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1. Study design and recruitment for a prospective controlled study of diabesity: Taiwan Diabesity Study

Author: Wei-Jei Lee, Yi-Cheng Chang, Owaid Almalki, Seh-Huang Chao, Chieh Hsiang Lu, Ching-Chu Chen, Yu-Yao Huang, Yi-Chih Lee, and Chih-Cheng Hsu
Subjects: Surgery, RD1-811
Abstract: Summary: Background: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment. Methods: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years. Results: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group. Conclusion: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment. Keywords: Type 2 diabetes mellitus, Obesity, Diabesity, Metabolic surgery, Bariatric surgery, Recruitment
Published: 2019
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2. Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry

Author: Yun-Kai Yeh, Kuan-Hung Lin, Wayne Huey-Herng Sheu, Su-Huey Lo, Yen-Po Yeh, Chien-Ning Huang, Chii-Min Hwu, and Chieh-Hsiang Lu
Subjects: Type 2 diabetes, Early chronic kidney disease, Taiwan diabetes registry, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry. Materials and methods Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR. Results Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122–1.316), systolic blood pressure (OR 1.203, 95% CI 1.117–1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023–1.129) and triglyceride (OR 2.18, 95% CI 1.485–3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found. Conclusions We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.
Published: 2024
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3. A randomized trial on the effect of transcutaneous electrical nerve stimulator on glycemic control in patients with type 2 diabetes

Author: Jin-Ying Lu, Horng-Yih Ou, Chung-Ze Wu, Chwen-Yi Yang, Ju-Ying Jiang, Chieh-Hsiang Lu, Yi-Der Jiang, Tien-Jyun Chang, Yi-Cheng Chang, Meng-Lun Hsieh, Wan-Chen Wu, Hung-Yuan Li, Ye-Fong Du, Ching-Han Lin, Hao-Chang Hung, Kai-Jen Tien, Nai-Cheng Yeh, Shang-Yu Lee, Hui-I. Yu, and Lee-Ming Chuang
Subjects: Medicine, Science
Abstract: Abstract Transcutaneous electrical nerve stimulator (TENS) has been demonstrated to be beneficial in glycemic control in animal models, but its application in humans has not been well studied. We randomly assigned 160 patients with type 2 diabetes on oral antidiabetic drugs 1:1 to the TENS study device (n = 81) and placebo (n = 79). 147 (92%) randomized participants (mean [SD] age 59 [10] years, 92 men [58%], mean [SD] baseline HbA1c level 8.1% [0.6%]) completed the trial. At week 20, HbA1c decreased from 8.1% to 7.9% in the TENS group (− 0.2% [95% CI − 0.4% to − 0.1%]) and from 8.1% to 7.8% in the placebo group (− 0.3% [95% CI − 0.5% to − 0.2%]) (P = 0.821). Glycemic variability, measured as mean amplitude of glycemic excursion (MAGE) at week 20 were significantly different in the TENS group vs. the placebo group (66 mg/dL [95% CI 58, 73] vs. 79 mg/dL [95% CI 72, 87]) (P = 0.009). Our study provides the clinical evidence for the first time in humans that TENS does not demonstrate a statistically significant HbA1c reduction. However, it is a safe complementary therapy to improve MAGE in patients with type 2 diabetes.
Published: 2023
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4. Safety and efficacy of twice-daily exenatide in Taiwanese patients with inadequately controlled type 2 diabetes mellitus

Author: Chieh-Hsiang Lu, Ta-Jen Wu, Kuang-Chung Shih, Ewan Ni, Victoria Reed, Maria Yu, Wayne H.-H. Sheu, and Lee-Ming Chuang
Subjects: glucagon-like peptide 1, Taiwan, type 2 diabetes mellitus, Medicine (General), R5-920
Abstract: Exenatide has been predominantly studied in non-Asian populations. The purpose of this study was to investigate the safety and efficacy of twice-daily (BID) exenatide versus placebo in a subpopulation of Taiwanese patients from a larger study on Asian patients. Methods: Patients unable to achieve glycemic control with metformin alone or metformin in combination with sulfonylurea were randomly assigned to self-administer either 5 μg exenatide or placebo BID for 4 weeks, then 10 μg exenatide or placebo BID for an additional 12 weeks, in addition to their regular oral therapy. Results: Fifty patients from Taiwan were enrolled in this study (54.0% male; age: 50.9±9.4 years; weight: 71.0±11.6 kg; 8.1±1.0% hemoglobin A1c (HbA1c)). The exenatide-treated patients demonstrated a statistically significant greater reduction in HbA1c from baseline to the endpoint (least-squares [LS] mean [95% confidence interval (CI)]: -0.8% [-1.4–-0.2]; p=0.009) compared with patients who received placebo (LS mean [95% CI]: -0.1% [-0.7–0.4]) with an LS mean [95% CI] between-group difference of -0.7% (-1.3–-0.1) (p=0.025). A statistically significant higher number of exenatide-treated patients achieved HbA1c targets of ≤ 7% (p=0.020) and ≤ 6.5% (p=0.021) by the endpoint compared with patients who received placebo. Exenatide-treated patients experienced a statistically significant reduction in weight from baseline to endpoint (exenatide-placebo adjusted mean difference [95% CI]: -1.6 kg [-2.7–-0.6]; p=0.004) compared with the placebo group. The symptomatic hypoglycemia rate (mean patient/year±standard deviation) was higher in exenatide-treated patients (4.86 mean patient/year±7.36) than placebo-treated patients (0.27 mean patient/year±1.32). Thirteen (50.0%) exenatide-treated patients and nine (37.5%) placebo-treated patients reported one or more treatment-emergent adverse events; nausea was the most frequently reported side effect (exenatide, 4 [15.4%]; placebo, 0 [0.0%]). Conclusion: This subgroup analysis of Taiwanese patients was consistent with the overall study results, which showed that exenatide BID is superior to placebo for improving glycemic control in Asian patients with type 2 diabetes who experienced inadequate glycemic control when using oral antidiabetic therapy.
Published: 2013
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5. Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells

Author: Tsai-Sung Tai, Pei-Wen Zhao, Yun-Ping Lim, Ying-Ray Lee, Chieh-Hsiang Lu, Yi-Zhen Li, Yu-Pei Yen, Hui-I Yu, Shu-Hsin Chen, Yi-Sheng Zhang, Fang-Ping Kung, and Wen-Ying Chao
Subjects: Cancer Research, Cell cycle checkpoint, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cell cycle, medicine.disease, novel therapeutic strategy, Article, chemistry.chemical_compound, Oncology, chemistry, Apoptosis, recurrent thyroid cancer, Cancer cell, Cancer research, medicine, effective treatment, Anaplastic thyroid cancer, safe anticancer treatment, Protein kinase B, RC254-282, PI3K/AKT/mTOR pathway, Piperlongumine, anaplastic thyroid cancer
Abstract: Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper, it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL.
Published: 2021

6. Deep sea minerals ameliorate diabetic‐induced inflammation via inhibition of TNFα signaling pathways

Author: Hsiu I. Chen, Hsiu Chung Ou, Chieh Hsiang Lu, Cecilia Hsuan Day, Peiying Pai, Ruey Lin Chang, Vijaya Padmaviswanadha, Ray Jade Chen, Cheng Yu Lee, Dennis Jine Yuan Hsieh, and Chih Yang Huang
Subjects: Male, Diabetic Cardiomyopathies, Health, Toxicology and Mutagenesis, p38 mitogen-activated protein kinases, Anti-Inflammatory Agents, Inflammation, 010501 environmental sciences, Management, Monitoring, Policy and Law, Pharmacology, Toxicology, 01 natural sciences, Streptozocin, Diabetes Mellitus, Experimental, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Diabetic cardiomyopathy, medicine, Animals, Myocytes, Cardiac, Seawater, 0105 earth and related environmental sciences, Minerals, biology, Tumor Necrosis Factor-alpha, Chemistry, Kinase, Myocardium, General Medicine, medicine.disease, Streptozotocin, Rats, Nitric oxide synthase, Apoptosis, 030220 oncology & carcinogenesis, biology.protein, Cyclooxygenase, medicine.symptom, Signal Transduction, medicine.drug
Abstract: It has been well-documented that the consumption of deep sea water (DSW) has beneficial effects on myocardial hypertrophy and cardiac apoptosis induced by hypercholesterolemia. However, the molecular mechanisms for the anti-inflammatory effects of DSW on diabetic cardiomyopathy are still largely unclear. The main purpose of this present study was to test the hypothesis that DSW exerts anti-inflammatory effects through the suppression of the TNF-α-mediated signaling pathways. IP injection of streptozotocin (STZ) at the dose of 65 mg/kg was used to establish a diabetes rat model. DSW mineral extracts that diluted in desalinated water were prepared in three different dosages and administered to the rats through gavages for 4 weeks. These dosages are DSW-1X (equivalent to 37 mg Mg2+ /kg/day), 2X (equivalent to 74 mg Mg2+ /kg/day) and 3X (equivalent to 111 mg Mg2+ mg/kg/day). Immunofluorescence staining and Western blot showed that the protein expression level of TNF-α was markedly higher in the STZ-induced diabetic rat hearts than in the control group. Consequently, the phosphorylation levels of the TNF-α-modulated downstream signaling molecules and P38 mitogen-activated protein kinases (MAPKs) were notably elevated in heart tissues of STZ-induced diabetes. These higher phosphorylation levels subsequently upregulated NF-κB-modulated inflammatory mediators, such as cyclooxygenase (COX)-II and inducible nitric oxide synthase (iNOS). However, treatment with DSW as well as MgSO4 , the main mineral in DSW, significantly reversed all the alterations. These findings suggest that DSW has potential as a therapeutic agent for preventing diabetes-related cardiovascular diseases.
Published: 2019
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7. Deep ocean minerals inhibit IL-6 and IGFIIR hypertrophic signaling pathways to attenuate diabetes-induced hypertrophy in rat hearts

Author: Peiying Pai, Da Tong Ju, Chia Yao Shen, Vijaya Padma Viswanadha, Chieh Hsiang Lu, Hsiu Chung Ou, Chih Yang Huang, Cheng Yu Lee, Dennis Jine Yuan Hsieh, and Ruey Lin Chang
Subjects: Male, STAT3 Transcription Factor, 0301 basic medicine, Protein Kinase C-alpha, MAP Kinase Signaling System, Physiology, Apoptosis, Cardiomegaly, 030204 cardiovascular system & hematology, Receptor, IGF Type 2, Diabetes Mellitus, Experimental, Muscle hypertrophy, Rats, Sprague-Dawley, 03 medical and health sciences, Deep ocean minerals, 0302 clinical medicine, Physiology (medical), Diabetes mellitus, medicine, Animals, Eccentric, Interleukin 6, biology, Interleukin-6, Chemistry, Heart, medicine.disease, Rats, Cell biology, 030104 developmental biology, Cardiac hypertrophy, biology.protein, Signal transduction, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Signal Transduction
Abstract: We previously reported that deep sea water (DSW) prolongs the life span of streptozotocin (STZ)-induced diabetic rats by the compensatory augmentation of the insulin like growth factor (IGF)-I survival signaling and inhibition of apoptosis. Here, we investigated the effects of DSW on cardiac hypertrophy in diabetic rats. Cardiac hypertrophy was induced in rats by using STZ (65 mg/kg) administered via IP injection. DSW was prepared by mixing DSW mineral extracts and desalinated water. Different dosages of DSW-1X (equivalent to 37 mg Mg2+·kg−1·day−1), 2X (equivalent to 74 mg Mg2+·kg−1·day−1) and 3X (equivalent to 111 mg Mg2+·kg−1·day−1) were administered to the rats through gavage for 4 wk. Cardiac hypertrophy was evaluated by the heart weight-to-body weight ratio and the cardiac tissue cross-sectional area after hematoxylin and eosin staining. The protein levels of the cardiac hypertrophy signaling molecules were determined by Western blot. Our results showed that the suppressive effects of the DSW treatment on STZ-induced cardiac hypertrophy were comparable to those of MgSO4administration and that the hypertrophic marker brain natriuretic peptide (BNP) was decreased by DSW. In addition, DSW attenuated both the eccentric hypertrophy signaling pathway, IL-6-MEK-STAT3, and the concentric signaling pathway, IGF-II-PKCα-CaMKII, in DM rat hearts. The cardiac hypertrophy-associated activation of extracellular signal-regulated kinase (ERK) and the upregulation of the transcription factor GATA binding protein 4 (GATA4) were also negated by treatment with DSW. The results from this study suggest that DSW could be a potential therapeutic agent for the prevention and treatment of diabetic cardiac hypertrophy.NEW & NOTEWORTHY Deep sea water, containing high levels of minerals, improve cardiac hypertrophy in diabetic rats through attenuating the eccentric signaling pathway, IL-6-MEK5-STAT3, and concentric signaling pathway, IGF2-PKCα-CaMKII. The results from this study suggest that deep sea water could be a potential therapeutic agent for the prevention and treatment of diabetic cardiac hypertrophy.
Published: 2019
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8. Study design and recruitment for a prospective controlled study of diabesity: Taiwan Diabesity Study

Author: Yu-Yao Huang, Owaid M. Almalki, Ching-Chu Chen, Chih-Cheng Hsu, Wei-Jei Lee, Yi-Cheng Chang, Seh-Huang Chao, Chieh Hsiang Lu, and Yi-Chih Lee
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, End organ damage, Taiwan, lcsh:Surgery, Bariatric Surgery, Blood lipids, Overweight, Cohort Studies, Diabetes Complications, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Obesity, Prospective Studies, Prospective cohort study, Survival rate, Aged, business.industry, Type 2 Diabetes Mellitus, lcsh:RD1-811, Middle Aged, medicine.disease, Survival Rate, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Surgery, medicine.symptom, business, Body mass index, Follow-Up Studies
Abstract: Summary: Background: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment. Methods: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years. Results: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group. Conclusion: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment. Keywords: Type 2 diabetes mellitus, Obesity, Diabesity, Metabolic surgery, Bariatric surgery, Recruitment
Published: 2019
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9. How the impact of median neuropathy on sensorimotor control capability of hands for diabetes: an achievable assessment from functional perspectives.

Author: Haw-Yen Chiu, Hsiu-Yun Hsu, Li-Chieh Kuo, Fong-Chin Su, Hui-I Yu, Shih-Che Hua, and Chieh-Hsiang Lu
Subjects: Medicine, Science
Abstract: To comprehend the sensorimotor control ability in diabetic hands, this study investigated the sensation, motor function and precision pinch performances derived from a pinch-holding-up activity (PHUA) test of the hands of diabetic patients and healthy subjects. The precision, sensitivity and specificity of the PHUA test in the measurements of diabetic patients were also analyzed. We hypothesized that the diabetic hands would have impacts on the sensorimotor functions of the hand performances under functionally quantitative measurements. One hundred and fifty-nine patients with clinically defined diabetes mellitus (DM) and 95 age- and gender-matched healthy controls were included. Semmes-Weinstein monofilament (SWM), static and moving two-point discrimination (S2PD and M2PD), maximal pinch strength and precision pinch performance tests were conducted to evaluate the sensation, motor and sensorimotor status of the recruited hands. The results showed that there were significant differences (all p
Published: 2014
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10. 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

11. The Effects of Bariatric Surgery on Renal, Neurological, and Ophthalmic Complications in Patients with Type 2 Diabetes: the Taiwan Diabesity Study

Author: Keong Chong, Yi-Cheng Chang, Chih-Cheng Hsu, Seh-Huang Chao, Wei-Jei Lee, Yi-Chih Lee, Chieh-Hsiang Lu, Ching-Chu Chen, Meng-Lun Hsieh, Yu-Yao Huang, Lee-Ming Chuang, and Kong-Han Ser
Subjects: medicine.medical_specialty, Diabetic neuropathy, Visual acuity, Endocrinology, Diabetes and Metabolism, Original Contributions, Taiwan, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, Diabetic nephropathy, Overweight, Diabetic opthalmopathy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Bariatric surgery, Nutrition and Dietetics, business.industry, medicine.disease, Surgery, Obesity, Morbid, Diabetes Mellitus, Type 2, Albuminuria, medicine.symptom, business, Cohort study, Retinopathy
Abstract: Background Bariatric surgery has been shown to improve glycemic control in patients with type 2 diabetes. However, less is known whether it can also reduce diabetic renal, neurological, and ophthalmic complications. Methods This prospective multicenter cohort study compared renal, ophthalmic, and neurological complications between 49 patients with obesity/overweight receiving bariatric surgery and 338 patients receiving standard medical treatment after follow-up for 2 years. Patients received neurological examinations including toe tuning fork vibration test, ankle tendon reflex test, 10-g monofilament test, and ophthalmic examinations including visual acuity measurement and fundus examinations. Multiple regressions, propensity score weighting, and matching were employed to adjust for baseline differences. Results After 2 years of follow-up, patients with type 2 diabetes receiving bariatric surgery had greater reduction in BMI, HbA1c, and urine albumin–creatinine ratio, greater improvement in estimated glomerular filtration rate, and greater increase in tuning fork test score of right and left toes compared with the medical group. However, there is no improvement in 10 g-monofilament test, visual acuity, diabetic non-proliferative retinopathy, and proliferative retinopathy. Similar results were obtained using multiple regression adjustment, propensity-score weighting, or comparing age-, sex-, and BMI-matched subjects. Conclusions After 2-year follow-up, patients with obesity/overweight and type 2 diabetes receiving bariatric surgery have increased glomerular filtration rate, reduced albuminuria, and improved tuning folk vibration sensation.
Published: 2020

12. A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

Author: Fuu-Jen Tsai, Chi-Fan Yang, Ching-Chu Chen, Lee-Ming Chuang, Chieh-Hsiang Lu, Chwen-Tzuei Chang, Tzu-Yuan Wang, Rong-Hsing Chen, Chiung-Fang Shiu, Yi-Min Liu, Chih-Chun Chang, Pei Chen, Chien-Hsiun Chen, Cathy S J Fann, Yuan-Tsong Chen, and Jer-Yuarn Wu
Subjects: Genetics, QH426-470
Abstract: To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.
Published: 2010
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13. Lower risk of dementia with pioglitazone, compared with other second-line treatments, in metformin-based dual therapy: a population-based longitudinal study

Author: Chieh Hsiang Lu, Chen Yi Yang, Cheng Yang Hsieh, Huang Tz Ou, and Chung Yi Li
Subjects: Male, medicine.medical_specialty, endocrine system diseases, medicine.drug_class, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Lower risk, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Internal Medicine, Humans, Hypoglycemic Agents, Medicine, Dementia, Longitudinal Studies, Aged, Pioglitazone, business.industry, digestive, oral, and skin physiology, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, Sulfonylurea, Metformin, Drug Combinations, Thiazoles, Endocrinology, Diabetes Mellitus, Type 2, Female, Thiazolidinediones, business, Rosiglitazone, 030217 neurology & neurosurgery, medicine.drug
Abstract: The effect of pioglitazone was compared with that of other second-line glucose-lowering drugs on the risk of dementia among individuals with type 2 diabetes receiving metformin-based dual therapy. A total of 204,323 individuals with type 2 diabetes aged ≥18 years who were stable metformin users and dementia-free before the initiation of second-line glucose-lowering medication were identified in the period 2000–2011 from Taiwan’s National Health Insurance Research Database and followed to the end of 2013. Primary analyses included 51,415 individuals aged ≥65 years without dementia events in the first year of second-line glucose-lowering treatment. Study subjects were classified into mutually exclusive groups according to various second-line glucose-lowering drugs to metformin. Cox proportional hazards models were applied to assess the time-to-event between propensity score-matched glucose-lowering treatment groups. Individuals aged ≥65 years on metformin + pioglitazone had a significantly lower risk of dementia compared with those on metformin + sulfonylurea (HR 0.56; 95% CI 0.34, 0.93), and a lower, but insignificant, risk of dementia compared with those on other metformin-based dual regimens (i.e. metformin + acarbose, metformin + meglitinide, metformin + insulin or metformin + dipeptidyl peptidase 4 inhibitors). Among individuals aged ≥18 years, there was also a decreased risk of dementia in those taking pioglitazone compared with those taking other second-line glucose-lowering drugs. A lower incidence of dementia was found in users of metformin + pioglitazone compared with users of metformin + rosiglitazone. Pioglitazone as a second-line treatment after metformin might provide a protective effect on dementia risk among individuals with type 2 diabetes.
Published: 2017
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14. Do we underestimate influences of diabetic mononeuropathy or polyneuropathy on hand functional performance and life quality?

Author: Chieh Hsiang Lu, Yen Li Chao, Chien Ju Yang, Li-Chieh Kuo, Haw Yen Chiu, and Hsiu Yun Hsu
Subjects: Quality of life, Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Neural Conduction, 030209 endocrinology & metabolism, Type 2 diabetes, Motor Activity, Mononeuropathy, 03 medical and health sciences, 0302 clinical medicine, Physical medicine and rehabilitation, Diabetic Neuropathies, Diabetes mellitus, Internal Medicine, medicine, Humans, Purdue Pegboard Test, Hand function, 030212 general & internal medicine, Aged, business.industry, Diabetic mononeuropathy, Articles, General Medicine, Middle Aged, Hand, medicine.disease, Clinical Science and Care, Diabetes Mellitus, Type 2, Hand neuropathy, Physical therapy, Original Article, Female, Health education, business, Polyneuropathy
Abstract: Aims/Introduction The purpose of the present study was to identify whether there are differences in hand dexterity, hand functional performance and quality of life between diabetes patients with mononeuropathy and polyneuropathy of their hands to further present the importance regarding the impacts of diabetic neuropathic deficits on patients’ functional capacity. Materials and Methods The neurological deficits of 127 patients with type 2 diabetes were examined by electrophysiological tests for the median and ulnar nerves, and were stratified into the diabetic mononeuropathy, diabetic polyneuropathy and non-diabetic neuropathy groups by sensory amplitude of these nerves. The Purdue pegboard test, Michigan Hand Outcomes Questionnaire, and Diabetes-39 were carried out to understand patients’ hand dexterity, functional hand performance and quality of life, respectively. Results The results showed significant differences in all subtests of the Purdue pegboard test among the three groups. Furthermore, aesthetics, patient's satisfaction of the Michigan Hand Outcomes Questionnaire and diabetes control, sexual functioning, energy, and mobility of the Diabetes-39 also showed significant differences among the three groups. Conclusions The present study shows the patients with polyneuropathy suffer from more negative impacts on hand functional performance and quality of life than those with mononeuropathy and without neuropathy. These findings might assist both patients and clinicians in better realizing the impacts of neuropathic hands, and planning suitable strategies of intervention or health education to prevent declines in hand functions.
Published: 2017
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15. Autophagy Modulation in Human Thyroid Cancer Cells following Aloperine Treatment

Author: Chieh-Hsiang Lu, Chia-Yi Hou, Yun-Ping Lim, Hui-I Yu, Fang-Ping Kung, Ying-Ray Lee, Tsai-Sung Tai, Hsiang-Hsun Chuang, Hui-Ching Shen, and Shu-Hsin Chen
Subjects: autophagy, Quinolizidines, MAP Kinase Signaling System, Autophagic Cell Death, p38 mitogen-activated protein kinases, aloperine, medicine.disease_cause, Article, Catalysis, Inorganic Chemistry, lcsh:Chemistry, Piperidines, Cell Line, Tumor, thyroid cancer, Humans, Medicine, Thyroid Neoplasms, Physical and Theoretical Chemistry, Molecular Biology, Thyroid cancer, Protein kinase B, lcsh:QH301-705.5, Spectroscopy, business.industry, Akt/PKB signaling pathway, Organic Chemistry, Autophagy, Cell Cycle Checkpoints, General Medicine, medicine.disease, Neoplasm Proteins, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, Cancer cell, Cancer research, Signal transduction, business, Carcinogenesis
Abstract: Aloperine, an alkaloid isolated from Sophora alopecuroides, exhibits multiple pharmacological activities including anti-inflammatory, antioxidant, antiallergic, antinociceptive, antipathogenic, and antitumor effects. Furthermore, it exerts protective effects against renal and neuronal injuries. Several studies have reported antitumor effects of aloperine against various human cancers, including multiple myeloma, colon, breast, and prostate cancers, and osteosarcoma. Cell cycle arrest, apoptosis induction, and tumorigenesis suppression have been demonstrated following aloperine treatment. In a previous study, we demonstrated antitumor effects of aloperine on human thyroid cancer cells through anti-tumorigenesis and caspase-dependent apoptosis induction via the Akt signaling pathway. In the present study, we demonstrated the modulation of the autophagy mechanism following the incubation of multidrug-resistant papillary and anaplastic human thyroid cancer cells with aloperine, we also illustrate the underlying mechanisms, including AMPK, Erk, JNK, p38, and Akt signaling pathways. Further investigation revealed the involvement of the Akt signaling pathway in aloperine-modulated autophagy in human thyroid cancer cells. These results indicate a previously unappreciated function of aloperine in autophagy modulation in human thyroid cancer cells.
Published: 2019
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16. Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXR

Author: Yun-Ping Lim, Ying-Ray Lee, Ni Tien, Hui-I Yu, Chieh-Hsiang Lu, Fang-Yi Chu, Hsiao-Yun Chang, Hsiang-Hsun Chuang, Charles C.N. Wang, Hsin-Yi Shen, Tsai-Sung Tai, and Fang-Ping Kung
Subjects: 0303 health sciences, Pregnane X receptor, Article Subject, Liver X receptor alpha, lcsh:Other systems of medicine, lcsh:RZ201-999, digestive system, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, Transactivation, 0302 clinical medicine, Complementary and alternative medicine, Nuclear receptor, chemistry, Sesamin, 030220 oncology & carcinogenesis, Lipogenesis, polycyclic compounds, lipids (amino acids, peptides, and proteins), Liver X receptor, Protein kinase A, 030304 developmental biology, Research Article
Abstract: Liver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in many dietary plants and has a wide range of beneficial effects on metabolism. The mechanism underlying sesamin action especially on the regulation of LXR remains elusive. Reporter assays, mRNA and protein expression, and in silico modeling were used to identify sesamin as an antagonist of LXRα. Sesamin was applied to the hepatic HepaRG and intestinal LS174T cells and showed that it markedly ameliorated lipid accumulation in the HepaRG cells, by reducing LXRα transactivation, inhibiting the expression of downstream target genes. This effect was associated with the stimulation of AMP-activated protein kinase (AMPK) signaling pathway, followed by decreased T0901317-LXRα-induced expression of SREBP-1c and its downstream target genes. Mechanistically, sesamin reduced the recruitment of SRC-1 but enhanced that of SMILE to the SREBP-1c promoter region under T0901317 treatment. It regulated the transcriptional control exerted by LXRα by influencing its interaction with coregulators and thus decreased mRNA and protein levels of genes downstream of LXRα and reduced lipid accumulation in hepatic cells. Additionally, sesamin reduced valproate- and rifampin-induced LXRα and pregnane X receptor (PXR) transactivation. This was associated with reduced expression of target genes and decreased lipid accumulation. Thus, sesamin is an antagonist of LXRα and PXR and suggests that it may alleviate drug-induced lipogenesis via the suppression of LXRα and PXR signaling.
Published: 2019

17. 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 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, 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

18. 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

19. Diabetes pay-for-performance program can reduce all-cause mortality in patients with newly diagnosed type 2 diabetes mellitus

Author: Chin-Li Lu, Li-Chung Huang, Ching-Fang Tsai, Chieh-Hsiang Lu, and Fang-Ping Kung
Subjects: Adult, Male, medicine.medical_specialty, Taiwan, Observational Study, Comorbidity, Type 2 diabetes, Pay for performance, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, pay-for-performance program, Internal medicine, Diabetes mellitus, medicine, Humans, In patient, 030212 general & internal medicine, Reimbursement, Incentive, Aged, business.industry, Mortality rate, Hazard ratio, Disease Management, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Case-Control Studies, 030220 oncology & carcinogenesis, diabetes mellitus, Cohort, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, all-cause mortality, Patient Compliance, Female, business, Research Article
Abstract: Supplemental Digital Content is available in the text, This study aimed to examine the effect of a diabetes pay-for-performance (P4P) program on all-cause mortality in patients with newly diagnosed type 2 diabetes mellitus. Using a Taiwanese representative nationwide cohort, we recruited 5478 patients with newly diagnosed type 2 diabetes enrolled in the P4P program within 5 years after a diagnosis of diabetes between January 1, 2002 and December 31, 2010 and individuals not enrolled in the P4P program were recruited as the control group matched 1:1 with the study group. We used multivariate Cox proportional hazard models analysis to investigate the effect of the P4P program and adherence on all-cause mortality. A total of 250 patients died in the P4P group compared to 395 in the control group (mortality rate 104 vs 169 per 10,000 person-years, respectively, P
Published: 2020
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20. Proteomic analysis of honokiol-induced cytotoxicity in thyroid cancer cells

Author: Yi-Ting Tsai, Chieh-Hsiang Lu, Yi-Ching Su, Hui-I Yu, Ying-Ray Lee, Hong-Lin Chan, Hsiu-Chuan Chou, En-Chi Liao, Xin-Ru Yu, Yu-Shan Wei, Li-Hsun Lin, Hsiang-Hsun Chuang, Yi-Ting Yang, and Yu-An Chien
Subjects: 0301 basic medicine, Honokiol, Proteomics, Proteome, Cell Survival, Difference gel electrophoresis, Apoptosis, General Biochemistry, Genetics and Molecular Biology, Lignans, Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, Cell Line, Tumor, medicine, Humans, Glycolysis, Electrophoresis, Gel, Two-Dimensional, Thyroid Neoplasms, General Pharmacology, Toxicology and Pharmaceutics, Neoplasm Metastasis, Cytotoxicity, Thyroid cancer, Cytoskeleton, Plant Extracts, Gene Expression Profiling, Thyroid, Biphenyl Compounds, General Medicine, medicine.disease, Antineoplastic Agents, Phytogenic, Gene Expression Regulation, Neoplastic, 030104 developmental biology, medicine.anatomical_structure, chemistry, Magnolia, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Toxicity, Cancer research, Protein Processing, Post-Translational
Abstract: Aims Honokiol is a natural product extracted from herbal plants such as the Magnolia species which have been shown to exhibit anti-tumor and anti-metastatic properties. However, the effects of honokiol on thyroid cancers are largely unknown. Materials and methods To determine whether honokiol might be useful for the treatment of thyroid cancer and to elucidate the mechanism of toxicity of honokiol, we analyzed the impact of honokiol treatment on differential protein expression in human thyroid cancer cell line ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS). Key findings This study revealed 178 proteins that showed a significant change in expression levels and also revealed that honokiol-induced cytotoxicity in thyroid cancer cells involves dysregulation of cytoskeleton, protein folding, transcription control and glycolysis. Significance Our work shows that combined proteomic strategy provides a rapid method to study the molecular mechanisms of honokiol-induced cytotoxicity in thyroid cancer cells. The identified targets may be useful for further evaluation as potential targets in thyroid cancer therapy.
Published: 2018

21. Proteomic analysis of evodiamine-induced cytotoxicity in thyroid cancer cells

Author: Yi-Ting Tsai, Yu-Shan Wei, Hui-I Yu, Yi-Ting Yang, En-Chi Liao, Yi-Ching Su, Ying-Ray Lee, Hong-Lin Chan, Li-Hsun Lin, Hsiu-Chuan Chou, Chieh-Hsiang Lu, and Hsiang-Hsun Chuang
Subjects: 0301 basic medicine, Proteomics, Cell Survival, Difference gel electrophoresis, Clinical Biochemistry, Pharmaceutical Science, Analytical Chemistry, Two-Dimensional Difference Gel Electrophoresis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Evodiamine, Cell Line, Tumor, Drug Discovery, medicine, Cytotoxic T cell, Humans, Cytoskeleton, Cytotoxicity, Thyroid cancer, Spectroscopy, Thyroid, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cancer research, Quinazolines
Abstract: Evodiamine is a natural product extracted from herbal plants such as Tetradium which has shown to have anti-fat uptake and anti-proliferation properties. However, the effects of evodiamine on the behavior of thyroid cancers are largely unknown. To determine if evodiamine might be useful in the treatment of thyroid cancer and its cytotoxic mechanism, we analyzed the impact of evodiamine treatment on differential protein expression in human thyroid cancer cell line ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D-DIGE) combined with mass spectrometry (MS). This study demonstrated 77 protein features that were significantly changed in protein expression and revealed evodiamine-induced cytotoxicity in thyroid cancer cells involves dysregulation of protein folding, cytoskeleton, cytoskeleton regulation and transcription control. Our work shows that this combined proteomic strategy provides a rapid method to study the molecular mechanisms of evodiamine-induced cytotoxicity in thyroid cancer cells. The identified targets may be useful for further evaluation as potential targets in thyroid cancer therapy.
Published: 2018

22. Efficacy, safety, and tolerability of ipragliflozin in Asian patients with type 2 diabetes mellitus and inadequate glycemic control with metformin: Results of a phase 3 randomized, placebo‐controlled, double‐blind, multicenter trial

Author: Satoshi Yoshida, Satoshi Kokubo, Kyung Wan Min, Chieh-Hsiang Lu, Lee-Ming Chuang, and Bong Soo Cha
Subjects: Male, medicine.medical_specialty, Asia, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Thiophenes, 030204 cardiovascular system & hematology, Placebo, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Asian People, Double-Blind Method, Glucosides, Diabetes mellitus, Internal medicine, Multicenter trial, Type 2 diabetes mellitus, Internal Medicine, medicine, Humans, Glycemic, business.industry, Type 2 Diabetes Mellitus, General Medicine, Articles, medicine.disease, Clinical Trial, Metformin, Surgery, Ipragliflozin, Clinical Science and Care, Treatment Outcome, chemistry, Tolerability, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, business, medicine.drug
Abstract: Aims/Introduction To determine the efficacy and safety of ipragliflozin in combination with metformin in Asian patients with type 2 diabetes mellitus. Materials and Methods This phase 3, multicenter, placebo-controlled, double-blind, parallel-group study was carried out at 18 sites in Korea and 12 sites in Taiwan. After an 8-week washout period for patients using drugs other than metformin and a 2-week run-in period, patients were randomized to either 50 mg ipragliflozin or a placebo for 24 weeks while continuing metformin. Efficacy outcomes included the changes in hemoglobin A1c, fasting plasma glucose (FPG) and bodyweight from baseline to the end of treatment (with last observation carried forward). Safety outcomes included treatment-emergent adverse events. Results Between November 2011 and January 2013, 171 patients were randomized to and administered ipragliflozin (n = 87) or a placebo (n = 83). The mean changes (standard deviation) in hemoglobin A1c were −0.94% (0.75%) and −0.47% (0.81%) in the ipragliflozin and placebo groups, respectively (between-group difference −0.46%, P < 0.001). The changes in fasting plasma glucose and bodyweight were also significantly greater in the ipragliflozin group, with between-group differences of −14.1 mg/dL and −1.24 kg, respectively (both P < 0.001). The most common treatment-emergent adverse events (ipragliflozin vs placebo) were upper respiratory tract infection (9.2% vs 12.0%) and urinary tract infection (6.9% vs 2.4%). Conclusions These results show that ipragliflozin is effective and well tolerated when used in combination with metformin in Asian patients with type 2 diabetes mellitus.
Published: 2015

23. 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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24. Impacts of elevated glycaemic haemoglobin and disease duration on the sensorimotor control of hands in diabetes patients

Author: Fong-Chin Su, Chieh Hsiang Lu, Hwai-Ting Lin, Li-Chieh Kuo, Hsiu Yun Hsu, and Haw Yen Chiu
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Disease duration, Motor control, Disease, Pinch Strength, medicine.disease, Median nerve, Sensorimotor control, Endocrinology, Diabetes mellitus, Internal medicine, Sensation, Internal Medicine, Physical therapy, medicine, business
Abstract: Background To understand the impacts of disease chronicity and hyperglycaemia on sensorimotor control of hands of diabetic patients, this study investigated the differences in hand sensation, strength and motor control by applying the pinch-holding-up activity test for patients with diabetes mellitus (DM) with different levels of glycaemic control and disease chronicity. Methods One hundred and fifty-nine patients with clinically defined DM were included. Semmes–Weinstein monofilament, static two-point discrimination and moving two-point discrimination, maximal pinch strength precision pinch performance tests and nerve conduction studies (NCS) of the subjects were carried out. Forty-seven (29.6%) patients were in the HbA1c 7% group. There were 87 (54.7%) patients with the disease duration
Published: 2015
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25. Genome-Wide Association Study Meta-Analysis of Long Term Average Blood Pressure in East Asians

Author: Santhi K. Ganesh, E-Shyong Tai, Chieh Hsiang Lu, Jie Yao, Jia Yu Koh, Dongfeng Gu, Tanika N. Kelly, Tangchun Wu, Jer-Yuarn Wu, Neelam Kumari, DC Rao, Jinying Zhao, Sohee Han, Liang Sun, Xu Lin, Jerome I. Rotter, Ju Young Lee, Yun Kyoung Kim, Yao Hu, Walter Palmas, Meian He, Lixuan Gui, Kae-Woei Liang, Hua Hu, Chien-Hsiun Chen, Bong-Jo Kim, I-Te Lee, Xueling Sim, Rajkumar Dorajoo, Huaixing Li, Kent D. Taylor, Yik-Ying Teo, Jianjun Liu, Sanghoon Moon, Wayne H-H Sheu, Wen-Jane Lee, Bok-Ghee Han, Yingfeng Zheng, Yii-Der Ida Chen, Tien Yin Wong, Ching-Yu Cheng, Jiang He, Changwei Li, James E. Hixson, Yiqin Wang, Yunfeng He, Xiuqing Guo, Jing Chen, Leslie J. Raffel, and Fuu-Jen Tsai
Subjects: 0301 basic medicine, Male, Mean arterial pressure, Locus (genetics), Genome-wide association study, Blood Pressure, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, Asian People, Genetics, Humans, Gene, Genetics (clinical), Asia, Eastern, 030104 developmental biology, Blood pressure, Phenotype, CYP17A1, Genetic Loci, Meta-analysis, Female, ATP2B1, Cardiology and Cardiovascular Medicine, Genome-Wide Association Study
Abstract: Background— Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. Methods and Results— We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P −8 and 2.5×10 − 6 , respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P =5.03×10 − 8 , stage-2 P =8.64×10 − 3 , joint P =2.63×10 − 8 ) and mean arterial pressure (stage-1 P =3.59×10 − 9 , stage-2 P =2.35×10 − 2 , joint P =2.64×10 − 8 ). Three previously reported BP loci ( WBP1L , NT5C2 , and ATP2B1 ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P =8.55×10 − 6 , stage-2 P =1.62×10 − 5 , joint P =3.28×10 − 9 ) and mean arterial pressure (stage-1 P =9.19×10 − 7 , stage-2 P =9.69×10 − 5 , joint P =2.15×10 − 9 ) phenotypes. Fourteen genes ( TMEM180 , ACTR1A , SUFU , ARL3 , SFXN2 , WBP1L , CYP17A1 , C10orf32 , C10orf32 - ASMT , AS3MT , CNNM2 , and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes ( P =1.27×10 − 4 and 3.30×10 − 4 , respectively). Conclusions— We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
Published: 2017

26. Diabetes pay-for-performance program can reduce all-cause mortality in patients with newly diagnosed type 2 diabetes mellitus.

Author: Fang-Ping Kung, Ching-Fang Tsai, Chin-Li Lu, Li-Chung Huang, Chieh-Hsiang Lu, Kung, Fang-Ping, Tsai, Ching-Fang, Lu, Chin-Li, Huang, Li-Chung, and Lu, Chieh-Hsiang
Published: 2020
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27. Safety and efficacy of twice-daily exenatide in Taiwanese patients with inadequately controlled type 2 diabetes mellitus

Author: Ta-Jen Wu, Maria Yu, Chieh-Hsiang Lu, Victoria Reed, Ewan Ni, Lee-Ming Chuang, Wayne Huey-Herng Sheu, and Kuang-Chung Shih
Subjects: Adult, Male, medicine.medical_specialty, type 2 diabetes mellitus, Nausea, Taiwan, Type 2 diabetes, Placebo, Drug Administration Schedule, law.invention, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, Hypoglycemic Agents, Adverse effect, Aged, Glycemic, Medicine(all), Glycated Hemoglobin, lcsh:R5-920, Venoms, business.industry, General Medicine, Middle Aged, medicine.disease, glucagon-like peptide 1, Confidence interval, Surgery, Diabetes Mellitus, Type 2, Exenatide, Female, medicine.symptom, lcsh:Medicine (General), Peptides, business, medicine.drug
Abstract: Background/Purpose Exenatide has been predominantly studied in non-Asian populations. The purpose of this study was to investigate the safety and efficacy of twice-daily (BID) exenatide versus placebo in a subpopulation of Taiwanese patients from a larger study on Asian patients. Methods Patients unable to achieve glycemic control with metformin alone or metformin in combination with sulfonylurea were randomly assigned to self-administer either 5 μg exenatide or placebo BID for 4 weeks, then 10 μg exenatide or placebo BID for an additional 12 weeks, in addition to their regular oral therapy. Results Fifty patients from Taiwan were enrolled in this study (54.0% male; age: 50.9 ± 9.4 years; weight: 71.0 ± 11.6 kg; 8.1 ± 1.0% hemoglobin A1c (HbA1c)). The exenatide-treated patients demonstrated a statistically significant greater reduction in HbA1c from baseline to the endpoint (least-squares [LS] mean [95% confidence interval (CI)]: -0.8% [-1.4–-0.2]; p = 0.009) compared with patients who received placebo (LS mean [95% CI]: -0.1% [-0.7–0.4]) with an LS mean [95% CI] between-group difference of -0.7% (-1.3–-0.1) ( p = 0.025). A statistically significant higher number of exenatide-treated patients achieved HbA1c targets of ≤ 7% ( p = 0.020) and ≤ 6.5% ( p = 0.021) by the endpoint compared with patients who received placebo. Exenatide-treated patients experienced a statistically significant reduction in weight from baseline to endpoint (exenatide-placebo adjusted mean difference [95% CI]: -1.6 kg [-2.7–-0.6]; p = 0.004) compared with the placebo group. The symptomatic hypoglycemia rate (mean patient/year ± standard deviation) was higher in exenatide-treated patients (4.86 mean patient/year ± 7.36) than placebo-treated patients (0.27 mean patient/year ± 1.32). Thirteen (50.0%) exenatide-treated patients and nine (37.5%) placebo-treated patients reported one or more treatment-emergent adverse events; nausea was the most frequently reported side effect (exenatide, 4 [15.4%]; placebo, 0 [0.0%]). Conclusion This subgroup analysis of Taiwanese patients was consistent with the overall study results, which showed that exenatide BID is superior to placebo for improving glycemic control in Asian patients with type 2 diabetes who experienced inadequate glycemic control when using oral antidiabetic therapy.
Published: 2013
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28. Proteomic analysis of retinopathy-related plasma biomarkers in diabetic patients

Author: Chieh-Hsiang Lu, Szu-Ting Lin, Hsiu-Chuan Chou, Hong-Lin Chan, and Ying-Ray Lee
Subjects: Male, Protein-Arginine N-Methyltransferases, medicine.medical_specialty, Proteome, Biophysics, Serum Albumin, Human, Disease, Type 2 diabetes, Bioinformatics, Proteomics, Sensitivity and Specificity, Biochemistry, Internal medicine, Diabetes mellitus, medicine, Humans, Molecular Biology, Serum Albumin, Glycoproteins, Diabetic Retinopathy, business.industry, Reproducibility of Results, Diabetic retinopathy, Middle Aged, medicine.disease, Blood proteins, Endocrinology, Female, Carrier Proteins, business, Biomarkers, Retinopathy
Abstract: Diabetic retinopathy occurs in approximately 25% of patients with type 1 or type 2 diabetes; the disease can cause poor vision and even blindness because high glucose levels weaken retinal capillaries, causing leakage of blood into surrounding areas. We adopted a proteomics-based approach using 2D-DIGE and MALDI-TOF/TOF MS to compare the differential plasma proteome between diabetic retinopathy with significant retinopathy occurrence within 5 years after diagnosis of diabetes, and diabetic non-retinopathy without diagnosed retinopathy for more than 10 years after diagnosis of diabetes. We identified 77 plasma proteins, which represent 28 unique gene products. These proteins mainly have inflammatory response and coagulation roles. Our approach identified several potential diabetic retinopathy biomarkers including afamin and the protein arginine N-methyltransferase 5, which may be associated with the progression and development of diabetes. In conclusion, we report a comprehensive patient-based plasma proteomic approach to the identification of potential plasma biomarkers for diabetic retinopathy screening and detection.
Published: 2013
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29. Honokiol, a potential therapeutic agent, induces cell cycle arrest and program cell death in vitro and in vivo in human thyroid cancer cells

Author: Chieh-Hsiang Lu, Ying-Ray Lee, Yi-Wen Liu, Shu-Hsin Chen, Jin-Yi Wu, Yun-Ping Lim, Hui-I Yu, and Yi-Sheng Chang
Subjects: 0301 basic medicine, Honokiol, Programmed cell death, medicine.medical_specialty, Cell cycle checkpoint, Cell Survival, Apoptosis, Lignans, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Cell Line, Tumor, Autophagy, Medicine, Humans, Thyroid Neoplasms, Thyroid cancer, PI3K/AKT/mTOR pathway, Cell Proliferation, Pharmacology, business.industry, Cell growth, Biphenyl Compounds, Cell Cycle Checkpoints, Cell cycle, medicine.disease, Antineoplastic Agents, Phytogenic, 030104 developmental biology, Endocrinology, chemistry, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, business, Signal Transduction
Abstract: Thyroid cancer is the most common endocrine malignancy, the global incidence rate of which is rapidly rising. Surgery and radioiodine therapies are common and effective treatments only for nonmetastasized primary tumors. Therefore, effective treatment modalities are imperative for patients with radioiodine-resistant thyroid cancer. Honokiol, a biophenolic compound derived from Magnolia spp., has been shown have diverse biological and pharmacological activities, including anti-inflammatory, antioxidative, antiangiogenic, and anticancer properties. In the present study, three human thyroid cancer cell lines, namely anaplastic, follicular, and poorly differentiated thyroid cancer cells, were used to evaluate the chemotherapeutic activity of honokiol. Cell viability, cell cycle, apoptosis, and autophagy induction were determined through flow cytometry and western blot analysis. We found that honokiol treatment can suppress cell growth, induce cell cycle arrest, and enhance the induction of caspase-dependent apoptosis and autophagy in cancer cells. Moreover, honokiol treatment modulated signaling pathways including Akt/mTOR, ERK, JNK, and p38 in the studied cells. In addition, the antitumorigenic activity of honokiol was also confirmed in vitro and in vivo. Our data provide evidence that honokiol has a unique application in chemotherapy for human thyroid cancers.
Published: 2016

30. Piperlongumine Suppresses Proliferation of Human Oral Squamous Cell Carcinoma through Cell Cycle Arrest, Apoptosis and Senescence

Author: Yun-Ping Lim, Ching-Yen Lin, San-Yuan Chen, Peng-Yeh Lai, Chung-Sheng Shi, Hau-Ren Chen, Ying-Ray Lee, Geng-Hung Liu, Chieh-Hsiang Lu, and Wen-Ying Chao
Subjects: 0301 basic medicine, Cell cycle checkpoint, senescence, lcsh:Chemistry, chemistry.chemical_compound, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, Cellular Senescence, Mouth neoplasm, Caspase 3, apoptosis, Dioxolanes, General Medicine, Cell cycle, Computer Science Applications, Cell biology, human oral squamous cell carcinoma, cell cycle arrest, 030220 oncology & carcinogenesis, Carcinoma, Squamous Cell, Mouth Neoplasms, Cell aging, Senescence, Cyclin-Dependent Kinase Inhibitor p21, piperlongumine, Antineoplastic Agents, DNA Fragmentation, Biology, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Cell Line, Tumor, Humans, Physical and Theoretical Chemistry, Molecular Biology, Piperlongumine, Cell Proliferation, Cell growth, Organic Chemistry, Cell Cycle Checkpoints, Acetylcysteine, stomatognathic diseases, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, Apoptosis, Cancer research, Reactive Oxygen Species
Abstract: Oral squamous cell carcinoma (OSCC), an aggressive cancer originating in the oral cavity, is one of the leading causes of cancer deaths in males worldwide. This study investigated the antitumor activity and mechanisms of piperlongumine (PL), a natural compound isolated from Piper longum L., in human OSCC cells. The effects of PL on cell proliferation, the cell cycle, apoptosis, senescence and reactive oxygen species (ROS) levels in human OSCC cells were investigated. PL effectively inhibited cell growth, caused cell cycle arrest and induced apoptosis and senescence in OSCC cells. Moreover, PL-mediated anti-human OSCC behavior was inhibited by an ROS scavenger N-acetyl-l-cysteine (NAC) treatment, suggesting that regulation of ROS was involved in the mechanism of the anticancer activity of PL. These findings suggest that PL suppresses tumor growth by regulating the cell cycle and inducing apoptosis and senescence and is a potential chemotherapy agent for human OSCC cells.
Published: 2016

31. Pharmacogenetics of dipeptidyl peptidase 4 inhibitors in a Taiwanese population with type 2 diabetes

Author: Jer-Yuarn Wu, I-Te Lee, Wen-Jane Lee, Wayne H-H Sheu, Fuu Jen Tsai, Yi-Chun Chou, Chi-Fan Yang, Chung Hsing Wang, Ching-Chu Chen, Wen-Ling Liao, Chieh Hsiang Lu, and Chien-Hsiun Chen
Subjects: 0301 basic medicine, Gerontology, Adult, Male, medicine.medical_specialty, Genotype, Population, Drug Resistance, Taiwan, 030209 endocrinology & metabolism, Traditional Chinese medicine, Type 2 diabetes, Polymorphism, Single Nucleotide, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Asian People, DPP-4 inhibitors, Medicine, Humans, Hypoglycemic Agents, China, education, Protein Kinase C, Aged, Retrospective Studies, pharmacogenetics, education.field_of_study, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Taiwanese, Middle Aged, University hospital, medicine.disease, humanities, Pharmacogenomic Testing, 030104 developmental biology, Oncology, Diabetes Mellitus, Type 2, Medical genetics, Female, Personalized medicine, type 2 diabetes, business, Pharmacogenetics, Genome-Wide Association Study, Research Paper
Abstract: // Wen-Ling Liao 1, 2, * , Wen-Jane Lee 3, * , Ching-Chu Chen 4, 5, * , Chieh Hsiang Lu 6, 7, 8, * , Chien-Hsiun Chen 5, 9 , Yi-Chun Chou 9 , I-Te Lee 10, 11, 12 , Wayne H-H Sheu 10, 12, 13, 14 , Jer-Yuarn Wu 5, 9 , Chi-Fan Yang 9 , Chung-Hsing Wang 15, 16 , Fuu-Jen Tsai 5, 17, 18 1 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan 2 Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan 3 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan 4 Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan 5 School of Chinese Medicine, China Medical University, Taichung, Taiwan 6 Department of Internal Medicine, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi City, Taiwan 7 Department of Nursing, College of Nursing and Health Sciences, DAYEH University, Changhua, Taiwan 8 Department of Business management, College of Management, National Chung Cheng University, Chia-yi, Taiwan 9 National Center for Genome Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 10 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans Hospital, Taichung, Taiwan 11 School of Medicine, Chung Shan Medical University, Taichung, Taiwan 12 School of Medicine, National Yang-Ming University, Taipei, Taiwan 13 School of Medicine, National Defense Medical Center, Taipei, Taiwan 14 Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan 15 Department of Genetics and Metabolism, Children’s Hospital of China Medical University, Taichung, Taiwan 16 School of Medicine, China Medical University, Taichung, Taiwan 17 Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan 18 Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan * These authors have contributed equally to this work Correspondence to: Fuu-Jen Tsai, email: d0704@www.cmuh.org.tw Keywords: DPP-4 inhibitors, pharmacogenetics, Taiwanese, type 2 diabetes Received: January 29, 2016 Accepted: January 03, 2017 Published: February 01, 2017 ABSTRACT Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes ( T2D ). Despite DPP-4 inhibitors’ advantages, the patients’ therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors ( P < 1 × 10 -4 ) were identified at or near PRKD1 , CNTN3 , ASK, and LOC10537792. A SNP located within the fourth intron of PRKD1 (rs57803087) was strongly associated with DPP-4 inhibitor response ( P = 3.2 × 10 -6 ). This is the first pharmacogenomics study on DPP-4 inhibitor treatment for diabetes in a Taiwanese population. Our data suggest that genes associated with β-cell function and apoptosis are involved in the therapeutic effect of DPP-4 inhibitors, even in the presence of additional oral anti-diabetic drugs. Our findings provide information on how genetic variants influence drug response and may benefit the development of personalized medicine.
Published: 2016

32. Sacroiliitis-like pain as the initial presentation of primary hyperparathyroidism

Author: Hui-I Yu and Chieh-Hsiang Lu
Subjects: Adult, medicine.medical_specialty, endocrine system diseases, Bone disease, Osteoporosis, Population, Osteitis fibrosa cystica, Diagnosis, Differential, medicine, Humans, Orthopedics and Sports Medicine, Sacroiliitis, Radionuclide Imaging, education, Hyperparathyroidism, education.field_of_study, business.industry, Hyperparathyroidism, Primary, medicine.disease, Arthralgia, Magnetic Resonance Imaging, Low back pain, Surgery, Vietnam, Female, Radiology, medicine.symptom, Tomography, X-Ray Computed, business, Low Back Pain, Primary hyperparathyroidism
Abstract: Hyperparathyroidism often presents with asymptomatic hypercalcemia or minimal, unspecific symptoms and the middle-age female is the predominant population. We reported a young Vietnamese female with primary hyperparathyroidism presented with chronic low back pain of about 1 year duration, similar to sacroiliitis. An initial study of bone scan raised the suspicion of sacroiliitis. However, careful review of her symptoms and signs did not demonstrate the presence of typical inflammatory low back pain instead of severe osteoporosis and osteitis fibrosa cystica. A computed tomography of pelvis showed subchondral bony resorption or erosive change with bilateral SI joint widening which more favored hyperparathyroidism than sacroiliitis. This case highlights the point that primary hyperparathyroidism could be presented with sacroiliitis-like pain and severe bone disease in young patient from a developing country.
Published: 2012
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33. Evodiamine inhibits human thyroid cancer cells in vitro and in vivo

Author: Chieh-Hsiang Lu, Yi-Wen Liu, Ying-Ray Lee, Yi-Sheng Chang, and Shu-Hsin Chen
Subjects: Cell cycle checkpoint, business.industry, Thyroid, Cancer, medicine.disease, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Apoptosis, Evodiamine, Cancer cell, medicine, Cancer research, Anaplastic thyroid cancer, business, Thyroid cancer
Abstract: Introduction: Thyroid cancer is the most prevalent cancer among endocrine malignancies. In clinically, surgical resection combined with radioactive iodine therapy has been proved effective in treating differentiated thyroid cancer, including papillary and follicular thyroid cancers (FTC). However, patients with incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) exhibit worse prognosis. Therefore, a novel and effective treatment is urgently needed to deal with the current treatment. Evodiamine is one of the important components isolated from Chinese herb Wu-Chu-Yu, and has been demonstrated to contribute on anti-inflammatory effects, anti-angiogenesis, anti-tumor growth, anti-invasive and metastatic activities, and up-regulating apoptosis. In the present study, we examined the effects of evodiamine in FTC, PDTC and ATC cells, respectively. Evodiamine inhibited cellular proliferation and the colonies formation of FTC, PDTC and ATC cells. Cell cycle arrest at G2/M phase was found in all of the cells during evodiamine treatment. Moreover, caspase-dependent apoptosis in these cells was also revealed under evodiamine treatment. In addition, autophagy induction was also found in evodiamine treated human thyroid cancer cells. Finally, we verified the effects of evodiamine on anti-human thyroid cancers in a xenograft nude mice model. Our results demonstrate that evodiamine induces cell cycle arrest, caspase-dependent apoptosis and autophagy leading to inhibit proliferation of multiple types of human thyroid cancer cells. We suggest that evodiamine could be a chemo-therapeutic candidate for human thyroid cancers.
Published: 2015
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34. The correlation between health behavior and self-efficacy of obese diabetic patients

Author: Hsiang-Hsun Chuang and Chieh-Hsiang Lu
Subjects: Self-efficacy, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, General Medicine, medicine.disease, Correlation, Endocrinology, Diabetes mellitus, Internal Medicine, medicine, Physical therapy, Health behavior, business
Published: 2016
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35. Effect of bariatric surgery on diabetic complications: the Taiwan diabesity study

Author: Seh-Huang Chao, Yi-Cheng Chang, Ching-Chu Chen, Chieh Hsiang Lu, and Wei-Jei Lee
Subjects: medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes mellitus, Internal Medicine, medicine, General Medicine, medicine.disease, business, Surgery
Published: 2016
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36. The correlation between lifestyle factors and subclinical neuropathy in patients with type 2 diabetes

Author: Chieh-Hsiang Lu and Hsiang-Hsun Chuang
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, General Medicine, Type 2 diabetes, medicine.disease, Correlation, Endocrinology, Lifestyle factors, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, In patient, business, Subclinical infection
Published: 2016
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37. The investigation of mobile communication software 'Line' intervention for diabetes nutrition and health education

Author: Chieh-Hsiang Lu and Hsiang-Hsun Chuang
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, General Medicine, medicine.disease, Endocrinology, Software, Nursing, Diabetes mellitus, Intervention (counseling), Internal Medicine, medicine, Physical therapy, Health education, Mobile telephony, Line (text file), business
Published: 2016
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38. Impacts of elevated glycaemic haemoglobin and disease duration on the sensorimotor control of hands in diabetes patients

Author: Hsiu-Yun, Hsu, Haw-Yen, Chiu, Hwai-Ting, Lin, Fong-Chin, Su, Chieh-Hsiang, Lu, and Li-Chieh, Kuo
Subjects: Glycated Hemoglobin, Male, Hand Strength, Median Neuropathy, Neural Conduction, Taiwan, Middle Aged, Hand, Severity of Illness Index, Up-Regulation, Diabetic Neuropathies, Feedback, Sensory, Motor Skills, Risk Factors, Hyperglycemia, Diabetes Mellitus, Humans, Pinch Strength, Female, Prospective Studies, Aged
Abstract: To understand the impacts of disease chronicity and hyperglycaemia on sensorimotor control of hands of diabetic patients, this study investigated the differences in hand sensation, strength and motor control by applying the pinch-holding-up activity test for patients with diabetes mellitus (DM) with different levels of glycaemic control and disease chronicity.One hundred and fifty-nine patients with clinically defined DM were included. Semmes-Weinstein monofilament, static two-point discrimination and moving two-point discrimination, maximal pinch strength precision pinch performance tests and nerve conduction studies (NCS) of the subjects were carried out. Forty-seven (29.6%) patients were in the HbA(1c) 7% category, and 112 (70.4%) patients were in the7% group. There were 87 (54.7%) patients with the disease duration10 years, and 72 (45.3%) patients with disease duration ≧10 years.The severity of hyperglycaemia significantly impacts the results for Semmes-Weinstein monofilament, precision pinch force control, sensory and motor NCS tests (p 0.05). In addition, the chronicity of disease influences the motor control of precision pinch performance and the amplitude of motor NCS (p 0.05) for the diabetes patients.The evidence suggests that disease chronicity and hyperglycaemia have impacts on sensorimotor control in the hands of DM patients. In addition, the efficiency of prehensile forces of hand-to-object interactions in the pinch-holding-up activity test could be significant for identifying hand function, as well as pathologic changes in median nerve function, for patients with DM.
Published: 2014

39. The associations among hand dexterity, functional performance, and quality of life in diabetic patients with neuropathic hand from objective- and patient-perceived measurements

Author: Li-Chieh Kuo, Chieh Hsiang Lu, Yen Li Chao, Hsiu Yun Hsu, Chien Ju Yang, and Haw Yen Chiu
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, Affect (psychology), Diagnostic Self Evaluation, Disability Evaluation, Young Adult, Physical medicine and rehabilitation, Quality of life, Diabetic Neuropathies, Diabetes mellitus, medicine, Purdue Pegboard Test, Humans, Young adult, Aged, Glycated Hemoglobin, business.industry, Public Health, Environmental and Occupational Health, Middle Aged, medicine.disease, Hand, Median nerve, Physical therapy, Quality of Life, Anxiety, Observational study, Female, Self Report, medicine.symptom, business
Abstract: To comprehend the associations among the dexterity and functional performance of the hands and quality of life in diabetic patients with neuropathic hands, via objective- and patient-perceived measurements. The study participants were 144 diabetes patients who received objective evaluations, including the Purdue pegboard test, electrophysiological testing in sensory amplitude of the median nerve, and self-administrated measurements, including the Michigan Hand Outcomes Questionnaire (MHQ) and Diabetes-39 (D-39). Pearson’s and Spearman’s correlation tests were conducted to assess the relationships among hand neuropathy, hand dexterity and functions, and quality of life. The results show that the amplitude of the sensory nerve action potential of the median nerve was positively correlated with hand dexterity (r = 0.28–0.43; p
Published: 2014

40. Anti-proliferative effects of evodiamine on human thyroid cancer cells

Author: Chieh-Hsiang Lu, Ying-Ray Lee, Yi-Sheng Chang, and Yi-Wen Liu
Subjects: chemistry.chemical_compound, chemistry, Evodiamine, business.industry, Cancer cell, Cancer research, Medicine, Human thyroid, Anti proliferative, business
Published: 2014
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41. Association of TLR7 and TSHR copy number variation with Graves’ disease and Graves’ ophthalmopathy in Chinese population in Taiwan

Author: Wen Ling Liao, Ching-Chu Chen, Chieh Hsiang Lu, Siu San Tse, Lei Wan, Tzu-Yuan Wang, and Fuu Jen Tsai
Subjects: Adult, Male, medicine.medical_specialty, DNA Copy Number Variations, Graves' disease, Taiwan, Disease, Real-Time Polymerase Chain Reaction, Graves' ophthalmopathy, Disease susceptibility, Asian People, Gene Frequency, Risk Factors, Graves’ ophthalmopathy, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Copy-number variation, TLR7, Chinese population, Copy number variation, business.industry, Receptors, Thyrotropin, General Medicine, TSHR, medicine.disease, Graves Disease, eye diseases, Graves Ophthalmopathy, Ophthalmology, Logistic Models, Endocrinology, Toll-Like Receptor 7, Case-Control Studies, Immunology, Female, Graves’ disease, business, Research Article
Abstract: Background Graves’ disease (GD) and Graves’ ophthalmopathy (GO) are autoimmune disorders, which might be influenced by genetic factors. Copy number variation (CNV) is an important source of genomic diversity in humans, and influences disease susceptibility. This study investigated the association between CNV in the TSHR and TLR7 genes and the development of GD and GO in a Chinese population in Taiwan. Methods For this case-control study, sample from 196 healthy controls and 484 GD patients, including 203 patients with GO were studied. CNV was detected by real-time polymerase chain reaction (PCR) using TaqMan™ probes and the relative copy number (CN) was estimated by using the comparative Ct method. Results The differences in the distribution of TSHR CNV in healthy controls and GD patients were statistically significant (p value = 0.01). However, the difference in the distribution of TSHR CNV in the control group and the GO group was not statistically significant (p value = 0.06). For TLR7 CNV, the results were not significantly different when we compared the distribution in healthy controls and GD patients and in healthy controls and GO patients (p values for Fisher’s exact test were 0.13 and 0.09, respectively). However, a lower than normal CNV for TLR7 (CNV Conclusions These results suggested that TSHR and TLR7 CNV might be associated with susceptibility to GD.
Published: 2014
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42. Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients

Author: Ching-Chu Chen, Wun Rong Lin, Yu Chuen Huang, Wen Ling Liao, Marcelo Chen, Chieh Hsiang Lu, and Fuu Jen Tsai
Subjects: Male, medicine.medical_specialty, China, Waist, Endocrinology, Diabetes and Metabolism, Taiwan, Type 2 diabetes, Polymorphism, Single Nucleotide, Severity of Illness Index, Retina, Endocrinology, Asian People, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, Aged, Diabetic Retinopathy, business.industry, Chimerin Proteins, Diabetic retinopathy, Odds ratio, Chimerin 2, Middle Aged, medicine.disease, Blood pressure, Cross-Sectional Studies, Logistic Models, Diabetes Mellitus, Type 2, Case-Control Studies, Female, business, Body mass index
Abstract: Aim To investigate whether chimerin 2 ( CHN2) genetic polymorphisms were associated with the susceptibility to diabetic retinopathy (DR) in Taiwanese individuals with type 2 diabetes. Methods This case-control study comprised of 171 individuals with DR and 548 without DR. Four rs39059, rs2023908, rs1002630 and rs1362363 polymorphism of CHN2 were genotyped for each subjects. All subjects underwent a complete ophthalmologic examination, and basic information (age, gender, age at diagnosis of diabetes, and ocular history of the patient) was record. Several clinical parameters (systolic and diastolic blood pressure, waist and hip circumferences, body mass index levels, fasting glucose and HbA1c) were measured. Results Logistic regressions were used to analyze odds ratios between SNPs and DR after controlling for gender, systolic blood pressure, waist and hip ratio, duration of diabetes, serum HbA1c levels and nephropathy classification. A protective effect of rs1002630 (GA+AA) and rs1362363 (AG+GG) [odds ratio (OR) (95% confidence interval)=0.45 (0.22–0.88), 0.66 (0.44–0.99), respectively) was observed. Furthermore, the protective effect of rs1002630 was observed when compared subjects with non-proliferative DR with subjects without DR [OR=0.25 (95%C.I. = 0.09–0.73)]. Conclusions This study showed that the rs1002630 of CHN2 were associated with DR risk and non-proliferative DR risk in Taiwanese individuals with type 2 diabetes. Variations at this locus may contribute to the pathogenesis of DR.
Published: 2013

43. Identification of plasma biomarkers in human diabetic retinopathy

Author: Hong-Lin Chan, Ying-Ray Lee, and Chieh-Hsiang Lu
Subjects: business.industry, Medicine, Identification (biology), Diabetic retinopathy, Plasma biomarkers, Bioinformatics, business, medicine.disease
Published: 2013
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44. Effectiveness of diabetes quality improvement program in Chia-yi region of Taiwan

Author: Chieh-Hsiang Lu, Hsiang-Hsun Chuang, and Cheng-Ren Chen
Subjects: medicine.medical_specialty, Endocrinology, Quality management, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes mellitus, Internal Medicine, Physical therapy, medicine, General Medicine, medicine.disease, business
Published: 2016
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45. Gender difference on the eating styles and the effect of group diet education in adolescents in Taiwan

Author: Hsiang-Hsun Chuang and Chieh-hsiang Lu
Subjects: Endocrinology, business.industry, Group (periodic table), Endocrinology, Diabetes and Metabolism, Diabetes mellitus, Internal Medicine, Medicine, General Medicine, business, medicine.disease, Clinical psychology
Published: 2016
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46. Autophagy induction of reversine on human follicular thyroid cancer cells

Author: Shih-Che Hua, Ying-Ray Lee, Yi-Wen Liu, Hui-I Yu, Chieh-Hsiang Lu, and Yi-Ping Chang
Subjects: medicine.medical_specialty, Programmed cell death, Morpholines, Blotting, Western, Cell Culture Techniques, Antineoplastic Agents, Biology, chemistry.chemical_compound, Internal medicine, Cell Line, Tumor, Adenocarcinoma, Follicular, medicine, Autophagy, Humans, Thyroid Neoplasms, Anaplastic thyroid cancer, Follicular thyroid cancer, Protein kinase B, Thyroid cancer, PI3K/AKT/mTOR pathway, Cell Proliferation, Pharmacology, Microscopy, Confocal, Dose-Response Relationship, Drug, TOR Serine-Threonine Kinases, General Medicine, medicine.disease, Endocrinology, chemistry, Purines, Cancer research, Microtubule-Associated Proteins, Proto-Oncogene Proteins c-akt, Reversine
Abstract: The incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are the most aggressive in all of the thyroid cancers. Unfortunately, there are almost no effective therapies. A novel and effective treatment is urgently needed to develop. Recently, reversine, a small synthetic purine analogue, has been reported to be effective in human thyroid cancer suppression through cell cycle arrest and apoptosis induction. In this study, we performed an in vitro evaluation of reversine on autophagy activation, one of the programmed cell death, and the related mechanisms in human follicular thyroid cancer cell line WRO. Incubation of WRO cells with reversine induced autophagosome formation in a short time treatment. LC3-II overexpression in a dosage-dependent manner with reversine treatment was demonstrated in the autophagy activation. Moreover, reversine suppressed Akt/mTOR related signaling pathway activation, a major pathway for autophagy activation, was also revealed in WRO cells. Our data demonstrated that reversine is effective to induce autophagy. Moreover, the LC3-II overexpression and the p62 protein were degraded in a time-dependent manner, indicating that the autophagic flux has happened in the reversine treated WRO cells. In addition, the activation of Akt/mTOR/p70S6K related pathways were shown to be reduced, suggesting these pathways may involve in the reversine mediated autophagy induction. Reversine is therefore worthy of further investigation in clinical therapeutics.
Published: 2012

47. Hemopexin is up-regulated in plasma from type 1 diabetes mellitus patients: Role of glucose-induced ROS

Author: Szu-Ting Lin, Chieh-Hsiang Lu, Ying-Chieh Lu, Hsiu-Chuan Chou, You-Hsuan Chen, John F. Timms, Hong-Lin Chan, Chia-Ching Chen, Ying-Ray Lee, Yi-Wen Chen, Yun-Ching Lee, and Wen-Li Lee
Subjects: Adolescent, Quantitative proteomics, Biophysics, medicine.disease_cause, Biochemistry, chemistry.chemical_compound, Downregulation and upregulation, Hemopexin, medicine, Humans, Child, Cells, Cultured, chemistry.chemical_classification, Reactive oxygen species, Glutathione, Blood Proteins, Blood proteins, Up-Regulation, body regions, Diabetes Mellitus, Type 1, Glucose, chemistry, Proteome, Reactive Oxygen Species, Oxidative stress, Biomarkers
Abstract: Type 1 diabetes mellitus (T1DM) is an insulin-dependent metabolic disease in the world and often occurs in children and adolescents. Recent advances in quantitative proteomics offer potential for the discovery of plasma proteins as biomarkers for tracking disease progression and for understanding the molecular mechanisms of diabetes. Comparative proteomic analysis of the plasma proteomes from T1DM cases and healthy donors with lysine- and cysteine-labeling 2D-DIGE combining MALDI–TOF/TOF mass spectrometry revealed that 39 identified T1DM-associated plasma proteins showed significant changes in protein expression including hemopexin, and 41 in thiol reactivity. Further study showed that hemopexin can be induced in numerous cell lines by increasing the glucose concentration in the medium. Interestingly, glucose-induced hemopexin expression can be reduced by reactive oxygen species (ROS) scavengers such as glutathione, implying that hemopexin expression is linked to glucose-induced oxidative stress. In conclusion, the current work has identified potential T1DM biomarkers and one of these, hemopexin, can be modulated by glucose through a ROS-dependent mechanism.
Published: 2012

48. Reversine, a 2,6-disubstituted purine, as an anti-cancer agent in differentiated and undifferentiated thyroid cancer cells

Author: Chieh-Hsiang Lu, Yi-Ping Chang, Tien-Chun Chang, Shu-Hsin Chen, Hau-Ren Chen, Ying-Ray Lee, Hui-I Yu, Shih-Che Hua, and Yi-Wen Liu
Subjects: Oncology, Purine, Male, endocrine system, medicine.medical_specialty, endocrine system diseases, Thyroid Gland, Pharmaceutical Science, Purine analogue, Mice, Nude, Antineoplastic Agents, Apoptosis, Thyroid Carcinoma, Anaplastic, chemistry.chemical_compound, Mice, Internal medicine, Cell Line, Tumor, medicine, Animals, Humans, Pharmacology (medical), Thyroid Neoplasms, Anaplastic thyroid cancer, Thyroid cancer, Cell Proliferation, Pharmacology, Caspase 8, Mice, Inbred BALB C, business.industry, Caspase 3, Organic Chemistry, Cell Cycle, Cancer, Cell cycle, medicine.disease, Caspase 9, chemistry, Purines, Molecular Medicine, business, Biotechnology, Reversine
Abstract: A novel and effective treatment is urgently needed to deal with the current treatment dilemma in incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC). Reversine, a small synthetic purine analogue (2,6-disubstituted purine), has been shown to be effective in tumor suppression.We performed in vitro evaluation of anti-tumor effects of reversine on proliferation, cell cycle, and apoptosis in human PDTC, ATC, and follicular thyroid cancer cell lines, respectively.Treatment of these three lines with reversine inhibited proliferation in a time- and dose-dependent manner. G2/M accumulation was demonstrated in cell cycle analysis. Reversine induced apoptosis in PDTC cells with caspase-3 and caspase-8 activation, but not caspase-9. Use of a pan-caspase inhibitor before treatment with reversine attenuated cell death. Reversine also showed in vivo growth inhibitory effects on ATC cells in a xenograft nude mice model.Data demonstrated that reversine is effective in inhibiting the growth of thyroid cancer cells by cell cycle arrest or apoptosis, especially with the more aggressive ATC and PDTC. Apoptosis was induced by the mitochondria-independent pathway. Reversine is therefore worthy of further investigation in clinical therapeutics.
Published: 2011

49. The effects of growth inhibitory peptide on follicular thyroid cancer cell growth, migration, and invasion

Author: Hui-I Yu, Tien-Chun Chang, Ping-Tzu Chen, Chieh-Hsiang Lu, Shih-Che Hua, Ying-Ray Lee, Syue-Yi Chen, and Yu-Ting Kao
Subjects: endocrine system, Cancer Research, medicine.medical_specialty, Cell Survival, Antineoplastic Agents, 030218 nuclear medicine & medical imaging, Metastasis, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Internal medicine, Adenocarcinoma, Follicular, medicine, Tumor Cells, Cultured, Humans, Neoplasm Invasiveness, Thyroid Neoplasms, Follicular thyroid cancer, Thyroid cancer, Cell growth, business.industry, Thyroid, Membrane Proteins, General Medicine, medicine.disease, Endocrinology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Endocrine neoplasm, Cancer research, Adenocarcinoma, business
Abstract: Aims and background Thyroid cancer is the most common endocrine neoplasm worldwide. Although differentiated thyroid cancers are associated with a favorable survival, the prognosis worsens dramatically for patients with distant metastasis. Metastases from follicular thyroid carcinoma (FTC) occur earlier and are more aggressive than those from papillary thyroid carcinoma. For FTC that is resistant to radioactive iodine, new treatments are urgently needed. Human alpha-fetoprotein (HAFP) is a tumor-associated fetal protein that has been demonstrated to regulate tumorigenesis. Growth inhibitory peptide (GIP), a synthetic 34-mer peptide isolated from the third domain of HAFP, has been shown to have antitumor growth ability in various human cancers. However, the effects of GIP in FTC have not yet been studied. The aim of this study was to investigate the antitumor ability of GIP in FTC. Methods and study design Using both PBS and GIP control peptide as a negative control, the antiproliferative activity of GIP in the WRO human FTC cell line was determined using a tetrazolium-based colorimetric assay. In addition, cell migration and invasion assays were used to measure tumor metastasis inhibition effects in vitro. Results GIP did not inhibit WRO cell proliferation in a time- or dose-dependent manner. However, in WRO cells treated with GIP for 4 days, migration was significantly inhibited at concentrations of 50 and 100 μM (33.3% and 19.5%, respectively; both P Conclusions Although GIP failed to suppress FTC cell growth, it effectively interrupted both FTC cell migration and invasion abilities in vitro. Further validation in an animal model and elucidation of the underlying mechanisms will be required. GIP may potentially serve as an anti-FTC metastasis agent aiding current chemotherapy regimens.
Published: 2010

50. Risperidone-associated newly diagnosed diabetes and fatal diabetes ketoacidosis in a young schizophrenic patient

Author: Yuan –Horng Yan and Chieh-Hsiang Lu
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Fatal outcome, Diabetic ketoacidosis, Endocrinology, Diabetes and Metabolism, Diabetic Ketoacidosis, Endocrinology, Fatal Outcome, Diabetes mellitus, Internal Medicine, medicine, Diabetes Mellitus, Humans, Psychiatry, Risperidone, business.industry, General Medicine, medicine.disease, Ketoacidosis, Newly diagnosed diabetes, Schizophrenia, Presentation (obstetrics), business, medicine.drug, Antipsychotic Agents
Abstract: A 27-year-old man, who has been using risperidone for two months as the treatment for schizophrenia, with no previous history of diabetes was admitted to the hospital with the presentation of severe diabetes ketoacidosis and subsequent fatal progression.
Published: 2008

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