, Mauricio Puente, Didac, Mena Ribas, Elena, Merino Torres, Juan Francisco, Mezquita Raya, Pedro, Nubiola Calonge, Andreu, Ordoñez Sánchez, Xavier, Pascual Izuel, Jose Maria, Perea Castilla, Verónica, Pérez Pérez, Antonio, Perez Soto, Isabel, Quesada Charneco, Miguel, Quesada Simón, Angustia, Redón Mas, Josep, Rego Iraeta, Antonia, Rodriguez Alvarez, Maria, Rodríguez Rodríguez, Irene, Sabán Ruiz, José, Soto González, Alfonso, Tinahones Madueno, Francisco, Trescoli Serrano, Carlo, Ulied Armiñana, Angel, Bachus, Erasmu, Berndtsson Blom, Katarina, Eliasson, Ken, Koskinen, Pekka, Larnefeldt, Han, Lif-Tiberg, Cornelia, Linderfalk, Carina, Lund, Gustav, Lundman, Pia, Moris, Linda, Olsson, Åke, Salmonsson, Staffan, Sanmartin Berglund, Johan, Sjöberg, Folke, Söderberg, Stefan, Torstensson, Ingemar, Chen, Jung-Fu, Tien, Kai Jen, Tseng, Shih-Ting, Tu, Shih-Te, Wang, Chih-Yuan, Wang, Ji-Hung, Phrommintikul, Arintaya, Yamwong, Sukit, Jintapakorn, Woravut, Hutayanon, Pisit, Sansanayudh, Nakarin, Bazhan, Larysa, Fushtey, Ivan, Grachova, Mariya, Katerenchuk, Vitaliy, Korpachev, Vadym, Kravchun, Nonna, Larin, Oleksandr, Mykhalchyshyn, Galyna, Myshanych, Halyna, Oleksyk, Olga, Orlenko, Valeriia, Pashkovska, Nataliia, Pertseva, Nataliia, Petrosyan, Olena, Smirnov, Ivan, Vlasenko, Maryna, Zlova, Tetiana, Aye, Myint, Baksi, Arun, Balasubramani, Mathangi, Beboso, Ronnie, Blagden, Mark, Bundy, Charle, Cookson, Tobia, Copland, Allan, Emslie-Smith, Alistair, Green, Fiona, Gunstone, Anthony, Issa, Basil, Jackson-Voyzey, Ewart, Johnson, Andrew, Maclean, Malcolm, Mcknight, John, Muzulu, Solomon, O'Connell, Ian, Oyesile, Babatunde, Patterson, Catherine, Pearson, Ewan, Philip, Sam, Smith, Paul, Sukumaran, Usha, Abbas, Jalal, Aggarwala, Gaurav, Akhter, Faiq, Andersen, Jame, Anglade, Moise, Argoud, George, Ariani, Mehrdad, Ashdji, Reswan, Bakhtari, Ladan, Banerjee, Subhash, Bartlett, Andrew, Baum, Howard, Bays, Harold, Beasley, Richard, Belfort de Aguiar, Renata, Benjamin, Sabrina, Bhagwat, Ravi, Bhargava, Anuj, Bode, Bruce, Bratcher, Christina, Briskin, Toby, Brockmyre, Andrew, Broughton, Raymond, Brown, Judith, Budhraja, Madhusudan, Cannon, Kevin, Carr, Jewell, Cathcart, Harold, Cavale, Arvind, Chaykin, Loui, Cheung, Deanna, Childress, Richard, Cohen, Allan, Condit, Jonathan, Cooksey, Erin, Cornett, George Mitchell, Dauber, Ira, Davila, William, De Armas, Lui, Dean, Juliu, Detweiler, Robert, Diaz, Ernesto, Di Giovanna, Michael, Dor, Isaac, Drummond, Waymon, Eagerton, Donald, Earl, John, Eaton, Charle, Ellison, Howard, Farris, Neil, Fiel, Thoma, Firek, Anthony, First, Brian, Forgosh, Le, French, William, Gandy, Winston, Garcia, Ronald, Gill, Santosh, Gordon, Murray, Guice, Michael, Gummadi, Siva, Hackenyos, Jonathan, Hairston, Kristen, Hanson, Lenita, Harrison, Lindsay, Hartman, Israel, Heitner, John, Hejeebu, Srini, Hermany, Paul, Hernandez-Cassis, Carlo, Hidalgo, Horacio, Higgins, Alexander, Ibrahim, Hassan, Jacobs, Shahram, Johnson, David, Joshi, Parag, Kaster, Steven, Kellum, Daniel, Kim, Christopher, Kim, Ellen, Kirby, William, Knouse, Albert, Kulback, Steven, Kumar, Mariananda, Kuruvanka, Tulsida, Labroo, Ajay, Lasswell, William, Lentz, John, Lenzmeier, Thoma, Lewis, David, Li, Zhaoping, Lillestol, Michael, Little, Raymond, Lorraine, Richard, McKeown-Biagas, Cecilia, Mcneill, Robert, Mehta, Anand, Miller, Alan, Moran, Joseph, Morawski, Emily, Nadar, Venkatesh, O'Connor, Thoma, Odio, Alberto, Parker, Reginald, Patel, Rajesh, Phillips, Lawrence, Raad, George, Rahman, Aref, Raikhel, Marina, Raisinghani, Ajit, Rajan, Raj, Rasouli, Neda, Rauzi, Frank, Rohr, Kathryn, Roseman, Hal, Rovner, Sergio, Saba, Fadi, Sachson, Richard, Schabauer, Alex, Schneider, Ricky, Schuchard, Timothy, Sensenbrenner, John, Shlesinger, Yshay, Singh, Narendra, Sivalingam, Kanagaratnam, Stonesifer, Larry, Storey, Daniel, Suh, David, Tahir, Mohammed, Tan, Anjanette, Tan, Marilyn, Taylon, Alain, Thakkar, Maitreya, Tripathy, Devjit, Uwaifo, Gabriel, Vedere, Amarnath, Venugopal, Chandra, Vo, Anthony, Welch, Michelle, Welker, Jame, White, Alexander, Willis, John, Wynne, Alan, Yazdani, Shahram, Rosenberg, Anne, Price, Lauren, Sigmon, Kristina, Lokhngina, Yuliya, Xing, Weibing, Overton, Robert, Stewart, Murray, Stead, Janet, Lindsay, Alistair, Patel, Vicka, Ross, Jorge, Soffer, Joseph, Daga, Shruti, Sowell, Margaret, Patel, Prashant, Garvey, Louisa, Ackert, Jessica, Abraham, Sybil, Sabol, Mary Beth, Altobelli, Desma, Ha, Juyoung, Kulkarni, Mangesh, Somerville, Matthew, Noronha, Drusilla, Casson, Ed, Zang, Eddie, Sandhu, Chamandeep, Kumar, Rakesh, Chen, David, Taft, Lin, Patel, Rajivkumar, Ye, June, Shannon, Jennifer, Wilson, Tim, Babi, Charleen, Miller, Diane, Thorpe, Karl, Russell, Rachael, Bull, Georgina, Hereghty, Belinda, Fernandez-Salazar, Eva, Longley, Troy, Donaldson, Jill, Jarosz, Marie, Murphy, Karen, Adams, Patricia, Smith, Peter, James, Rachel, Richards, Jackie, Sedani, Sangeeta, Althouse, Denise, Watson, David, Lorimer, Jamie, Lauder, Steven, Schultheis, Ron, Womer, Terese, Wraight, Ella, Li, Wenyan, Price-Olsen, Emma, Watson, Anthony, Kelly, Aoife, Mclaughlin, Patricia, Fleming, John, Schubert, Jessica, Schleiden, Debra, Harris, Tara, Prakash, Rahul, Breneman, Jody, Deshpande, Sameer, Saswadkar, Aarti, Kumari, Aditi, Shitut, Aditi, Raorane, Amruta, Karmalkar, Anisha, Mhambrey, Ankita, Bhosale, Archana, Vaphare, Ashok, Patil, Ashwini P, Khandelwal, Chaitali, Shaik, Fayaz, Nadar, Madhumitha, Karka, Mounika, Kadgaonkar, Neha, Gupta, Nikita, Aher, Nutan, Potnis, Omkar, Naicker, Pallavi, Shinde, Rakesh, Sharma, Richa, Godse, Rupali, Solanki, Sheetal, Sahu, Shruti, Dumbre, Snehal, Kumar, Somesh, Patil, Suradnya, Mandal, Trisha, McMurray, John J V, McMurray, John J.V., DeMets, David, McGuire, Darren, Groutars, Reginald G.E.J., Hoogslag, Pieter A.M., McKnight, John, McNeill, Robert, Ha, JuYoung, McLaughlin, Patricia, Hernandez, A. 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M., Dauber, I., Davila, W., De Armas, L., Dean, J., Detweiler, R., Diaz, E., Di Giovanna, M., Dor, I., Drummond, W., Eagerton, D., Earl, J., Eaton, C., Ellison, H., Farris, N., Fiel, T., Firek, A., First, B., Forgosh, L., French, W., Gandy, W., Garcia, R., Gill, S., Gordon, M., Guice, M., Gummadi, S., Hackenyos, J., Hairston, K., Hanson, L., Harrison, L., Hartman, I., Heitner, J., Hejeebu, S., Hermany, P., Hernandez-Cassis, C., Hidalgo, H., Higgins, A., Ibrahim, H., Jacobs, S., Johnson, D., Joshi, P., Kaster, S., Kellum, D., Kim, C., Kim, E., Kirby, W., Knouse, A., Kulback, S., Kumar, M., Kuruvanka, T., Labroo, A., Lasswell, W., Lentz, J., Lenzmeier, T., Lewis, D., Li, Z., Lillestol, M., Little, R., Lorraine, R., McKeown-Biagas, C., Mcneill, R., Mehta, A., Miller, A., Moran, J., Morawski, E., Nadar, V., O'Connor, T., Odio, A., Parker, R., Patel, R., Phillips, L., Raad, G., Rahman, A., Raikhel, M., Raisinghani, A., Rajan, R., Rasouli, N., Rauzi, F., Rohr, K., Roseman, H., Rovner, S., Saba, F., Sachson, R., Schabauer, A., Schneider, R., Schuchard, T., Sensenbrenner, J., Shlesinger, Y., Singh, N., Sivalingam, K., Stonesifer, L., Storey, D., Suh, D., Tahir, M., Tan, A., Tan, M., Taylon, A., Thakkar, M., Tripathy, D., Uwaifo, G., Vedere, A., Venugopal, C., Vo, A., Welch, M., Welker, J., White, A., Willis, J., Wynne, A., Yazdani, S., Price, L., Lokhngina, Y., Xing, W., Overton, R., Stewart, M., Stead, J., Lindsay, A., Patel, V., Ross, J., Soffer, J., Daga, S., Sowell, M., Patel, P., Garvey, L., Ackert, J., Abraham, S., Sabol, M. B., Altobelli, D., Ha, J., Kulkarni, M., Noronha, D., Casson, E., Zang, E., Sandhu, C., Kumar, R., Chen, D., Taft, L., Ye, J., Shannon, J., Wilson, T., Babi, C., Miller, D., Russell, R., Bull, G., Hereghty, B., Fernandez-Salazar, E., Longley, T., Donaldson, J., Jarosz, M., Murphy, K., Adams, P., James, R., Richards, J., Sedani, S., Althouse, D., Watson, D., Lorimer, J., Lauder, S., Schultheis, R., Womer, T., Wraight, E., Li, W., Price-Olsen, E., Watson, A., Kelly, A., Mclaughlin, P., Fleming, J., Schubert, J., Schleiden, D., Harris, T., Prakash, R., Breneman, J., Deshpande, S., Saswadkar, A., Kumari, A., Shitut, A., Raorane, A., Karmalkar, A., Mhambrey, A., Bhosale, A., Vaphare, A., Patil, A. P., Khandelwal, C., Shaik, F., Nadar, M., Karka, M., Kadgaonkar, N., Gupta, N., Aher, N., Potnis, O., Naicker, P., Shinde, R., Sharma, R., Godse, R., Solanki, S., Sahu, S., Dumbre, S., Kumar, S., Patil, S., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, C, Kocsis, G, Giaccari, A, Lee, M, Munoz, E, Cornel, J, Birkeland, K, Pinto, M, Tirador, L, Olesinska-Mader, M, Shestakova, M, Distiller, L, Lopez-Sendon, J, Eliasson, B, Chiang, C, Srimahachota, S, Mankovsky, B, Bethel, M, Dungan, K, Kosiborod, M, Alvarisqueta, A, Baldovino, J, Besada, D, Calella, P, Cantero, M, Castano, P, Chertkoff, A, Cuadrado, J, De Loredo, L, Dominguez, A, Espanol, M, Finkelstein, H, Frechtel, G, Fretes, J, Garrido Santos, N, Gonzalez, J, Litvak, M, Loureyro, J, Maffei, L, Maldonado, N, Mohr Gasparini, D, Orio, S, Perez Manghi, F, Rodriguez Papini, N, Sala, J, Schygiel, P, Sposetti, G, Ulla, M, Verra, F, Zabalua, S, Zaidman, C, Crenier, L, Debroye, C, Duyck, F, Scheen, A, Van Gaal, L, Vercammen, C, Damyanova, V, Dimitrov, S, Kovacheva, S, Lozanov, L, Margaritov, V, Mihaylova-Shumkova, R, Nikolaeva, A, Stoyanova, Z, Akhras, R, Beaudry, Y, Bedard, J, Berlingieri, J, Chehayeb, R, Cheung, S, Conway, J, Cusson, J, Della Siega, A, Dumas, R, Dzongowski, P, Ferguson, M, Gaudet, D, Grondin, F, Gupta, A, Gupta, M, Halperin, F, Houle, P, Jones, M, Kouz, S, Kovacs, C, Landry, D, Lonn, E, O'Mahony, W, Peterson, S, Reich, D, Rosenbloom, A, St-Maurice, F, Tugwell, B, Vizel, S, Woo, V, Brychta, T, Cech, V, Dvorakova, E, Edelsberger, T, Halciakova, K, Krizova, J, Lastuvka, J, Piperek, M, Prymkova, V, Raclavska, L, Silhova, E, Urbanek, R, Vrkoc, J, Andersen, U, Bronnum-Schou, J, Hove, J, Jensen, J, Kober, L, Kristiansen, O, Lund, P, Melchior, T, Nyvad, O, Schou, M, Boye, A, Cadinot, D, Gouet, D, Henry, P, Kessler, L, Lalau, J, Petit, C, Thuan, J, Voinot, C, Vouillarmet, J, Axthelm, C, Berger, D, Bieler, T, Birkenfeld, A, Bott, J, Busch, K, Caca, K, Chevts, J, Donaubauer, T, Erlinger, R, Funke, K, Grosskopf, J, Hagenow, A, Hamann, M, Hartard, M, Heymer, P, Huppertz, W, Illies, G, Jacob, S, Jung, T, Kahrmann, G, Kast, P, Kellerer, M, Kempe, H, Khariouzov, A, Klausmann, G, Klein, C, Kleinecke-Pohl, U, Kleinertz, K, Koch, T, Kosch, C, Lorra, B, Luedemann, J, Luttermann, M, Maxeiner, S, Milek, K, Moelle, A, Neumann, G, Nischik, R, Oehrig-Pohl, E, Plassmann, G, Pohlmeier, L, Proepper, F, Regner, S, Rieker, W, Rose, L, Samer, H, Sauter, J, Schaper, F, Schiffer, C, Schmidt, J, Scholz, B, Schulze, J, Segner, A, Seufert, J, Sigal, H, Steindorf, J, Stockhausen, J, Stuebler, P, Taeschner, H, Tews, D, Tschoepe, D, Wilhelm, K, Zeller-Stefan, H, Avramidis, I, Bousboulas, S, Bristianou, M, Dimitriadis, G, Elisaf, M, Kotsa, K, Melidonis, A, Mitrakou, A, Pagkalos, E, Papanas, N, Pappas, A, Sampanis, C, Tentolouris, N, Tsapas, A, Tzatzagou, G, Ozaki, R, Hajdu, C, Harcsa, E, Konyves, L, Mucsi, J, Pauker, Z, Petro, G, Ples, Z, Revesz, K, Sandor, V, Vass, V, Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
Subjects: Male, Placebo-controlled study, Myocardial Infarction, alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Glucagon-Like Peptide 1, Cardiovascular Disease, Medicine(all), education.field_of_study, Subcutaneous, Medicine (all), albigutide, Hazard ratio, General Medicine, Middle Aged, Albiglutide, Stroke, Treatment Outcome, Tolerability, Cardiovascular Diseases, Female, type 2 diabetes, Type 2, Human, Adult, medicine.medical_specialty, Injections, Subcutaneous, Population, 030209 endocrinology & metabolism, Placebo, Injections, Subcutaneou, Drug Administration Schedule, Injections, 03 medical and health sciences, Double-Blind Method, Internal medicine, Diabetes Mellitus, medicine, Humans, Hypoglycemic Agents, education, Aged, Diabetes Mellitus, Type 2, Hypoglycemic Agent, business.industry, Semaglutide, Settore MED/13 - ENDOCRINOLOGIA, Harmony, business
Abstract: Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
Published: 2018

41. Consensus on best practice standards for Fracture Liaison Service in the Asia-Pacific region

Author: Lo-Yu Chang, Ding Cheng Derrick Chan, Thawee Songpatanasilp, Kwang Joon Kim, Yin Fan Chang, Weibo Xia, Joon Kiong Lee, Keh-Sung Tsai, Kristina Åkesson, Wei Yu, Yih Lan Gau, Atsushi Suzuki, Gau Tyan Lin, Kin Bong Lee, Leilani B Mercado-Asis, Ko En Huang, Chung-Hwan Chen, Rong-Sen Yang, E. Michael Lewiecki, Yoon Sok Chung, Jung Fu Chen, Fen Lee Hew, Tang Ching Lau, Chih Hsing Wu, Peter R. Ebeling, and Paul Mitchell
Subjects: 0301 basic medicine, Asia, Consensus, Family education, Steering committee, Best practice, media_common.quotation_subject, 030209 endocrinology & metabolism, Asia pacific region, 03 medical and health sciences, 0302 clinical medicine, Asia pacific, Secondary Prevention, Medicine, Humans, Orthopedics and Sports Medicine, Societies, Medical, media_common, Final version, Medical education, Australasia, business.industry, Congresses as Topic, Service (economics), Healthcare settings, 030101 anatomy & morphology, business, Delivery of Health Care, Osteoporotic Fractures
Abstract: The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.
Published: 2017

42. Fracture liaison services improve outcomes of patients with osteoporosis-related fractures: A systematic literature review and meta-analysis

Author: Manikanta Dasari, Ding-Cheng Chan, Shih Te Tu, Keh-Sung Tsai, Sonal Singh, Jui Teng Chien, Chih Hsueh Lin, Yin Fan Chang, Jung Fu Chen, and Chih Hsing Wu
Subjects: 0301 basic medicine, medicine.medical_specialty, Histology, lcsh:Diseases of the musculoskeletal system, Physiology, Endocrinology, Diabetes and Metabolism, Osteoporosis, 030209 endocrinology & metabolism, Cochrane Library, 03 medical and health sciences, 0302 clinical medicine, Bone Density, Internal medicine, Secondary Prevention, Humans, Medicine, 030212 general & internal medicine, Aged, Randomized Controlled Trials as Topic, Aged, 80 and over, business.industry, Incidence (epidemiology), Absolute risk reduction, Middle Aged, medicine.disease, Confidence interval, Observational Studies as Topic, Treatment Outcome, Systematic review, Meta-analysis, Physical therapy, Observational study, 030101 anatomy & morphology, lcsh:RC925-935, business, Osteoporotic Fractures
Abstract: Objectives This systematic review and meta-analysis evaluated the outcomes of patients with osteoporosis-related fractures managed through fracture liaison services (FLS) programs. Methods Medline, PubMed, EMBASE, and the Cochrane Library were searched (January 2000–February 2017 inclusive) using the keywords ‘osteoporosis’, ‘fractures’, ‘liaison’, and ‘service’ to identify randomised controlled trials and observational studies of patients aged ≥50 years with osteoporosis-related fractures in hospital, clinic, community, or home-based settings who were managed using FLS. Risk of bias was assessed at outcome level. Meta-analysis followed a random-effects and fixed-effects model. Outcomes of interest were incidence of bone mineral density (BMD) testing, treatment initiation, adherence, re-fractures, and mortality due to osteoporosis treatment. Results A total of 159 publications were identified for the systematic literature review; 74 controlled studies (16 RCTs; 58 observational studies) were included in the meta-analysis. Overall, 41 of 58 observational studies and 12 of 16 RCTs were considered of high quality. Compared with patients receiving usual care (or those in the control arm), patients receiving care from an FLS program had higher rates of BMD testing (48.0% vs 23.5%) and treatment initiation (38.0% vs 17.2%) and greater adherence (57.0% vs 34.1%). Unweighted average rates of re-fracture were 13.4% among patients in the control arm and 6.4% in the FLS arm. Unweighted average rates of mortality were 15.8% in the control arm and 10.4% in the FLS arm. Meta-analysis revealed significant FLS-associated improvements in all outcomes versus non-FLS controls, with BMD testing increased by 24 percentage points (95% confidence interval [CI] 0.18–0.29), 20 percentage points for treatment rates (95% CI 0.16–0.25), and 22 percentage points for adherence (95% CI 0.13–0.31) and absolute risk of re-fracture reduced by five percentage points (95% CI –0.08 to −0.03) and mortality reduced by three percentage points (95% CI –0.05 to −0.01). Conclusion FLS programs improved outcomes of osteoporosis-related fractures, with significant increases in BMD testing, treatment initiation, and adherence to treatment and reductions in re-fracture incidence and mortality.
Published: 2017

43. Transient elastography as a screening tool for liver fibrosis in a large hemodialysis population

Author: Kuo-Chin Chang, Jin-Bor Chen, Jung-Ting Lin, Jung-Fu Chen, Ben-Chung Cheng, Tsung-Hui Hu, Ming-Chao Tsai, Yi-Hao Yen, Cheng-Kun Wu, Po-Lin Tseng, and Ming-Tsung Lin
Subjects: 0301 basic medicine, Liver Cirrhosis, Male, medicine.medical_specialty, medicine.medical_treatment, Population, Taiwan, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Non-alcoholic Fatty Liver Disease, Renal Dialysis, Risk Factors, Internal medicine, Prevalence, Medicine, Humans, Mass Screening, education, Aged, Metabolic Syndrome, education.field_of_study, Multidisciplinary, business.industry, Fatty liver, Hepatitis B, Middle Aged, medicine.disease, 030104 developmental biology, Liver, Elasticity Imaging Techniques, Kidney Failure, Chronic, 030211 gastroenterology & hepatology, Female, Hemodialysis, Steatosis, Metabolic syndrome, business, Transient elastography
Abstract: Metabolic syndrome, an etiological factor in non-alcoholic fatty liver disease (NAFLD), is often present in hemodialysis patients. Little is known about the prevalence of, and factors associated with, liver fibrosis in hemodialysis populations. We used transient elastography (TE) to investigate these phenomena. 659 patients treated with chronic hemodialysis were enrolled. We excluded those with excess alcohol intake, liver stiffness measurement (LSM) failure, or unreliable LSM values. LSM ≥8.0 kPa was used as a cutoff suggesting clinically relevant fibrosis. Controlled attenuation parameter (CAP) ≥ 232.5 dB/m was used as a cutoff suggesting steatosis. 333 patients (50.5%) had steatosis, 159 (24.1%) had hepatitis B or C, and 149 (22.6%) had LSM ≥8.0 kPa. In multivariable analyses, male gender (OR: 2.16; 95% CI: 1.29–3.63; P = 0.004), overweight body habitus (OR:2.31; 95% CI: 1.35–3.94; P = 0.002), high AST level (OR:1.08; 95% CI: 1.04–1.12; P
Published: 2017
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44. The correlation of controlled attenuation parameter results with ultrasound-identified steatosis in real-world clinical practice

Author: Cheng-Kun Wu, Kuo-Chin Chang, Ming-Chao Tsai, Jung-Fu Chen, Yi-Hao Yen, Po-Lin Tseng, Ming-Tsung Lin, Tsung-Hui Hu, and Jung-Ting Lin
Subjects: Adult, Male, medicine.medical_specialty, Steatosis, Hepatitis C virus, Taiwan, Chronic liver disease, medicine.disease_cause, Gastroenterology, Severity of Illness Index, Correlation, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Internal medicine, Ultrasound, medicine, Chronic viral hepatitis, Humans, Aged, Ultrasonography, Hepatitis B virus, lcsh:R5-920, Receiver operating characteristic, business.industry, General Medicine, Middle Aged, medicine.disease, Hepatitis B, Hepatitis C, Clinical Practice, Fatty Liver, Liver, ROC Curve, 030220 oncology & carcinogenesis, Area Under Curve, Controlled attenuation parameter, Multivariate Analysis, Linear Models, 030211 gastroenterology & hepatology, Female, lcsh:Medicine (General), business
Abstract: Controlled attenuation parameter (CAP) is a method for measuring steatosis based on FibroScan. Despite observer dependency, ultrasound (US) robustly diagnoses moderate and severe steatosis. Here, we aimed to evaluate the correlation of CAP with US-identified steatosis in real-world clinical practice. Methods: CAP and US were performed for 1554 chronic liver disease (CLD) patients. CAP was performed by two technicians, and US was performed by 30 hepatologists. The performance of the CAP as compared with the US results was assessed using the area under the receiver operating characteristic curve (AUROC). Results: 532 (34.2%) of the patients had hepatitis C virus (HCV) infection, 723 (46.5%) of the patients had hepatitis B virus (HBV) infection, and the rest were patients with metabolic risk factors. CAP values were significantly correlated with the steatosis grades identified by US for all the patients (ρ = 0.497, P
Published: 2017

45. A systematic review on the use of daily subcutaneous administration of teriparatide for treatment of patients with osteoporosis at high risk for fracture in Asia

Author: H. Sowa, Y. Chen, H.C. Chang, Sirel Gurbuz, Jung-Fu Chen, K. H. Yang, and Zhijian Zhang
Subjects: Male, medicine.medical_specialty, Asia, Bone density, Injections, Subcutaneous, Endocrinology, Diabetes and Metabolism, Osteoporosis, Placebo, Drug Administration Schedule, law.invention, Asian People, Randomized controlled trial, Bone Density, law, Teriparatide, Elcatonin, Internal medicine, Humans, Medicine, Osteoporosis, Postmenopausal, Bone Density Conservation Agents, business.industry, medicine.disease, Tolerability, Physical therapy, Female, business, Osteonecrosis of the jaw, Osteoporotic Fractures, medicine.drug
Abstract: This systematic review aimed to examine the evidence for teriparatide in Asia for osteoporosis with a high fracture risk and for exploratory (unapproved) bone-related indications. MEDLINE (1946+), EMBASE (1966+), and ClinicalTrials.gov (2008+) were searched (16 August 2013); all studies of daily subcutaneous teriparatide 20 μg for bone-related conditions from China, Hong Kong, Japan, Republic of Korea, Philippines, Singapore, and Taiwan were included. Evidence on efficacy/safety was retrieved primarily from randomized controlled trials (10 publications) of postmenopausal women from Japan and China. In these studies, teriparatide was well tolerated; subjects had significantly greater increases in lumbar spine bone mineral density (BMD) from baseline compared with placebo, antiresorptive agents, or elcatonin/calcitonin; bone turnover markers increased from baseline and were sustained at elevated levels during teriparatide treatment. Few studies reported fracture risk, pain, or quality of life; one study showed a lower incidence of new-onset vertebral fracture with teriparatide versus antiresorptive agents. Nonrandomized studies (nine publications, one unpublished trial) conducted mainly in Taiwan, Japan, and the Republic of Korea provided supporting data for efficacy. The exploratory (unapproved) use of teriparatide (17 publications) for fracture healing and osteonecrosis of the jaw was described primarily in case reports. The clinical effectiveness of teriparatide for treatment of postmenopausal women with osteoporosis who are at high risk of fracture in Asia is focused primarily on improvements in BMD and tolerability. Recommended additional studies may include assessment of fracture risk and the effect of teriparatide on pain, quality of life, and mortality in Asia.
Published: 2014
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46. Clinical practice guidelines for the prevention and treatment of osteoporosis in Taiwan: summary

Author: Ding-Cheng Chan, Jawl Shan Hwang, Chih Hsing Wu, Yung Kuei Soong, Tien Tsai Cheng, Keh-Sung Tsai, Rong-Sen Yang, and Jung Fu Chen
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Osteoporosis, Taiwan, MEDLINE, Alternative medicine, Endocrinology, Bone Density, Epidemiology, medicine, Humans, Orthopedics and Sports Medicine, Reimbursement, Bone Density Conservation Agents, business.industry, Public health, General Medicine, Guideline, medicine.disease, Radiography, Clinical Practice, Family medicine, Practice Guidelines as Topic, Physical therapy, Bone Remodeling, Public Health, business
Abstract: Osteoporosis is recognized as a major public health problem worldwide and in Taiwan. However, many patients with osteoporotic fractures do not receive appropriate assessments or treatments. This guideline, proposed by the Taiwanese Osteoporosis Association, is to serve as a quick reference for healthcare providers to improve the assessment of osteoporosis and development of optimal strategies for osteoporotic management in Taiwan. To review and update osteoporosis management, the guideline is constituted with Taiwan-specific osteoporosis epidemiological data, medication protocols, and the 10-year FRAX(®). The guideline is based on evidence-based medicine and public health considerations. Recommendations are not limited to the reimbursement regulations permitted by the National Health Insurance of Taiwan.
Published: 2013
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47. Using controlled attenuation parameter combined with ultrasound to survey non-alcoholic fatty liver disease in hemodialysis patients: A prospective cohort study

Author: Yi-Hao Yen, Kuo-Chin Chang, Ming-Chao Tsai, Po-Lin Tseng, Tsung-Hui Hu, Ming-Tsung Lin, Cheng-Kun Wu, Jin-Bor Chen, Ben-Chung Cheng, and Jung-Fu Chen
Subjects: Male, Steatosis, Physiology, medicine.medical_treatment, Biopsy, lcsh:Medicine, Aminotransferases, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Gastroenterology, Biochemistry, Body Mass Index, Cytopathology, 0302 clinical medicine, Endocrinology, Non-alcoholic Fatty Liver Disease, Medicine and Health Sciences, Prospective Studies, Prospective cohort study, lcsh:Science, Ultrasonography, Multidisciplinary, medicine.diagnostic_test, Liver Diseases, Fatty liver, Middle Aged, Enzymes, Physiological Parameters, Nephrology, 030211 gastroenterology & hepatology, Female, Hemodialysis, Research Article, medicine.medical_specialty, Endocrine Disorders, Lipoproteins, Surgical and Invasive Medical Procedures, Gastroenterology and Hepatology, 03 medical and health sciences, Renal Dialysis, Transferases, Internal medicine, Diabetes mellitus, Medical Dialysis, medicine, Diabetes Mellitus, Humans, Aged, business.industry, lcsh:R, Body Weight, Biology and Life Sciences, Proteins, medicine.disease, Surgery, Fatty Liver, Anatomical Pathology, Metabolic Disorders, Enzymology, lcsh:Q, business, Body mass index, Dyslipidemia
Abstract: Background and aims Controlled attenuation parameter (CAP) is a non-invasive method for measuring hepatic steatosis (HS). Non-alcoholic fatty liver disease (NAFLD) is closely related to cardiovascular diseases (CVDs). CVDs are the leading cause of morbidity and mortality in hemodialysis patients. The aim of this study was to investigate the prevalence of NAFLD in hemodialysis patients. Method We prospectively enrolled patients undergoing chronic hemodialysis, as well as patients with normal renal function who served as controls. The control group patients were referred by an endocrinologist to be tested for NAFLD; most of these patients had diabetes, hypertension, or dyslipidemia. We excluded those with excess alcohol intake, use of drugs known to induce HS, chronic viral hepatitis, or CAP failure. CAP ≥ 238 dB/m was used as a cutoff suggesting HS. An increased liver kidney contrast, as defined by ultrasound, was used to make the diagnosis of HS. Results Three hundred and forty-three hemodialysis patients and 252 control group patients were enrolled. Among the hemodialysis patients, 192 (56.0%) had CAP- or ultrasound-identified HS compared with 91 (26.5%) who only had ultrasound-identified HS (P
Published: 2017

48. Clinical Characteristics of Endogenous Cushing’s Syndrome at a Medical Center in Southern Taiwan

Author: Joseph W. Yang, Wei-Ching Lee, Tao-Chen Lee, Shih-Chen Tung, Ming-Chun Kuo, Min-Hsiung Cheng, Jung-Fu Chen, Ching-Jung Hsieh, Pei-Wen Wang, and Rue-Tsuan Liu
Subjects: medicine.medical_specialty, lcsh:RC648-665, Article Subject, Endocrine and Autonomic Systems, business.industry, Endocrinology, Diabetes and Metabolism, Incidence (epidemiology), Adrenalectomy, medicine.medical_treatment, Endogeny, medicine.disease, lcsh:Diseases of the endocrine glands. Clinical endocrinology, Gastroenterology, Adrenocortical adenoma, Endocrinology, Dexamethasone suppression test, Internal medicine, Clinical Study, medicine, Adrenocortical carcinoma, Circadian rhythm, Differential diagnosis, business
Abstract: From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing’s syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing’s disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days,P<0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.
Published: 2013
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49. Long-term use of acarbose and CV Event: confusing finding from mega data bank

Author: Kun‐Ling Wu, Zih Jie Sun, Chen‐Jung Shen, Shih‐Te Tu, Jung‐Fu Chen, Ming‐Fong Chang, and Chih Hsing Wu
Subjects: Blood Glucose, business.industry, Endocrinology, Diabetes and Metabolism, Event (relativity), 030209 endocrinology & metabolism, Mega, Data science, Term (time), 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes Mellitus, Type 2, Internal Medicine, Data bank, Medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Acarbose, business, medicine.drug
Published: 2016

50. Incidence and prevalence rates of diabetes mellitus in Taiwan: Analysis of the 2000–2009 Nationwide Health Insurance database

Author: Lee-Ming Chuang, Yi-Der Jiang, Jung-Fu Chen, Tong-Yuan Tai, and Chia-Hsuin Chang
Subjects: Gerontology, Adult, Male, Catastrophic illness, medicine.medical_specialty, Adolescent, Databases, Factual, National Health Programs, Population, prevalence, Prevalence, Taiwan, Young Adult, Diabetes mellitus, Epidemiology, medicine, Humans, education, Child, Aged, Retrospective Studies, Medicine(all), Aged, 80 and over, Type 1 diabetes, education.field_of_study, lcsh:R5-920, business.industry, Incidence (epidemiology), Infant, Newborn, Infant, General Medicine, Middle Aged, medicine.disease, Survival Rate, Child, Preschool, diabetes mellitus, incidence, Female, Diagnosis code, business, lcsh:Medicine (General), Taiwan National Health Insurance, Demography
Abstract: Background/Purpose Formerly, Taiwan's diabetic population has been estimated by surveys conducted at irregular intervals and using different sampling methods. To obtain nationwide data on the incidence and prevalence of diabetes mellitus (DM) in Taiwan, we performed an analysis of the 2000–2009 claim data from the National Health Insurance (NHI) database. Methods One-third of the claims in the NHI database from 2000 to 2009 were randomly sampled. DM was defined by three or more outpatient visits with diagnostic codes (ICD-9-CM: 250 or A code: A181) within 1 year or by one inpatient discharge diagnosis of DM. Confirmation of type 1 diabetes mellitus was based on the issue of a catastrophic illness certificate with the same diagnostic codes. Age and/or gender distribution for DM were determined. Results In accordance with the global trend for DM, with a near constant standardized incidence rate, there was a more than 70% increase in the total diabetic population, or a 35% increase in the standardized prevalence rate, in Taiwan from 2000 to 2009. The incidence of diabetes was higher in men, especially in the 20–59-year-old age group, and the total number of men with diabetes exceeded the number of women with diabetes in 2005. However, the prevalence and incidence rates in women over the age of 60 years were higher than those in men. Type 1 DM was present in less than 1% of the diabetic population in Taiwan. Conclusion The incidence of diabetes, including type 1, remained stable over this 10-year period in Taiwan. However, the incidence rate in men aged 20–59 years was higher than that in age-matched women. With our nationwide database, subgroup analysis of DM incidence can be performed to refine our health policies for the prevention, screening, and treatment of diabetes mellitus.
Published: 2012

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