143 results on '"Andreas Pfützner"'
Search Results
2. The Diabetes Technology Society Green Declaration
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Donna A. Seid, Kathleen Gold, David C. Klonoff, Andreas Pfützner, Edward Krisiunas, Laurence Bouret, Kevin T. Nguyen, Rick Bonilla, Ashley Y. DuBord, Nicole Y. Xu, Tobias Stumpe, Lutz Heinemann, Trisha Shang, Jennifer Y Zhang, and Weronika Burkot
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Technology ,Economic growth ,Endocrinology, Diabetes and Metabolism ,Circular economy ,Biomedical Engineering ,Declaration ,Bioengineering ,Solid Waste ,Commentaries ,Sustainability ,Diabetes Mellitus ,Internal Medicine ,Humans ,Recycling ,Business - Published
- 2021
3. Orale Immunkompetenz in der Corona-Pandemie vs. Systemrelevanz der Zahnmedizin
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Roland Frankenberger and Andreas Pfützner
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0301 basic medicine ,Gynecology ,03 medical and health sciences ,medicine.medical_specialty ,030104 developmental biology ,0302 clinical medicine ,Coronavirus disease 2019 (COVID-19) ,business.industry ,030220 oncology & carcinogenesis ,Health Policy ,Medicine ,business - Abstract
ZusammenfassungDie Covid-19-Pandemie hat das deutsche Gesundheitssystem im Jahr 2020 vor erhebliche Herausforderungen gestellt. In diesem Zusammenhang ist es bemerkenswert, dass für die Zahnmedizin kein sogenannter Rettungsschirm aufgespannt wurde. Dies bedeutet, dass nach Ansicht der Bundesregierung Zahnärzte als nicht systemrelevant eingestuft wurden und somit offiziell auch nicht zu den Ärzten gehören. Diese Annahme ist grundfalsch und gefährlich, wie im Folgenden anhand eines wichtigen Beispiels erörtert wird.Das SARS-CoV-2-Virus führt bei infizierten Personen zu einem Beschwerdebild von leichten Erkältungszeichen bis hin zu lebensbedrohlichen beatmungsbedürftigen COVID-19-Pneumonien. Ein besonderes Risiko für schwere Verläufe haben Menschen höheren Alters sowie Patienten mit Diabetes, Bluthochdruck und anderen schweren Erkrankungen. Die Haupteintrittspforte für das SARS-CoV-2-Virus in den menschlichen Körper ist u. a. die orale Mukosa, denn die Viren reichern sich dort bevorzugt an und der ACE2-Rezeptor wird dort hochgradig exprimiert. Dieser Penetrationsweg erklärt die häufigeren schweren Verläufe bei älteren Diabetespatienten, deren Immunsystem bereits generell beeinträchtigt ist. Diabetes mellitus induziert eine chronische systemische Entzündung, die sich gerade im Mundbereich regelmäßig als Parodontitis manifestiert. Bei Diabetikern zwangsläufig oft auftretende Hyperglykämien schwächen die Mukosa-Barriere zusätzlich. Es ist daher dringend ratsam, bei Präventionsmaßnahmen für Diabetespatienten den Mund- und Rachenraum nicht zu ignorieren. Neben der parodontalprophylaktischen Betreuung ist gerade in Absenz von Zahnärzten die aktivierte Matrix-Metalloproteinase 8 (aMMP8) ein etablierter Biomarker. Die aktuellen Empfehlungen zur Prävention der SARS-CoV-2-assoziierten COVID-19-Erkrankung sollte daher um die Aspekte der Messung und Sanierung des Mund- und Rachenraums sowie einer regelmäßigen Desinfektion der oralen Mukosa erweitert werden.
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- 2020
4. Why Do People With Diabetes Have a High Risk for Severe COVID-19 Disease?—A Dental Hypothesis and Possible Prevention Strategy
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Michael Lazzara, Andreas Pfützner, and Julia Jantz
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Pediatrics ,viruses ,Endocrinology, Diabetes and Metabolism ,Gingiva ,Oral Health ,Disease ,Endocrinology ,0302 clinical medicine ,Risk Factors ,Pandemic ,Prevalence ,030212 general & internal medicine ,Age Factors ,virus diseases ,Middle Aged ,Breathing ,Angiotensin-Converting Enzyme 2 ,Coronavirus Infections ,Adult ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Pneumonia, Viral ,Biomedical Engineering ,030209 endocrinology & metabolism ,Bioengineering ,macromolecular substances ,Peptidyl-Dipeptidase A ,Letter to the Editors ,Diabetes Complications ,Betacoronavirus ,03 medical and health sciences ,Special Section: Personal Experiences With COVID-19 and Diabetes: An International Perspective ,Diabetes mellitus ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Periodontitis ,Saliva ,Pandemics ,Aged ,Mouth ,SARS-CoV-2 ,business.industry ,COVID-19 ,Models, Theoretical ,medicine.disease ,respiratory tract diseases ,Pneumonia ,nervous system ,Dentistry ,business ,Biomarkers - Abstract
The SARS-CoV-2 virus causes symptoms in infected individuals ranging from mild flu symptoms via severe COVID-19 pneumonia requiring ventilation to death. Risk factors for severe courses are age, di...
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- 2020
5. Laboratory Evaluation of Linearity, Repeatability, and Hematocrit Interference With an Internet-Enabled Blood Glucose Meter
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Andreas Pfützner, Valeria Kirsch, Mario Vogg, Filiz Demircik, Anke H. Pfützner, and Sanja Ramljak
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medicine.diagnostic_test ,business.industry ,Endocrinology, Diabetes and Metabolism ,Glucose meter ,Biomedical Engineering ,Linearity ,Bioengineering ,Repeatability ,Hematocrit ,Electronic diary ,Interference (communication) ,Internal Medicine ,Medicine ,business ,Glycemic ,Biomedical engineering - Abstract
Background: In recent clinical trials, use of the MyGlucoHealth blood glucose meter (BGM) and electronic diary was associated with an unusual reporting pattern of glycemic data and hypoglycemic events. Therefore, the performance of representative BGMs used by the patients was investigated to assess repeatability, linearity, and hematocrit interference in accordance with regulatory guidelines. Method: Ten devices and 6 strip lots were selected using standard randomization and repeatability procedures. Venous heparinized blood was drawn from healthy subjects, immediately aliquoted and adjusted to 5 target blood glucose (BG) ranges for the repeatability and 11 BG concentrations for the linearity tests. For the hematocrit interference test, each sample within 5 target BG ranges was split into 5 aliquots and adjusted to hematocrit levels across the acceptance range. YSI 2300 STAT Plus was used as the laboratory reference method in all experiments. Results: Measurement repeatability or precision was acceptable across the target BG ranges for all devices and strip lots with coefficient of variation (CV) between 3.4-9.7% (mean: 5.7%). Linearity was shown by a correlation coefficient of .991; however, a positive bias was seen for BG 100 mg/dL (ISO15197:2015 acceptance criteria: ±10%), while the results were acceptable for BG Conclusions: The BGM met repeatability requirements but demonstrated a significant measurement bias in the low BG range. In addition, it failed the ISO15197:2015 criteria for hematocrit interference.
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- 2019
6. 1077-P: De-escalation Treatment (DET): A Personalized Pharmacological Intervention to Stop Disease Progression in Patients with Type 2 Diabetes
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Andreas Pfützner, Linda Do, Anastasios Manessis, and Mina Hanna
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medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Hypoglycemia ,medicine.disease ,Metformin ,Insulin resistance ,Internal medicine ,Internal Medicine ,medicine ,business ,Pioglitazone ,De-escalation ,Progressive disease ,medicine.drug ,Glycemic - Abstract
Type 2 diabetes is a chronic progressive disease with increasing drug demands. It is comprised of a hereditary ß-cell dysfunction, (ßCD), insulin resistance (IR), and chronic systemic inflammation (CSI), which can be present with different degrees of severity. We have tested an alternative approach to the common drug escalation programs. DET (De-Escalation Treatment), temporary, multi-drug intervention targets to improve ß-Cell function and reverse disease progression. A personalized drug combination for a three-month treatment is determined based on a biomarker panel consisting of classic and new biomarkers. 22 patients (8 women, 14 men, age: 62±8 yrs., disease duration: 12±7 yrs., HbA1c: 7.8 %, BMI: 33.2±2.4 kg/m², treatment with 1 or 2 oral drugs) were treated with follow-up periods of up to 12 years. DET consisted of low doses each of basal insulin to address ßCD, treatment of IR (exercise and/or pioglitazone), a drug to reduce CSI (diet, GLP-1, or SGLTII) and a hypoglycemic intervention (metformin, or DPP-IV). The DET approach was well tolerated (nausea: 4 cases, edema: 1 case). All patients experienced a normalization or pronounced improvement of glycemic control without report of hypoglycemia. Mean HbA1c after 3 months was 5.9±0.4 %. Intact proinsulin decreased from 9.3±2.1 pmol/L to 2.3±0.6 pmol/L, adiponectin improved from 3.4±1.2 to 8.6±2.4 mg/dL, and mean body weight decreased by 2.4±1.1 kg (all: p11 years). Regeneration of ß-cell function by means of DET resulted in a temporary stop of chronic disease progression. A formal prospective clinical study to investigate the practicability of this approach in routine clinical practice is currently ongoing. Disclosure A. Pfützner: Consultant; Self; LifeCare, Inc., Novo Nordisk A/S. Research Support; Self; CNOGA Medical, Esperion Therapeutics, Inc. Speaker’s Bureau; Self; Sanofi-Aventis. A. Manessis: Research Support; Self; Novo Nordisk Inc., Sciema GmbH. L. Do: Research Support; Self; Sciema GmbH. M. Hanna: None. Funding Diabetes Treatment Centers International
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- 2020
7. Increased Intact Proinsulin in the Oral Glucose Challenge Sample is an Early Indicator for Future Type 2 Diabetes Development - Case Reports and Evidence from the Literature
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Jack Lewin, Anastasios Manessis, Andreas Pfützner, and Mina Hanna
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medicine.medical_specialty ,business.industry ,Type 2 diabetes ,medicine.disease ,Systemic inflammation ,General Biochemistry, Genetics and Molecular Biology ,Insulin resistance ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Medicine ,Biomarker (medicine) ,Prediabetes ,medicine.symptom ,business ,Proinsulin ,Morning - Abstract
Background Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic β-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of β-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for β-cell dysfunction and prediabetes. Methods A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours. Results All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes. Conclusions As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for β-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.
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- 2020
8. Evaluation of a New Noninvasive Glucose Monitoring Device by Means of Standardized Meal Experiments
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Filiz Demircik, Lisa Redert, Johannes Pfützner, Anke H. Pfützner, Andreas Pfützner, Stephanie Strobl, and Alexander Lier
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Adult ,Blood Glucose ,Male ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,030209 endocrinology & metabolism ,Bioengineering ,Diabetes treatment ,Eating ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Cog ,Internal Medicine ,Humans ,Medicine ,Statistical analysis ,030212 general & internal medicine ,Meals ,Aged ,Monitoring, Physiologic ,Meal ,business.industry ,Blood Glucose Self-Monitoring ,Healthy subjects ,Original Articles ,Middle Aged ,Reference Standards ,Postprandial Period ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Female ,Nuclear medicine ,business - Abstract
Background: Frequent blood glucose readings are the most cumbersome aspect of diabetes treatment for many patients. The noninvasive TensorTip Combo Glucometer (CoG) component employs dedicated mathematical algorithms to analyze the collected signal and to predict tissue glucose at the fingertip. This study presents the performance of the CoG (the invasive and the noninvasive components) during a standardized meal experiment. Methods: Each of the 36 participants (18 females and males each, age: 49 ± 18 years, 14 healthy subjects, 6 type 1 and 16 type 2 patients) received a device for conducting calibration at home. Thereafter, they ingested a standardized meal. Blood glucose was assessed from capillary blood samples by means of the (non)invasive device, YSI Stat 2300 plus, Contour Next at time points –30, 0, 15, 30, 45, 60, 75, 90, 120, 150, and 180 minutes. Statistical analysis was performed by consensus error grid (CEG) and calculation of mean absolute relative difference (MARD) in comparison to YSI. Results: For the noninvasive (NI) CoG technology, 100% of the data pairs were found in CEG zones A (96.6%) and B (3.4%); 100% were seen in zone A for the invasive component and Contour Next. MARD was calculated to be 4.2% for Contour Next, 9.2% for the invasive component, and 14.4% for the NI component. Conclusions: After appropriate individual calibration of the NI technology, both the NI and the invasive CoG components reliably tracked tissue and blood glucose values, respectively. This may enable patients with diabetes to monitor their glucose levels frequently, reliably, and most of all pain-free.
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- 2018
9. Serum-infrared spectroscopy is suitable for diagnosis of atherosclerosis and its clinical manifestations
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Dittmar Böckler, Andreas S. Peters, S. Demirel, Gunther Burgard, Maani Hakimi, Matthias Raster, Andreas Pfützner, and Jürgen Backhaus
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0301 basic medicine ,medicine.medical_specialty ,business.industry ,Carotid arteries ,Patient subgroups ,030204 cardiovascular system & hematology ,medicine.disease ,Gastroenterology ,Abdominal aortic aneurysm ,03 medical and health sciences ,Stenosis ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Aneurysm ,Internal medicine ,Healthy control ,Medicine ,business ,Spectroscopy ,Cause of death ,Artery - Abstract
Complications of atherosclerosis are the leading cause of death in Western civilization. In this pilot study we evaluated a new minimally invasive method for the diagnosis of atherosclerotic disorders by determining the typical fingerprint in the Fourier-transform infrared (FTIR) spectrum of 1 μL of a dried patient serum sample by neuronal network-assisted FTIR spectroscopy. In this study, samples from 54 healthy control subjects (Co, mean age 33, 32 males) were compared with samples from 141 atherosclerotic patients (AP, mean age 69, 103 males) suffering from peripheral occlusive artery disease (POAD: n = 47), carotid artery stenosis (CAS: n = 55), and abdominal aortic aneurysm (AAA: n = 39). By applying artificial neuronal network algorithms, the following sensitivities/specificities of the same spectra were determined: AP vs. Co: 99/98%, POAD vs. Co: 100/100%, CAS vs. Co: 93/98%, AAA vs. Co: 100/98%. No significant differentiation was possible between the three different patient subgroups. Based on the results of this exploratory pilot study, neuronal network-assisted FTIR might provide a promising, simple, cost-effective and minimally invasive method to diagnose the prevalence of atherosclerosis in affected patient populations prior to initiating more expensive imaging procedures.
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- 2017
10. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) in insulinomas: Indications and clinical relevance in a single investigator cohort of 47 patients
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Peter H. Kann, Maike Collienne, Simona R Bergmann, Detlef K. Bartsch, Andreas Pfützner, Gianluca Tamagno, Roland Moll, Verena Fourkiotis, Joachim N. Goebel, and Thomas Forst
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Adult ,Male ,Endoscopic ultrasound ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Biopsy ,medicine ,Humans ,Clinical significance ,Endoscopic Ultrasound-Guided Fine Needle Aspiration ,Pancreas ,Insulinoma ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Fine-needle aspiration ,Tolerability ,Female ,030211 gastroenterology & hepatology ,Radiology ,Complication ,business - Abstract
This study was aimed to investigate the role and relevance of endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of insulinomas. We have analysed the frequency, clinical indications, success rate (obtaining diagnostic tissue), diagnostic accuracy (in comparison to the pathological diagnosis after surgery), complications, and tolerability of endoscopic ultrasound-guided fine-needle aspiration biopsy and the localization and size of the lesions in 47 consecutive patients (29 females, 18 males; 46 ± 15 years) who had surgery for insulinoma following fasting test and were explored by single investigator EUS 1994–2015. Endoscopic ultrasound-guided fine-needle aspiration biopsy was performed in 21 % (10/47) of the patients. The clinical indications for endoscopic ultrasound-guided fine-needle aspiration biopsy were non-conclusive result of fasting test (n = 7), missing toxicology (n = 2), suspected malignancy at EUS (n = 1), suspicious extra-pancreatic localization of the lesion (n = 1). The diagnostic success rate of the procedure was 80 % (8/10 cases), the diagnostic accuracy of the fine-needle aspiration biopsy 70 % (7/10 cases). The lesions undergoing endoscopic ultrasound-guided fine-needle aspiration biopsy were localized in the cauda (n = 5), corpus (n = 2), caput/processus uncinatus (n = 3), the diameter of the tumors was 21 ± 18 (10–70) mm. Only one accidental vascular puncture without any clinical complication occurred and all patients tolerated the procedure well. In the majority of cases, positive fasting test, negative toxicology, and detection of a typical pancreatic lesion at endoscopic ultrasound is sufficient for the diagnosis of insulinoma and the definition of the appropriate surgical strategy. Based on our data, we suggest including endoscopic ultrasound-guided fine-needle aspiration biopsy in the diagnostic work-up of organic hyperinsulinism in selected patients with inconclusive or uncertain diagnosis before surgery.
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- 2016
11. Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
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Ruilope, Luis M, Agarwal, Rajiv, Anker, Stefan D, Bakris, George L, Filippatos, Gerasimos, Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Mentenich, Nicole, Pitt, Bertram, Diego, Besada, Alfredo, Wassermann, Julio, Bittar, Alicia, Elbert, Augusto, Vallejos, Gloria, Viñes, Hugo, Sanabria, Federico Pérez Manghi, Alberto, Liberman, Inés, Bartolacci, Diego, Aizenberg, Mariano, Chahin, Laura, Maffei, Elizabeth, Gelersztein, Bernhard, Ludvik, Hans-Robert, Schönherr, Heinz, Drexel, Wolfgang, Preiß, Ursula, Hanusch, Peter, Neudorfer, Friedrich, Prischl, Bernhard, Paulweber, Christoph, Ebenbichler, Rudolf, Prager, Harald, Sourij, Gerit-Holger, Schernthaner, Martin, Clodi, Evelyn, Fliesser-Görzer, Elif, Ekinci, Richard, Macisaac, David, Packham, Hugo, Stephenson, Michael, Suranyi, Gary, Wittert, Katie-Jane, Wynne, Alexia, Pape, Duncan, Topliss, Peter, Colman, Craig, Nelson, James, Vandeleur, David, Colquhoun, Simon, Roger, Peak Mann Mah, Walter, Abhayaratna, Luc VAN Gaal, Pieter, Gillard, Jean-Michel, Hougardy, Marijn, Speeckaert, Koen, Stas, Wendy, Engelen, Francis, Duyck, André, Scheen, Hilde, Vanbelleghem, Peter, Doubel, Svetla, Vasileva, Rosen, Rashkov, Boyan, Nonchev, Theodora, Temelkova-Kurktschieva, Mariana, Yoncheva-Mihaylova, Rangel, Rangelov, Neli, Klyuchkova, Pavel, Stanchev, Zhivko, Tagarev, Radostina, Boshnyashka, Petya, Manova, Zhulieta, Prakova, Mariya, Lucheva, Valentina, Gushterova, Ghassan, Farah, Dimitar, Georgiev, Mariyana, Pichmanova, Dotska, Minkova, Bilyana, Stoyanovska-Elencheva, Maria Eugenia Canziani, Miguel, Hissa, Irene, Noronha, Joao Eduardo Salles, Daniela, Antunes, Freddy, Eliaschewitz, Carlos Eduardo Figueiredo, Rogerio de Paula, Luis, Canani, Maurilo Leite Jr, Bruno, Paolino, Rosangela, Rea, Sergio, Vencio, Claudia, Brito, Raphael, Paschoalin, Roberto Pecoits Filho, Eduardo, Vasconcellos, Nathalia, Paschoalin, Adriana, Forti, Roberto, Botelho, Miguel, Riella, Dalton, Precoma, Maria, Cerqueira, Lilia, Maia, Evandro, Portes, Marcio, Pereira, Joanne, Liutkus, Dennis, O Keefe, Richard, Tytus, Brian, Carlson, James, Conway, Michael, Walsh, Igor, Wilderman, Andrew, Steele, Sheldon, Tobe, Louise, Vitou, Karthik, Tennankore, Valdemar, Martinho, Philip, Mcfarlane, Daniel, Shu, Serge, Cournoyer, Richard, Dumas, Giuseppe, Mazza, Guy, Tellier, George, Tsoukas, Stanley, Weisnagel, Jean-Francois, Yale, Sameh, Fikry, Randolph, Hart, Pavel, Hamet, Francois, Madore, Paul, Barre, Daniel, Schwartz, Allan, Kelly, Ivor, Teitelbaum, Sean, Peterson, Sam, Henein, Richard, Goluch, Gregoire, Wuerzner, Markus, Laimer, Stefan, Bilz, Marc, Donath, Gottfried, Rudofsky, Christopher, Strey, Antoinette, Pechère-Bertschi, Paola, Varleta, Fernando, González, Marcelo, Medina, Carmen, Romero, Victor, Saavedra, Juan Carlos Prieto, Eliana, Reyes, Juan Carlos Palma, Jorge, Cobos, Zhihong, Liu, Dalong, Zhu, Nan, Chen, Fang, Liu, Wang, Li, Qing, Su, Bingyin, Shi, Aiping, Yin, Hao, Wang, Yan, Li, Jianying, Niu, Chaoqing, Wu, Xinjun, Wang, Ying, Zhang, Peng, Ai, Jianhua, Ma, Yuxiu, Li, Hongguang, Zheng, Minxiang, Lei, Zhaohui, Mo, Nanwei, Tong, Jinluo, Cheng, Youping, Dong, Xudong, Xu, Qinkai, Chen, Tianjun, Guan, Gang, Long, Changying, Xing, Ling, Li, Yinghong, Liu, Hao, Zhang, Ling, Zhong, Zhonghe, Li, Longyi, Zeng, Jiali, Wei, Hanqing, Cai, Tianfeng, Wu, Weiping, Lu, Ning, Xu, Yibing, Lu, Dejun, Chen, Ruifang, Bu, Jiansong, Shen, Junwu, Dong, Zhiquan, Zhao, Fei, Xiong, Fangfang, Jiang, Jinkui, Yang, Jian, Kuang, Guoyuan, Lu, Lihua, Wang, Yanlin, Zhang, Shuifu, Tang, Weiying, Guo, Jian, Liu, Sheng, Jiang, Fang, Yi, Yuming, Du, Zhuxing, Sun, Yuantao, Liu, Liyong, Zhong, Dongmei, Li, Hongmei, Li, Chuanming, Hao, Feixia, Shen, Jianqin, Wang, Jingmei, Li, Dora, Molina, Carlos, Cure, Jaime, Ibarra, Gustavo, Aroca, Hernán, Yupanqui, Eric, Hernández, Mónica, López, Gregorio, Sánchez, Germán, Barreto, Edgar, Arcos, Miguel, Urina, William, Kattah, Carlos, Durán, Clara, Arango, Julian, Coronel, Guillermo, Blanco, Mónica, Terront, Gustavo, Guzmán, Luis, García, Carlos, Jaramillo, Manuel, Liévano, Diego, Benitez, Tatiana, Cárdenas, Iván, Villegas, Sandra, Barrera, Nicolás, Jaramillo, Rodrigo, Botero, Nelly Beltrán López, Freddy, Trujillo, Martin, Prazny, Jitka Hasalova Zapletalova, Libor, Okenka, Dino, Alferi, Tomas, Edelsberger, Pavel, Tomanek, Jiri, Brezina, Olga, Hola, Jana, Houdova, Petr, Bucek, David, Karasek, Sarka, Kopecka, Richard, Kovar, Michal, Brada, Lucie, Hornova, Eva, Krcova, Hana, Lubanda, Vlasta, Kutejova, Jiri, Kuchar, Helena, Hrmova, Jiri, Pumprla, Magdalena, Mokrejsova, Drahomira, Gulakova, Ivo, Matyasek, Thilo, Krüger, Hermann, Haller, Thorsten, Koch, Ludger, Rose, Diethelm, Tschöpe, Lutz, Stemler, Volker, Schettler, Andreas, Pfützner, Karl, Derwahl, Thomas, Horacek, Helena, Sigal, Heidrun, Täschner, Ingolf, Schiefke, Andreas, Hagenow, Andreas, Birkenfeld, Christoph, Axthelm, Christoph, Wanner, Klaus, Busch, Heike, Schlichthaar, Christoph, Hasslacher, Stefan, Degenhardt, Markus van der Giet, Georg, Strack, Norbert, Schöll, Bernhard, R Winkelmann, Lars, Rump, Ruth, Nischik, Bernd, Schröppel, Thomas, Giebel, Achim, Ulmer, Andrea, Rinke, Christel, Contzen, Wolfgang, Jungmair, Nicole, Toursarkissian, Christof, Kloos, Joachim, Müller, Thomas, Schürholz, Hermann, Braun, Frank, Pistrosch, Per, Poulsen, Claus, Juhl, Joan, Nielsen, Jesper, Bech, Ole, Rasmussen, Peter, Rossing, Jens, Faber, Thure, Krarup, Morten, Lindhardt, Ulrik Pedersen-Bjergaard Pedersen-Bjergaard, Karoline, Schousboe, Jørgen, Hangaard, Sten, Madsbad, Gunnar, Gislason, Grzegorz Jaroslaw Pacyk, Olga González Albarrán, Carlos Sánchez Juan, José Julián Segura de la Morena, Secundino Cigarrán Guldris, Francisco Martínez Deben, José María Pascual Izuel, Julio Pascual Santos, Francesca, Calero, Alfonso, Soto, Manuel Polaina Rusillo, Josep, Redón, Josep, Galcerán, Juan, Mediavilla, Mª Dolores Martínez Esteban, Alfredo, Michán, Fernando de Álvaro, Javier Escalada San Martín, Josep Cruzado Garrit, Cristina, Castro, Fernando Cereto Castro, Rafael Santamaría Olmo, Esteban, Poch, Judith, Martins, Julio Hernández Jaras, Meritxell, Ibernón, Daniel, Seron, Hanane, Bouarich, Maribel, Troya, Jorma, Strand, Ilkka, Kantola, Sakari, Nieminen, Arvo, Koistinen, Kristiina, Kananen, Sakari, Sulosaari, Mikko, Honkasalo, Pirkko, Korsoff, Tuomo, Nieminen, Karita, Sadeharju, Kari, Humaloja, Jorma, Lahtela, Philippe, Zaoui, Jean-Pierre, Fauvel, Ronan, Roussel, Didier, Gouet, Pierre, Serusclat, Sylvaine, Clavel, Bruno, Guerci, Bruno, Verges, Olivier, Moranne, Arnaud, Monier, Alexandre, Klein, François, Chantrel, Yannick LE Meur, Rafik, Mesbah, Bertrand, Cariou, Dominique, Guerrot, Karim, Gallouj, Kieran, Mccafferty, Arutchelvam, Vijayaraman, Yuk-Ki, Wong, Dhanya, Kalathil, Sam, Rice, Sui Phi Kon, Hassan, Kahal, Cuong, Dang, Fahmy, Hanna, Christina, Kyriakidou, Imrozia, Arif, Anne, Kilvert, Pauline, Swift, Ioannis, Stefanidis, Ploumis, Passadakis, Aikaterini, Papagianni, Erifili, Hatziagelaki, Dorothea, Papadopoulou, Ioannis, Boletis, Ioanna, Makriniotou, Theodora, Kounadi, Ioannis, Ioannidis, Paul, Lee, Ching Wan Ronald Ma, Vincent, Yeung, Tai Pang Ip, Ebrahim, Noori, Julianna, Kiss, Eleonora, Harcsa, Albert, Szocs, Szilard, Vasas, Krisztina, Wudi, Robert, Kirschner, Dora, Bajcsi, Beata, Lamboy, Botond, Literati-Nagy, Gabor, Nyirati, Gizella, Petro, Karoly, Schneider, Katalin, Keltai, Akos, Kalina, Peter, Danos, Szilvia, Kazup, Zsolt, Zilahi, Judit, Simon, Laszlo, Kovacs, Marianna, Zsom, Margit, Mileder, Laszlo, Nagy, Yoram, Yagil, Julio, Wainstein, Ofri, Mosenzon, Rosane Abramof Ness, Sydney Ben Chetrit, Faiad, Adawi, Idit, Liberty, Ehud, Grossman, Mazen, Elias, Zaher, Armaly, Evgeny, Farber, Assy, Nimer, Amir, Bashkin, Gil, Chernin, Shai, Efrati, Doron, Schwartz, Noa Berar Yanay, Mariela, Glandt, Robert, Zukermann, Majdi, Halabi, Shaul, Atar, Mahmud, Darawsha, Norberto, Perico, Gaetano La Manna, Giovanni Giorgio Battaglia, Domenico, Santoro, Piermarco, Piatti, Bonora, Enzo, Davide Carlo Maggi, Paolo, Calabrò, Roberto, Cimino, Roberto, Trevisan, Paolo, Fiorina, Antonio, Pisani, Antonello, Pani, Gennaro, Santorelli, Carlo Antonio Bossi, Giancarlo, Tonolo, Enrico, Fiaccadori, Anna Maria Veronelli, Michele, Emdin, Paola, Ponzani, Maria Cristina Gregorini, Franco Luigi Cavalot, Carlo Bruno Giorda, Taro, Shibasaki, Akihiro, Hamasaki, Takashi, Nomiyama, Sunao, Matsubayashi, Junji, Shinoda, Kazunari, Matsumoto, Hideo, Kanehara, Yoshihide, Hirohata, Masayo, Yamada, Jun, Nakazawa, Yoshimitsu, Yamasaki, Mikihiro, Nakayama, Ryuichi, Furuya, Osamu, Ebisui, Satsuki, Kawasaki, Daishiro, Yamada, Masayuki, Noritake, Tamayo, Ishiko, Nobuhiro, Sasaki, Daisuke, Suzuki, Asami, Tanaka, Miyuki, Kubota, Hideo, Araki, Hiroshi, Ohashi, Takeshi, Osonoi, Kazuo, Yamagata, Naruhiro, Fujita, Daisuke, Kanda, Seiichi, Tanaka, Junko, Koide, Masao, Ishii, Takayuki, Ogiwara, Masaaki, Suzuki, Taiji, Sekigami, Takayuki, Higashi, Yuko, Yambe, Yoshiro, Kusano, Hidetoshi, Kikuchi, Hiroaki, Miyaoka, Kiyoe, Kato, Masayuki, Kashima, Fumiko, Yamakawa, Shuji, Horinouchi, Hirofumi, Imoto, Hiroshi, Sobajima, Hidetoshi, Kanai, Naoki, Matsuoka, Hirotaka, Shibata, Akemi, Inagaki, Toshiyuki, Sugiura, Toru, Sugiyama, Hidekatsu, Yanai, Yoshiyuki, Hamamoto, Masahiro, Hatazaki, Terumasa, Hayashi, Kunihisa, Kobayashi, Satoshi, Murao, Makoto, Ujihara, Kazuya, Sugitatsu, Katsunori, Kawamitsu, Ken, Yamakawa, Izumi, Tsunematsu, Fumi, Kikuchi, Hideaki, Jinnouchi, Tetsuyuki, Yasuda, Hajime, Maeda, Yasuto, Matsuo, Hideki, Okamoto, Takeshi, Katsuki, Ken, Yajima, Takeshi, Morita, Masayuki, Inagaki, Wooje, Lee, Jungoo, Kang, Cheol Young Park, Hyesoon, Kim, Singon, Kim, Youcheol, Hwang, Injoo, Kim, Jaehyeon, Kim, Young Min Cho, Byungwan, Lee, Choonhee, Chung, Soo, Lim, Jae Myung Yu, Dovile, Kriauciuniene, Antanas, Navickas, Audrone, Velaviciene, Egle, Urbanaviciene, Gediminas, Urbonas, Jurate, Lasiene, Lina, Radzeviciene, Ron, Gansevoort, Adriaan, Kooy, G Lieverse, A, L Penne, E, Ruud J, M van Leendert, M van Buren, H Boonstra, A, C Bakker, R, Marielle, Krekels, B Brouwer, C, T Luik, P, J N, M Barendregt, Bert-Jan van den Born, Trine, Finnes, Thomas, Karlsson, Hilde, Selsås, Emil, Asprusten, Robert, Hagemeier, Erik, Eriksen, Knut, Risberg, Hans, Høivik, Leidulv, Solnør, Frode, Thorup, Jan, Rocke, Rick, Cutfield, Peter, Dunn, Jeremy, Krebs, Russell, Scott, Kingsley, Nirmalaraj, Nine, Smuts, John, Baker, Veronica, Crawford, Albert, Bautista, Roberto, Mirasol, Elizabeth, Catindig, Glenda, Pamugas, Louie, Tirador, Maribel, Tanque, Janusz, Gumprecht, Piotr, Napora, Edward, Franek, Andrzej, Stankiewicz, Katarzyna, Landa, Agnieszka, Tiuryn-Petrulewicz, Kazimierz, Ciechanowski, Bogna, Wierusz-Wysocka, Barbara, Rewerska, Grazyna, Cieslik, Michal, Hoffmann, Michal, Nowicki, Jolanta, Krzykowska, Stanislaw, Mazur, Katarzyna, Wasilewska, Anna, Ocicka-Kozakiewicz, Ewa, Skokowska, Renata, Wnetrzak-Michalska, Jan, Ruxer, Patrycja, Butrymowicz, Katarzyna, Madziarska, Ilona, Kurnatowska, Teresa, Rusicka, Adam, Madrzejewski, Tomasz, Stompor, Jose, Guia, Amalia, Pereira, Pedro, Melo, Cristina, Roque, Francisco, Rosario, Fernando Teixeira, E Costa, Fernando, Nolasco, Edgar, Almeida, Pedro, Matos, Cesar, Esteves, Rui, Carvalho, Ilidio, Brandao, Susana, Heitor, Ana Vila Lobos, Rosa, Ballesteros, Gil, Silva, Carlos, Barreto, Ana, Silva, Natalya, Vorokhobina, Alexander, Sherenkov, Ivan, Gordeev, Olga, Semenova, Sergey, Levashov, Vyacheslav, Marasaev, Ruslan, Sardinov, Vadim, Klimontov, Vitaliy, Baranov, Nadezhda, Verlan, Albert, Galyavich, Arkadiy, Demko, Zhanna, Kobalava, Elena, Zakharova, Lyudmila, Kvitkova, Oleg, Solovev, Elena, Smolyarchuk, Larisa, Zhukova, Elena, Zhdanova, Andrey, Babkin, Galina, Nechaeva, Olga, Barbarash, Elena, Rechkova, Roman, Libis, Elena, Kosmacheva, Tatyana, Rodionova, Irina, Ipatko, Alexander, Dreval, Nina, Petunina, Elena, Chernyavskaya, Alsu, Zalevskaya, Yuriy, Khalimov, Tatyana, Zykova, Anton, Edin, Ashot, Mkrtumyan, Shamil, Palyutin, Vyacheslav, Mareev, Leonid, Strongin, Olga, Ukhanova, Mikhail, Antsiferov, Davyd, Yakhontov, Leonid, Pimenov, Natalya, Koziolova, Konstantin, Nikolaev, Imad, Merai, Olga, Zanozina, Leyla, Gaysina, Mikhail, Arkhipov, Natalia, Malykh, Oksana, Rymar, Vladimir, Martynenko, Sofya, Malyutina, Polina, Ermakova, Marina, Kalashnikova, Bengt-Olov, Tengmark, Carl-Johan, Lindholm, Dan, Curiac, Ken, Eliasson, Erik, Rein-Hedin, Gregor, Guron, Inga, Soveri, Annette, Bruchfeld, Jonas, Spaak, Malin, Frank, Magnus, Löndahl, Hans, Larnefeldt, Margareta, Hellgren, Olof, Hellberg, Yong Mong Bee, Chee Fang Sum, Ru San Tan, Piyamitr, Sritara, Chaicharn, Deerochanawong, Chatlert, Pongchaiyakul, Natapong, Kosachunhanan, Bancha, Satirapoj, Ahmet, Temizhan, Ibrahim, Gul, Ramazan, Sari, Aytekin, Oguz, Mustafa, Tigen, Huseyin, Yilmaz, Ozer, Badak, Oner, Ozdogan, Talat, Tavli, Necmi, Eren, Murat, Cayli, Sedat, Ustundag, Yavuz, Yenicerioglu, Ismail, Kocyigit, Abdulbaki, Kumbasar, Idris, Sahin, Lee-Ming, Chuang, Ju-Ying, Jiang, Chien-Te, Lee, Der-Cherng, Tarng, Shih-Te, Tu, Mai-Szu, Wu, Ming-Ju, Wu, Chiz-Tzung, Chang, Cheng-Chieh, Hung, Liubov, Sokolova, Borys, Mankovsky, Dmytro, Kogut, Viktoriia, Chernikova, Kateryna, Malyar, Nonna, Kravchun, Volodymyr, Botsyurko, Vitaliy, Maslyanko, Liliya, Martynyuk, Oleksandr, Serhiyenko, Vasyl, Stryzhak, Halyna, Myshanych, Oleksandra, Donets, Iryna, Bondarets, Maryna, Vlasenko, Nataliia, Pertseva, Mariia, Grachova, Ivan, Smirnov, Larysa, Pererva, Ivan, Fushtey, Julia, Komisarenko, Anna, Isayeva, Carl, Meisner, Bobby, Khan, Louis, Maletz, Bradley, Dixon, Ahmed, Arif, Timothy, Jackson, Mirela, Ponduchi, Mahfouz El Shahawy, Salil, Nadkarni, Daniel, Urbach, Jorge, Paoli-Bruno, Henry, Lora, Umar, Farooq, Steven, Zeig, Lance, Rudolph, Nabil, Andrawis, William, Kaye, Jill, Meyer, Khalid, Bashir, Glenn, Heigerick, James, Smelser, Javier Ricardo Colomar, David, Scott, Brian, First, Stuart, Handelsman, Jose, Bautista, Rajesh, Patel, Stephen, Minton, Juan, Frias, Luis, Ramos-Gonez, John, Bertsch, Ali, Iranmanesh, Vivian, Fonseca, Michael, Yuryev, Larry, Popeil, Jose, Cardona, Sanjeev, Saxena, Santosh, Sharma, Edgar, Gonzalez, Richard, Solomon, Muhammad, Khan, Ahmed, Awad, David, Fitz-Patrick, Douglas, Linfert, David, Grant, Susan, Brian, Leon, Fogelfeld, Rafael, Canadas, Pablo, Pergola, Joseph, Soufer, Rakesh, Patel, Shujauddin, Valika, Jonathan, Winston, Allison, D, Maria, Caramori, Stanley, Koch, Anjay, Rastogi, Jonathan, Bornfreund, Michael, Rocco, Maxine, Hamilton, Luis, Garcia-Mayol, Peter, Weissman, Suzanne, Oparil, Gary, Ruoff, Kyaw, Soe, Gary, Korff, Robert, Busch, Alexander, Lurie, Israel, Hartman, Garfield, Samuels, Derek, Lejeune, Visal, Numrungroad, Stephen, Brietzke, Zeid, Kayali, Harold, Szerlip, Steven, Barag, Gilberto, Seco, Damaris, Vega, Osvaldo, Brusco, Camil, Kreit, Humberto, Cruz, Bharat, Mocherla, Sharma, Prabhakar, George, Fadda, Martin, Valdes, Eugene, Soroka, Ramin, Berenji, Sreedhara, Alla, Shweta, Bansal, Odugbesan, A, Karlton, Pettis, Masoud, Azizad, Idalia, Acosta, Atoya, Adams, William, Sanchez, Rosa, Suarez, Efrain, Reisin, Carlos, Herrera, Keung, Lee, Csaba, Kovesdy, Adam, Whaley-Connell, Aldo, Peixoto, Ronald, Mayfield, Mahendra, Jain, Earl, Martin, Paul, Norwood, Jonathan, Wise, Hugo, Romeu, Stephen, Halpern, Mustafa, Mandviwala, Thomas, Turk, Anna, Burgner, David, Bleich, Ankur, Doshi, Jose, Carpio, Jorge, Posada, Alexander, Magno, Samer, Nakhle, Gary, Goldstein, Caroline, Mbogua, Dierdre, Mcmullen, Dilawar, Ajani, Wayne, Kotzker, Nelson, Kopyt, Richard, Treger, Yusuf, Ruhullah, Sharon, Adler, Harjeet, Brar, Marc, Rendell, Dennis, Ross, Srinivasan, Beddhu, German, Hernandez, Sylvia, Rosas, M Sue Kirkman, Mohammed, El-Shahawy, Jeffrey, Rothman, Ahmad, Barakzoy, Aparna, Tamirisa, Sabrina, Benjamin, Michael, Bahrami, Prabir, Roy-Chaudhury, Ramprasad, Dandillaya, Gretel, Trullenque, Jose, Birriel, John, Flack, Karen, Johnson, Brenda, Lemus, Guillermo, Umpierrez, Geetha, Maddukuri, Kenneth, Jamerson, Christopher, Case, Patrick, Fluck, Saeed, Kronfli, Violet, Habwe, Bala, Subramanian, Tariq, Shafi, Rupesh, Raina, Roland, Fernando, Sourabh, Kharait, Carlos, Hernandez-Cassis, Raymond, Fink, Jamal, Hammoud, Amer, Al-Karadsheh, Manuel, Montero, Philip, Nicol, Jesus, Navarro, Michael, Shanik, Zia, Din, Francisco, Gonzalez-Abreu, Sam, Lerman, Claude, Galphin, John, Evans, Ashwini, Gore, Radica, Alicic, Mandeep, Sahani, Roberto, Pisoni, Tuan-Huy, Tran, Jeffrey, Ryu, Harvey, Serota, Nilda, Neyra, Richard, O Donovan, Sreedhar, Mandayam, Moustafa, Moustafa, Mark, Smith, Arvind, Krishna, Arjun, Sinha, Anuj, Bhargava, Kodangudi, Ramanathan, Soni, Dhanireddy, Stephen, Thomson, Romanita, Nica, Emaad, Abdel-Rahman, Mark, Barney, Mariana, Markell, Nauman, Shahid, David, Oliver, Tran, Khanh, Pham Nguyen Son, Lam VAN Hoang, Boi Ngoc Nguyen, Nguyen Minh Nui, Lan Phuong Tran, Fayzal, Ahmed, Dorothea, Urbach, Dirkie Jansen van Rensburg, Gracjan, Podgorski, Aslam, Amod, Sindeep, Bhana, Shaifali, Joshi, Essack, Mitha, Deepak, Lakha, Louis van Zyl, Trokis, J, Naresh, Ranjith, Mary, Seeber, Mohamed, Sarvan, Mohammed, Tayob, Brian, Rayner, Larry, Distiller, Heidi, Siebert, Mukesh, Joshi, Paul, Rheeder, Magdalena Madero Rovalo, Gustavo Solache Ortiz, Gustavo Méndez Machado, Rafael Valdez Ortiz, Juan Villagordoa Mesa, Saúl Irizar Santana, Sandro Avila Pardo, Jorge Escobedo de la Peña, Guillermo González Gálvez, Leobardo Sauque Reyna, Miriam Bastidas Adrian, Guillermo Fanghänel Salmón, Ramiro Gutiérrez Ochoa, Luis Nevarez Ruiz, Gabriel Ramos López, Alfredo Chew Wong, Arturo Saldaña Mendoza, Pedro García Hernández, José González González, Melchor Alpizar Salazar, José Lazcano Soto, Amaury, Roman-Miranda, Gregorio, Cortes-Maisonet, Liana, Turcu, Adriana, Dumitrescu, Gabriela, Radulian, Hortensia, Barbonta, Cristina, Mistodie, Georgeta, Vacaru, Alexandrina, Popescu, Adrian, Vlad, Silvia, Paveliu, Nicoleta, Mindrescu, Adrian, Albota, Ella, Pintilei, Lavinia, Pop, Gabriela, Negrisanu, Doina, Catrinoiu, Cornelia, Bala, Amorin, Popa, Iosif, Szilagyi, Ciprian, Constantin, Elena, Caceaune, Adriana, Onaca, Li Yuan Lee, Nor Azizah Aziz, Wan Mohd Izani Wan Mohamed, Wan Hasnul Halimi Bin Wan Hasan, Jeyakantha, Ratnasingam, Nik Nur Fatnoon Nik Ahmad, Rizmy Najme Khir, Norhaliza Mohd Ali, Masni, Mohamad, Chek Loong Loh, Joe, Eustace, John, Holian, Donal, Reddan, Yvonne, O Meara, Mensud, Hatunic, Zuzana, Ochodnicka, Dalibor, Sosovec, Andrej, Dzupina, Ingrid, Buganova, Jana, Babikova, Denisa, Spodniakova, Ruilope, L, Agarwal, R, Anker, S, Bakris, G, Filippatos, G, Nowack, C, Kolkhof, P, Joseph, A, Mentenich, N, Pitt, B, Trevisan, R, Pathology/molecular and cellular medicine, Diabetes Pathology & Therapy, and Diabetes Clinic
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Male ,Endocrinology, Diabetes and Metabolism ,Enfermedad cardiovascular ,030232 urology & nephrology ,BAY 94-8862 ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Diabete ,Kidney ,Aparato circulatorio ,Azúcar ,chemistry.chemical_compound ,Mineralocorticoid Receptor Antagonists/therapeutic use ,0302 clinical medicine ,Medicine and Health Sciences ,Diabetic Nephropathies ,Myocardial infarction ,Renal Insufficiency ,Chronic ,Aldosterone ,Outcome ,Mineralocorticoid Receptor Antagonists ,RISK ,COMPLICATIONS ,Diabetes ,Middle Aged ,SPIRONOLACTONE ,CHRONIC HEART-FAILURE ,Treatment Outcome ,Mineralocorticoid ,Nephrology ,Cardiovascular Diseases ,Research Design ,Disease Progression ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Type 2 ,Glomerular Filtration Rate ,medicine.medical_specialty ,Finerenone ,Naphthyridines/therapeutic use ,Renal function ,Outcomes ,03 medical and health sciences ,Clinical ,Double-Blind Method ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Naphthyridines ,Renal Insufficiency, Chronic ,ANTAGONIST ,Sistema cardiovascular ,Aged ,Patient-Oriented, Translational Research: Research Article ,Diabetic Nephropathies/complications ,Renal Insufficiency, Chronic/drug therapy ,RECEPTOR ,Aldosterone, Clinical, Diabetes, Kidney, Mineralocorticoid, Outcomes ,business.industry ,Cardiovascular Diseases/epidemiology ,Diabetes Mellitus, Type 2/complications ,MILD ,WORSENING RENAL-FUNCTION ,EFFICACY ,medicine.disease ,chemistry ,Diabetes Mellitus, Type 2 ,Spironolactone ,Albuminuria ,business ,Kidney disease ,Follow-Up Studies - Abstract
Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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- 2019
12. System Accuracy Assessment of a Combined Invasive and Noninvasive Glucometer
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Johannes Pfützner, Filiz Demircik, Stephanie Strobl, Kim Kessler, Alexander Lier, Jan Spatz, Andreas Pfützner, and Anke H. Pfützner
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Diabetes treatment ,System a ,Predictive Value of Tests ,Internal Medicine ,medicine ,Humans ,Intensive care medicine ,Aged ,Reagent Strips ,business.industry ,Blood Glucose Self-Monitoring ,Reproducibility of Results ,Original Articles ,Equipment Design ,Middle Aged ,Cross-Sectional Studies ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Female ,business ,Biomarkers - Abstract
Background: The pain associated with pricking the fingertip for blood glucose self-testing is considered to be a major burden in diabetes treatment. This study was performed to evaluate the system accuracy of the invasive TensorTip Combo Glucometer (CoG) device component in accordance with ISO15197:2015 requirements and to explore the accuracy of the noninvasive tissue glucose prediction component. Methods: One hundred samples were obtained from people with type 1 and type 2 diabetes and healthy volunteers (43 females, 57 males; age: 53 ± 16 years), with glucose distribution as requested by the ISO standard. Three strip lots were tested twice by healthcare professionals in comparison to YSI 2300 Stat Plus reference method followed by a noninvasive tissue glucose reading (NI-CoG). Mean Absolute (Relative) Difference (MARD) was calculated and a consensus error grid (CEG) analysis was performed. Results: The ISO system accuracy criteria were met with the invasive strip technology by 586/600 of the data points (97.1%) and for each strip lot separately. All invasive results (100%) were within CEG-zone A and total MARD was calculated to be 7.1%. With the noninvasive reading, 99% of raw data points were in A + B (91.1% and 7.8%), and the total MARD was calculated to be 18.1%. Discussion: The invasive component of the CoG device was shown to be in full compliance with the current ISO15197 criteria. Good results were also obtained with the NI-CoG tissue glucose prediction. This noninvasive technology would potentially be suitable for frequent pain-free glucose monitoring in many people with diabetes.
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- 2019
13. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial
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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
14. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
- Author
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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
15. System Accuracy Assessment of a Blood Glucose Meter With Wireless Internet Access Associated With Unusual Hypoglycemia Patterns in Clinical Trials
- Author
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Jan Spatz, Andreas Pfützner, Mina Hanna, Johannes Pfützner, Stephanie Strobl, Filiz Demircik, Anke H. Pfützner, and Valeria Kirsch
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Hypoglycemia ,Sensitivity and Specificity ,law.invention ,Endocrinology ,Randomized controlled trial ,law ,Internal Medicine ,Diabetes Mellitus ,Medicine ,Humans ,Wireless internet access ,Glycemic ,Randomized Controlled Trials as Topic ,Clinical Trials as Topic ,Data collection ,business.industry ,Glucose meter ,Blood Glucose Self-Monitoring ,Data Collection ,Reproducibility of Results ,Repeatability ,Equipment Design ,Original Articles ,Middle Aged ,medicine.disease ,Clinical trial ,Equipment Failure Analysis ,Emergency medicine ,Practice Guidelines as Topic ,Female ,business ,Wireless Technology ,Internet Access - Abstract
Background: In recent randomized clinical trials, an unusual reporting pattern of glycemic data and hypoglycemic events potentially related to an internet enabled blood glucose meter (MyGlucoHealth, BGM) was observed. Therefore, this clinical study was conducted to evaluate the system accuracy of the BGM in accordance with the ISO15197:2015 guidelines with additional data collection. Methods: To investigate system accuracy, 10 of 3088 devices and 6 of 23 strip lots, used in the trials, were selected by a randomization procedure and a standard repeatability assessment. YSI 2300 STAT Plus was used as the standard reference method. The samples were distributed as per the ISO15197:2015 recommendations with 20 additional samples in the hypoglycemic range. Each sample was tested with 6 devices and 6 strip lots with double determinations. Results: Overall, 121 subjects with blood glucose values 26-423 mg/dL were analyzed, resulting in 1452 data points. In all, 186/1452 readings (12.8%) did not meet the ISO acceptance criteria. Data evaluated according to the FDA guidelines showed that 336/1452 (23.1%) readings did not meet the acceptance criteria. A clear bias toward elevated values was observed for BG Conclusions: The results show that the BGM, although approved according to standard regulatory guidelines, did not meet the level of analytical accuracy required for clinical treatment decisions according to ISO 15197:2015 and FDA requirements. In general, caution should be exercised before selection of BGMs for patients and in clinical trials.
- Published
- 2019
16. Clinical and Laboratory Evaluation of a New Specific Point-of-Care Test for Intact Proinsulin
- Author
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Gunther Burgard, Andreas Pfützner, Peter H. Kann, and Anke H. Pfützner
- Subjects
Adult ,Male ,Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Point-of-care testing ,Biomedical Engineering ,030209 endocrinology & metabolism ,Bioengineering ,030204 cardiovascular system & hematology ,Sensitivity and Specificity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Prospective cohort study ,Aged ,Proinsulin ,Immunoassay ,business.industry ,Original Articles ,Middle Aged ,Early Diagnosis ,Endocrinology ,Diabetes Mellitus, Type 2 ,Point-of-Care Testing ,Biomarker (medicine) ,Female ,business ,Biomarkers - Abstract
Background:Intact proinsulin is a biomarker for pancreatic ß-cell dysfunction. In large prospective studies in nondiabetic subjects, elevated intact proinsulin predicted development of type 2 diabetes and/or macrovascular events up to 7 years in advance. This study was performed to evaluate a new semiquantitative lateral flow-based point-of-care rapid test (POCT) for elevated intact proinsulin (cutoff: 15 pmol/L). The test requires 10 µL of capillary whole blood, with visual readout after 5 minutes. It is best applied at 2 hours after a glucose challenge or a meal.Methods:POCT results were obtained by health care professionals from 60 patients and healthy subject (33 female, 27 male, 28 type 2 diabetes, age: 53.6 ± 12.3 years). An additional venous blood sample was obtained from all participants for measurement of intact proinsulin by means of a quantitative ELISA reference method (TecoMedical, Sissach, Switzerland).Results:Elevated intact proinsulin levels (>15 pmol/L) were determined by the reference method in 26 participants, of whom 22 were also positive with the POCT (sensitivity: 85%). All 34 subjects with low intact proinsulin levels were tested negative by the POCT (specificity: 100%).Conclusions:The test successfully detected elevated postprandial intact proinsulin levels in 85% of the tested subjects and no false positive test result occurred. This POCT can therefore serve as a simple screening tool for identification of patients with prevalent ß-cell dysfunction, who are at high risk for development of type 2 diabetes and/or macrovascular events within the next 5-7 years.
- Published
- 2016
17. Impact of a Noninvasive Blood Glucose Device on Glycemic Control and Daily Routine Measurement Aspects—Results of a Pilot Study
- Author
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Andreas Pfützner, Filiz Demircik, Alexander Lier, and Sanja Ramljak
- Subjects
medicine.medical_specialty ,Meal ,business.industry ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Home use ,medicine.disease ,Treatment satisfaction ,Diabetes mellitus ,Internal Medicine ,Physical therapy ,Medicine ,In patient ,business ,Daily routine ,Glycemic - Abstract
Regular blood glucose self-testing is considered to be the most painful procedure during daily treatment routine for patients with diabetes mellitus. This pilot study was undertaken to evaluate the performance of TensorTip CoG, a non-invasive glucose monitoring device (NI-CoG, CNOGA Medical, Israel) on glycemic control and daily measurement aspects in patients with type 1 and type 2 diabetes. The study was performed with 6 type 1 patients (T1D: 3 male/3 female, age: 43±16 years, HbA1c: 8.0±0.5%), and 15 type 2 patients (T2D: 8 male/7 female, 62±6 years, 7.2±1.3%). The participants used the NI-CoG device at home after an initial standardized meal experiment to evaluate device performance in comparison to a standard reference method (YSI Stat2300 plus). In addition, HbA1c was assessed and a treatment satisfaction questionnaire was completed after a period of three months of home use. During the meal experiment, NI-CoG showed good accuracy (mean bias: 15.3%; consensus error grid: 100% in zones A and B). A trend for HbA1c improvement was seen in both groups over 3 months (T1D: -0.22%, T2D: -0.1%, n.s.). Patients reported to measure more frequently, and to feel more comfortable with the non-invasive measurement procedure. Use of the device in the study initiated the general desire to switch to the new device also for daily routine use. The non-invasive TensorTip device was shown to increase the frequency of glucose testing and to have a positive impact on patients' perception of the measurement procedure. There was also an initial trend for improvements of glycemic control within the first three months of use in this pilot study. Disclosure A. Pfützner: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Lifecare. Speaker's Bureau; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim GmbH. A. Lier: None. S. Ramljak: None. F. Demircik: None.
- Published
- 2018
18. Noninvasive Tissue Glucose Prediction in Patients with Type 1 Diabetes
- Author
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Alexander Lier, Filiz Demircik, Sanja Ramljak, and Andreas Pfützner
- Subjects
Type 1 diabetes ,medicine.medical_specialty ,Continuous glucose monitoring ,business.industry ,Standard meal ,Endocrinology, Diabetes and Metabolism ,Glucose meter ,Insulin ,medicine.medical_treatment ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,medicine.disease ,Mean difference ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,In patient ,business ,Treatment monitoring - Abstract
Background: Pain-free assessment of the glucose information required for treatment monitoring is one of the most desired unmet medical needs in insulin treated patients with type 1 diabetes. TensorTip CoG, is a non-invasive tissue glucose monitoring device (NI-CoG) with an additional built-in invasive glucose meter (Inv-CoG), which operates based on optical methods in the near-infrared and visible wavelength range. Here we report about the results obtained from type 1 patients in the course of two clinical studies. Methods: The data from 6 patients with type 1 diabetes (3 male/3 female, age: 43±16 years, HbA1c: 8.0±0.5%), who had participated in a standard meal study experiment, and the results from 29 type 1 patients, who had participated in a system accuracy evaluation in accordance with ISO15197:2015 (13 male/16 female, age: 42±14 years, HbA1c: 7.5±0.5%) were combined for this analysis. Results: The meal study patients (n = 66 data points) and the ISO study patients (n = 29) showed good agreement of the NI-CoG predicted tissue glucose with the capillary reference method (YSI Stat2300 plus). Mean absolute relative difference (values >100 mg/dL) was calculated to be 13.3% (mean absolute difference for values Conclusions: The results of this new non-invasive glucose prediction device are encouraging for routine use in patients with type type 1 diabetes. This non-invasive technology has reached an accuracy level for glucose prediction that is comparable to the results published for needle sensors working for flash or continuous glucose monitoring. Disclosure A. Pfützner: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Lifecare. Speaker's Bureau; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim GmbH. F. Demircik: None. A. Lier: None. S. Ramljak: None.
- Published
- 2018
19. Advances in Patient Self-Monitoring of Blood Glucose
- Author
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Andreas Pfützner
- Subjects
Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,030209 endocrinology & metabolism ,Bioengineering ,03 medical and health sciences ,0302 clinical medicine ,Blood Glucose Self-Monitoring ,Internal Medicine ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Analysis method ,Daily routine ,American diabetes association ,Blood glucose monitoring ,medicine.diagnostic_test ,business.industry ,Original Articles ,Performance results ,Emergency medicine ,Self-monitoring ,business - Abstract
In 2 articles of the present issue, Bendini et al report about performance results obtained with 2 blood glucose monitoring systems of the Contour Next platform. Using several analysis methods, the authors demonstrate a very high accuracy, which meets all actual regulatory performance criteria. With consistent MARD results < 5% under daily routine conditions, this meter platform is finally fulfilling the accuracy request as set forth by the American Diabetes Association already in the late 1980s. This meter platform is representative for the successful effort of the device manufacturers who were consequently improving the analytical performance of blood glucose meters during the Past 2 decades, starting with an MARD of 12-15% at the end of the past century and reaching an excellent accuracy < 5% today.
- Published
- 2015
20. Patients’ Preferences for Insulin Injection Devices: Analysis of the Article by Pohlmeier et al
- Author
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Andreas Pfützner
- Subjects
Male ,medicine.medical_specialty ,ease of learning ,Endocrinology, Diabetes and Metabolism ,Injections, Subcutaneous ,Biomedical Engineering ,Insulin Glargine ,030209 endocrinology & metabolism ,Bioengineering ,Context (language use) ,02 engineering and technology ,Type 2 diabetes ,SoloSTAR ,Treatment satisfaction ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,medicine ,Insulin ,Humans ,Hypoglycemic Agents ,Intensive care medicine ,Insulin injection ,Disposable Equipment ,Aged ,Insulin glargine ,business.industry ,Syringes ,Small sample ,Usability ,Patient Preference ,Original Articles ,Middle Aged ,021001 nanoscience & nanotechnology ,medicine.disease ,Patient preference ,Diabetes Mellitus, Type 2 ,Patient Satisfaction ,Female ,0210 nano-technology ,business ,medicine.drug ,ease of use - Abstract
Background: Insulin glargine 300 U/mL (Gla-300) contains the same active ingredient as glargine 100 U/mL (Gla-100), and provides the same number of units in one-third of the volume. The SoloSTAR® injector pen has been modified to ensure accurate administration of this reduced volume and to improve user experience. Methods: Insulin- and pen-naïve adults with type 2 diabetes (T2DM) inadequately controlled with oral antihyperglycemic drugs, who had glycated hemoglobin (HbA1c) levels of 7.0-11.0 % (53-97 mmol/mol) were studied. They received once-daily Gla-300 in this 4-week, multicenter, open-label, single-arm study (NCT02227212). Ease of use/ease of learning (the primary endpoint), glycemic control, safety, and reliability of the disposable (prefilled) Gla-300 injector pen (secondary endpoints) were evaluated. Results: At week 4, 95.0% of 40 participating subjects assessed the pen as excellent/good and none as poor/very poor; 97.5% would recommend it to others. Total Diabetes Treatment Satisfaction Questionnaire scores were stable throughout the study. Mean (SD) fasting plasma glucose levels decreased from 166.1 (35.0) mg/dL at baseline to 124.2 (41.1) mg/dL at week 4. No product technical complaints (PTCs) or adverse events (AEs) related to PTCs were reported. The number of subjects experiencing hypoglycemic events of any kind and the incidence of AEs were low. No serious AEs were reported. Conclusions: The Gla-300 injector pen is easy to use and easy to learn to use, with demonstrable reliability and high degrees of acceptance and treatment satisfaction. Once-daily Gla-300 basal insulin treatment was well tolerated and effective in pen- and insulin-naïve adult T2DM subjects.
- Published
- 2017
21. Effect of linagliptin compared with glimepiride on postprandial glucose metabolism, islet cell function and vascular function parameters in patients with type 2 diabetes mellitus receiving ongoing metformin treatment
- Author
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Ernestos Anastassiadis, Andreas Pfützner, Thomas Forst, Stephan Diessel, and Andrea Löffler
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,medicine.disease ,Linagliptin ,Glucagon ,Metformin ,Glimepiride ,Endocrinology ,Postprandial ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,business ,medicine.drug ,Proinsulin - Abstract
Background The goal of this study was to investigate the effects of linagliptin compared with glimepiride on alpha and beta cell function and several vascular biomarkers after a standardized test meal. Methods Thirty-nine patients on metformin alone (age, 64 ± 7 years; duration of type 2 diabetes mellitus, 7.8 ± 4.5years, 27 male, 12 female; HbA1c, 57.2 ± 6.9 mmol/mol; mean ± SD) were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin, intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic guanosinmonophosphat and asymetric dimethylarginin levels were measured in the fasting state and postprandial at 30-min intervals for a duration of 5 h. The areas under the curve (AUC0−300 min) were calculated for group comparisons. Results HbA1c, fasting and postprandial glucose levels improved in both groups. An increase in postprandial insulin (22595 ± 5984 pmol/L*min), postprandial intact proinsulin (1359 ± 658 pmol/L*min), postprandial glucagon (317 ± 1136 pg/mL*min) and postprandial PAI-1 levels (863 ± 467 ng/mL*min) could be observed during treatment with glimepiride, whereas treatment with linagliptin was associated with a decrease in postprandial insulin (−8007 ± 4204 pmol/L*min), intact proinsulin (−1771 ± 426 pmol/L*min), postprandial glucagon (−1597 ± 1831 pg/mL*min) and PAI-1 levels (−410 ± 276 ng/mL*min). Conclusions Despite an improvement in blood glucose control in both groups, linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels. These results indicate an improvement in postprandial alpha and beta cell function, as well as a reduced postprandial vascular risk profile during treatment with linagliptin. Copyright © 2014 John Wiley & Sons, Ltd.
- Published
- 2014
22. Assessment for ease of use and preference of a new prefilled insulin pen (FlexTouch Degludec U100/U200) versus the SoloSTAR insulin pen by patients with diabetes and healthcare professionals
- Author
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Andreas Pfützner, Thomas Forst, Timothy L. Bailey, and Marcus Niemeyer
- Subjects
Adult ,Male ,Insulin degludec ,medicine.medical_specialty ,Health Personnel ,Nurses ,Pharmaceutical Science ,Type 2 diabetes ,Injections ,Drug Delivery Systems ,Physicians ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Hypoglycemic Agents ,Injection force ,Aged ,Cross-Over Studies ,Health professionals ,business.industry ,Insulin pen ,Patient Preference ,Middle Aged ,medicine.disease ,Crossover study ,Insulin, Long-Acting ,Diabetes Mellitus, Type 1 ,Endocrinology ,Diabetes Mellitus, Type 2 ,Basal (medicine) ,Female ,business - Abstract
FlexTouch® (FT) is a new prefilled insulin pen with no push-button extension and a low injection force used to deliver several basal insulins, including insulin degludec across a wide dose range (1 - 80 units with FT 100 IU/ml [FT100] and 2 - 160 units with 200 IU/ml [FT200]). This study was carried out to evaluate whether the novel features of FT affect the preferences of the device among patients with diabetes and healthcare professionals compared with the widely used SoloSTAR® pen.A multicenter, randomized, open-label, crossover study compared FT100 and FT200 with SoloSTAR. The study included patients with either type 1 (n = 22) or type 2 diabetes (n = 42), nurses (n = 32) and physicians (n = 32). Subjects were randomized to test each of the FT100, FT200 and SoloSTAR pens in a crossover set up. Subjects performed injections into a foam cushion at 4 - 6 different doses per device (2, 20, 40, 80, 120 and 160 IU).Overall, a significantly higher proportion of subjects, including dexterity-impaired and pen-naive patients, preferred to use FT100 (93.0%; 119/128) and FT200 (91.4%; 117/128) compared with 2.3% (3/128) and 3.9% (5/128) who preferred SoloSTAR (p0.001), respectively.FT100 and FT200 were preferred over SoloSTAR by nurses, physicians and patients with diabetes. This may be due to the novel design of FT, which improves ease of use, preference and confidence in delivering a complete, accurate dose of insulin, even at high doses.
- Published
- 2014
23. Evaluation of the Effects of Insufficient Blood Volume Samples on the Performance of Blood Glucose Self-Test Meters
- Author
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Thomas Forst, Jochen Sieber, Andreas Pfützner, Frank Flacke, PB Musholt, Sanja Ramljak, and Christina Schipper
- Subjects
Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Blood volume ,Roche Diagnostics ,Sample volume ,Patient Education as Topic ,Blood Glucose Self-Monitoring ,Diabetes Mellitus ,Internal Medicine ,Humans ,Medicine ,Metre ,Blood Volume ,business.industry ,Glucose meter ,Reproducibility of Results ,Correct response ,Surgery ,Original Article ,business ,Self test ,Biomedical engineering - Abstract
Background: Accuracy of blood glucose readings is (among other things) dependent on the test strip being completely filled with sufficient sample volume. The devices are supposed to display an error message in case of incomplete filling. This laboratory study was performed to test the performance of 31 commercially available devices in case of incomplete strip filling. Methods: Samples with two different glucose levels (60–90 and 300–350 mg/dl) were used to generate three different sample volumes: 0.20 μl (too low volume for any device), 0.32 μl (borderline volume), and 1.20 μl (low but supposedly sufficient volume for all devices). After a point-of-care capillary reference measurement (StatStrip, NovaBiomedical), the meter strip was filled (6x) with the respective volume, and the response of the meters (two devices) was documented (72 determinations/meter type). Correct response was defined as either an error message indicating incomplete filling or a correct reading (±20% compared with reference reading). Results: Only five meters showed 100% correct responses [BGStar and iBGStar (both Sanofi), ACCU-CHEK Compact+ and ACCU-CHEK Mobile (both Roche Diagnostics), OneTouch Verio (LifeScan)]. The majority of the meters (17) had up to 10% incorrect reactions [predominantly incorrect readings with sufficient volume; Precision Xceed and Xtra, FreeStyle Lite, and Freedom Lite (all Abbott); GlucoCard+ and GlucoMen GM (both Menarini); Contour, Contour USB, and Breeze2 (all Bayer); OneTouch Ultra Easy, Ultra 2, and Ultra Smart (all LifeScan); Wellion Dialog and Premium (both MedTrust); FineTouch (Terumo); ACCU-CHEK Aviva (Roche); and GlucoTalk (Axis-Shield)]. Ten percent to 20% incorrect reactions were seen with OneTouch Vita (LifeScan), ACCU-CHEK Aviva Nano (Roche), OmniTest+ (BBraun), and AlphaChek+ (Berger Med). More than 20% incorrect reactions were obtained with Pura (Ypsomed), GlucoCard Meter and GlucoMen LX (both Menarini), Elite (Bayer), and MediTouch (Medisana). Conclusions: In summary, partial and incomplete blood filling of glucose meter strips is often associated with inaccurate reading. These findings underline the importance of appropriate patient education on this aspect of blood glucose self-monitoring.
- Published
- 2013
24. A New Metabolite Panel Test for Identification of Patients With Impaired Glucose Tolerance? Analysis of the Article by Cobb et al
- Author
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Andreas Pfützner
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Metabolite ,Biomedical Engineering ,Bioengineering ,medicine.disease ,CobB ,Bioinformatics ,Test (assessment) ,Impaired glucose tolerance ,Identification (information) ,Blood draw ,chemistry.chemical_compound ,Endocrinology ,Insulin resistance ,chemistry ,Internal medicine ,Internal Medicine ,medicine ,Oral glucose tolerance ,business - Abstract
The article by Cobb et al represents solid research work applying the most sophisticated laboratory technologies, a very sound clinical research methodology, and valid statistical analysis procedures. The authors have identified a combination of metabolites suitable to replace the oral glucose tolerance test procedure in the identification of patients with impaired glucose tolerance (IGT) from a fasting blood draw. However, the discussed pathophysiological, clinical, and economic aspects may induce mechanisms restricting the probability of a global acceptance of this test for daily routine.
- Published
- 2014
25. Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes mellitus
- Author
-
Thomas Forst and Andreas Pfützner
- Subjects
endocrine system diseases ,Pharmacology ,Hypoglycemia ,Bioinformatics ,Glucagon-Like Peptide-1 Receptor ,Lixisenatide ,chemistry.chemical_compound ,Receptors, Glucagon ,Animals ,Humans ,Hypoglycemic Agents ,Medicine ,Pharmacology (medical) ,Glucagon-like peptide 1 receptor ,Glycemic ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,General Medicine ,medicine.disease ,Clinical trial ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,chemistry ,Tolerability ,Metabolic control analysis ,Peptides ,business - Abstract
The global prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing and is associated with a high risk of microvascular and macrovascular complications. Although some glucose-lowering therapies are associated with hypoglycemia and weight gain, glucagon-like peptide-1 (GLP-1) receptor agonists represent a significant advance in the treatment of T2DM, as they provide effective glycemic control with a low incidence of hypoglycemia and a beneficial effect on body weight, as well as potential improvements in cardiovascular outcomes.This article evaluates the pharmacological and clinical profile of the once-daily prandial GLP-1 receptor agonist lixisenatide for the treatment of T2DM.Once-daily prandial lixisenatide has been evaluated in an extensive clinical trials program, in which it was shown to have a favorable safety and tolerability profile, and to effectively improve metabolic control. The unique pharmacological properties of lixisenatide clearly differentiate it from other GLP-1 receptor agonists. As a once-daily agonist with a high affinity for the GLP-1 receptor, lixisenatide improves overall glycemic control, with particularly strong effects on postprandial plasma glucose levels. These attributes encourage the application of lixisenatide in those patients with extensive postprandial glucose excursions, or in combination with other antidiabetic drugs that have prevailing effects on fasting glucose levels.
- Published
- 2013
26. Technical Aspects of the Parkes Error Grid
- Author
-
Andreas Pfützner, Scott Pardo, David C. Klonoff, and Joan Lee Parkes
- Subjects
Blood Glucose ,business.industry ,Computer science ,Blood Glucose Self-Monitoring ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,computer.software_genre ,Grid ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Reference Values ,Reference values ,Practice Guidelines as Topic ,Internal Medicine ,Humans ,Original Article ,Artificial intelligence ,Data mining ,business ,Blood Glucose Measurement ,computer - Abstract
The Parkes error grid, which was developed in 1994, presented performance zones for blood glucose (BG) monitors with borders that were not mathematically specified at the time the grid was published.In this article, we (1) review the history of the Parkes error grid, (2) present the never-before-published exact coordinates and specifications of the grid so that others may produce an exact replica of the original grid, and (3) discuss our suggestions how this metric should be applied.The new ISO15197:2013 guideline for system accuracy assessment of BG meters for patient self-measurement incorporates use of this metric for defining acceptable accuracy of BG monitors. It is expected that, for regulatory purposes, this document will stipulate that the error grid version for type 1 diabetes should be applied with the caveat that only the A zone represents acceptable accuracy.It remains to be seen by how much the new error grid, which is currently being developed by the Food and Drug Administration/Diabetes Technology Society/American Diabetes Association/The Endocrine Society/Association for Advancement of Medical Instrumentation, will deviate from the Parkers error grid.
- Published
- 2013
27. Association of sulphonylurea treatment with all-cause and cardiovascular mortality: A systematic review and meta-analysis of observational studies
- Author
-
Andreas Pfützner, Axel Haupt, Gero Schwenk, Stephan Jacob, Thomas Forst, Guido Moeser, and Markolf Hanefeld
- Subjects
Risk ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Odds ratio ,Type 2 diabetes ,medicine.disease ,Confidence interval ,Surgery ,Sulfonylurea Compounds ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Diabetes mellitus ,Meta-analysis ,Internal medicine ,Cohort ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Observational study ,Cardiology and Cardiovascular Medicine ,business ,Cohort study - Abstract
We conducted a meta-analysis of cohort and case-control studies to evaluate all-cause and cardiovascular (CV) mortality of patients with type 2 diabetes mellitus (T2DM) who received sulphonylurea (SU) treatment, when compared to any other diabetes treatment. Only studies reporting raw data on mortality during SU treatment were included. Data were combined using random-effects (RE) models. Unadjusted odds ratios (ORs) are presented. Of 4991 publication titles and abstracts reviewed, 20 studies ( n = 551,912 patients) were included. For cohort studies ( n = 276,050), patients receiving SU monotherapy or combination treatment had significantly higher all-cause and CV mortality risks compared to any non-SU treatment [all-cause, 13 studies: OR = 1.92, 95% confidence interval (CI) = 1.48–2.49; CV, 5 studies: OR = 2.72, 95% CI = 1.95–3.79]. Validity was limited by the high treatment group heterogeneity ( I2 > 90%) and study-inherent biases/design differences. In conclusion, patients receiving SU treatment had increased all-cause and CV mortality risks. However, the meta-analysis was limited by the high heterogeneity of non-randomized studies.
- Published
- 2013
28. Clinical overview of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with Type 2 diabetes mellitus
- Author
-
Andreas Pfützner and Thomas Forst
- Subjects
business.industry ,Endocrinology, Diabetes and Metabolism ,Type 2 Diabetes Mellitus ,Dipeptidyl peptidase-4 inhibitor ,Pharmacology ,Hypoglycemia ,medicine.disease ,Linagliptin ,Clinical trial ,chemistry.chemical_compound ,Postprandial ,Pharmacokinetics ,chemistry ,Medicine ,Glycated hemoglobin ,business ,medicine.drug - Abstract
Linagliptin is a pharmacologically unique, orally active, once-daily dipeptidyl peptidase-4 inhibitor indicated for the treatment of hyperglycemia in patients with Type 2 diabetes mellitus. Compared with other dipeptidyl peptidase-4 inhibitors, linagliptin has a favorable pharmacokinetic profile with a primarily nonrenal route of elimination that avoids the need for dose adjustment in patients with renal impairment. When administered as monotherapy or in combination with other antihyperglycemic drugs, linagliptin treatment leads to clinically meaningful reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose levels. In addition, pancreatic β-cell function is enhanced. Linagliptin treatment is well tolerated, with weight-neutral effects and no increased risk of hypoglycemia. Of note, linagliptin treatment was associated with a significantly reduced risk of cardiovascular events in clinical trials of ≤2 years, although this finding remains to be confirmed in larger and longer clinical outcomes studies.
- Published
- 2013
29. Hematocrit Interference of Blood Glucose Meters for Patient Self-Measurement
- Author
-
Thomas Forst, John P. Lock, Sanja Ramljak, Martha E. Lyon, PB Musholt, Christina Schipper, and Andreas Pfützner
- Subjects
Blood Glucose ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Hematocrit ,Animal science ,Self measurement ,hemic and lymphatic diseases ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Hematocrit levels ,Oxygen pressure ,Blood glucose meters ,medicine.diagnostic_test ,business.industry ,Blood Glucose Self-Monitoring ,Surgery ,High Readings ,Original Article ,Normal blood ,Low hematocrit ,Artifacts ,business ,circulatory and respiratory physiology - Abstract
Background: Abnormal hematocrit levels may interfere with glucose readings of patient self-assessment blood glucose (BG) meters. The aim of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of BG meters applying different measurement technologies. Methods: Venous heparinized blood was manipulated to contain three different BG concentrations (50–90, 120–180, and 280–350 mg/dl) and five different hematocrit levels (25%, 35%, 45%, 55%, and 65%). After careful oxygenation to normal blood oxygen pressure (65–100 mmHg), each sample was measured (eight times) with the following devices: Accu-Chek® Aviva, Nano, and Active, Breeze®2 and Contour®, FreeStyle Freedom Lite®, GlucoDr. auto™, Glucofix® mio Plus, GlucoLab™, GlucoMen® LX Plus, Nova Max® Link, Nova Max® Plus, OneTouch® Ultra®2 and Verio®, On Call® Plus and Platinum, Optium Xceed®, Precision Xceed®, and TaiDoc Fora TD-4227. A YSI 2300 STAT Plus™ glucose analyzer served as reference method. Stability to hematocrit influence was assumed, with Results: Six of the investigated meters showed a stable performance in this investigation: Accu-Chek Active (7%), Glucofix mio Plus (5%), GlucoMen LX Plus (4%), NovaMax Plus (4%), Nova Max Link (7%), and OneTouch Verio (3%). All other meters failed this hematocrit interference test, with FreeStyle Freedom Lite (11%), and On Call Platinum 12%) being the better devices and On Call Plus (68%), GlucoLab (51%), TaiDoc Fora TD-4227 (39%), and Breeze 2 (38%) showing the worst performance. Conclusions: Hematocrit may affect BG meter performance in daily routine. In case of interference, low hematocrit values (
- Published
- 2013
30. Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus
- Author
-
Jochen Sieber, Bernd Stratmann, Andreas Pfützner, Harald Pohlmeier, Ludger Rose, Frank Flacke, Diethelm Tschoepe, and Klaus Funke
- Subjects
Adult ,Blood Glucose ,Male ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Insulin Glargine ,030209 endocrinology & metabolism ,Bioengineering ,Type 2 diabetes ,Hypoglycemia ,03 medical and health sciences ,0302 clinical medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,In patient ,030212 general & internal medicine ,Dosing ,Aged ,business.industry ,Insulin glargine ,Basal insulin ,Type 2 Diabetes Mellitus ,Original Articles ,Middle Aged ,medicine.disease ,Diabetes Mellitus, Type 2 ,Population study ,Female ,business ,Algorithm ,Algorithms ,medicine.drug - Abstract
The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% ( P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients.
- Published
- 2016
31. Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37
- Author
-
Dieter Hock, Andreas Pfützner, Hanns-Christian Tillmann, Wolf-Georg Forssmann, Ulf Forssmann, Kristin Forssmann, Berthold Hocher, Rudolf Richter, and Corrado Bernasconi
- Subjects
0301 basic medicine ,lcsh:Diseases of the circulatory (Cardiovascular) system ,medicine.medical_specialty ,endocrine system ,Injections, Subcutaneous ,030232 urology & nephrology ,Parathyroid hormone ,610 Medicine & health ,Pharmacology ,lcsh:RC870-923 ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Pharmacokinetics ,Calcium Metabolism Disorders ,Internal medicine ,Healthy volunteers ,lcsh:Dermatology ,medicine ,Humans ,Calcium metabolism ,Dose-Response Relationship, Drug ,business.industry ,General Medicine ,Middle Aged ,lcsh:RL1-803 ,lcsh:Diseases of the genitourinary system. Urology ,Healthy Volunteers ,Peptide Fragments ,030104 developmental biology ,Endocrinology ,Parathyroid Hormone ,lcsh:RC666-701 ,Nephrology ,Pharmacodynamics ,Calcium ,Female ,Institut für Ernährungswissenschaft ,Cardiology and Cardiovascular Medicine ,business ,hormones, hormone substitutes, and hormone antagonists ,Half-Life - Abstract
Background/Aims: Parathyroid hormone (PTH) derivatives exert pronounced renal and osteoanabolic properties when given intermittently. The current study was performed to assess the pharmacokinetic and pharmacodynamic properties as well as safety of subcutaneously applied PTH-1-37 after repeated dosing in healthy subjects. Methods: This randomized, double-blind, dose-escalating, placebo and active comparator controlled study was conducted in 33 healthy postmenopausal women. Subjects were allocated to one of five treatment options: 10, 20, or 40 µg PTH-1-37, 20 µg PTH-1-34 or placebo, administered as once daily subcutaneous doses for three days. Plasma drug concentrations and serum levels of endogenous PTH-1-84, and calcium as markers of biological activity were monitored during the treatment. Results: PTH was absorbed rapidly from the subcutaneous tissue with a median tmax of 30 minutes for 20 and 40 µg of PTH-1-37. tmax was 45 minutes for 20 µg PTH-1-34. Elimination half-lives were estimated as 76 ± 34 min and 70 ± 13 min for 20 µg and 40 µg PTH-1-37 (mean ± SD), and 78 ± 34 for 20 µg PTH-1-34. Both PTH fragments (PTH-1-37 and PTH-1-34) increased serum calcium. For PTH-1-37 the effect on serum calcium was dose-dependent. Suppression of endogenous PTH-1-84 was seen after the application of both PTH-1-37 and PTH-1-34. During the study period, the subjects experienced no unexpected or serious adverse events. Conclusions: PTH-1-37 is rapidly absorbed after s.c. injection, has a short plasma elimination half-life, and does not accumulate during multiple dosing. Biological activity was demonstrated by rising serum calcium and decreasing endogenous PTH-1-84 in blood plasma. The study drugs were well tolerated and safe. Our investigation presents data that PTH-1-37 is an excellent drug candidate for intervening with syndromes of dysregulation of calcium metabolism.
- Published
- 2016
32. In Type 2 Diabetes Patients, Insulin Glargine is Associated with Lower Postprandial Release of Intact Proinsulin Compared with Sulfonylurea Treatment
- Author
-
Stefan Pscherer, Berndt von Stritsky, Thomas Forst, Martin Larbig, and Andreas Pfützner
- Subjects
Blood Glucose ,Male ,endocrine system ,medicine.medical_specialty ,Time Factors ,endocrine system diseases ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Insulin Glargine ,Bioengineering ,Type 2 diabetes ,Insulin-Secreting Cells ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Aged ,Proinsulin ,Glycated Hemoglobin ,Dipeptidyl-Peptidase IV Inhibitors ,Insulin glargine ,business.industry ,Insulin ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,Middle Aged ,Postprandial Period ,medicine.disease ,Sulfonylurea ,Metformin ,Insulin, Long-Acting ,Cross-Sectional Studies ,Sulfonylurea Compounds ,Treatment Outcome ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,Drug Therapy, Combination ,Female ,Original Article ,business ,Biomarkers ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug - Abstract
Objective: Our objective was to investigate how postprandial processing of intact proinsulin is influenced by different pharmacological strategies in type 2 diabetes mellitus (T2DM). Materials/Methods: This exploratory, nonrandomized, cross-sectional study recruited T2DM patients and healthy subjects. Upon recruitment, eligible T2DM patients had been treated for ≥6 months with insulin glargine (GLA) plus metformin (MET), sulfonylureas (SU) plus MET, or dipeptidyl-peptidase-4 inhibitors (DPP-4-I) plus MET. Blood samples were drawn from study participants after an 8 h fast and at regular intervals for up to 5 h after consumption of a standardized meal. Study endpoints included postprandial intact proinsulin and insulin levels and the insulin/proinsulin ratio. Results: As expected, postprandial secretion of proinsulin was greater in all T2DM treatment groups than in healthy subjects (p < .01 for all comparisons). Postprandial release of proinsulin was significantly greater in T2DM patients treated with SU plus MET than in those treated with GLA plus MET (p = .003). Treatment with DPP-4-I plus MET was associated with reduced proinsulin secretion versus SU plus MET and an increased insulin/proinsulin ratio versus the other T2DM groups. Conclusions: Treatment of T2DM with GLA plus MET or DPP-4-I plus MET was associated with a more physiological postprandial secretion pattern of the β cell compared with those treated with SU plus MET.
- Published
- 2012
33. Clinical assessment of the accuracy of blood glucose measurement devices
- Author
-
Daniela Sachsenheimer, Michael Mitri, Marcus Borchert, Andrew Yap, PB Musholt, Andreas Pfützner, and Thomas Forst
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Type 2 diabetes ,Roche Diagnostics ,Diabetes mellitus ,medicine ,Humans ,Blood Glucose Measurement ,Aged ,Blood glucose meters ,business.industry ,Blood Glucose Self-Monitoring ,Insulin ,Healthy subjects ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Physical therapy ,Female ,business - Abstract
Blood glucose meters for patient self-measurement need to comply with the accuracy standards of the ISO 15197 guideline. We investigated the accuracy of the two new blood glucose meters BG*Star and iBG*Star (Sanofi-Aventis) in comparison to four other competitive devices (Accu-Chek Aviva, Roche Diagnostics; FreeStyle Freedom Lite, Abbott Medisense; Contour, Bayer; OneTouch Ultra 2, Lifescan) at different blood glucose ranges in a clinical setting with healthy subjects and patients with type 1 and type 2 diabetes. BGStar and iBGStar are employ dynamic electrochemistry, which is supposed to result in highly accurate results.The study was performed on 106 participants (53 female, 53 male, age (mean ± SD): 46 ± 16 years, type 1: 32 patients, type 2: 34 patients, and 40 healthy subjects). Two devices from each type and strips from two different production lots were used for glucose assessment (∼200 readings/meter). Spontaneous glucose assessments and glucose or insulin interventions under medical supervision were applied to perform measurements in the different glucose ranges in accordance with the ISO 15197 requirements. Sample values50 mg/dL and400 mg/dL were prepared by laboratory manipulations. The YSI glucose analyzer (glucose oxidase method) served as the standard reference method which may be considered to be a limitation in light of glucose hexokinase-based meters.For all devices, there was a very close correlation between the glucose results compared to the YSI reference method results. The correlation coefficients were r = 0.995 for BGStar and r = 0.992 for iBGStar (Aviva: 0.995, Freedom Lite: 0.990, Contour: 0.993, Ultra 2: 0.990). Error-grid analysis according to Parkes and Clarke revealed both 100% of the readings to be within the clinically acceptable areas (Clarke: A + B with BG*Star (100 + 0), Aviva (97 + 3), and Contour (97 + 3); and 99.5% with iBG*Star (97.5 + 2), Freedom Lite (98 + 1.5), and Ultra 2 (97.5 + 2)).This study demonstrated the very high accuracy of BG*Star, iBG*Star, and the competitive blood glucose meters in a clinical setting.
- Published
- 2012
34. Cardiovascular Benefits of GLP-1-BasedTherapies in Patients with Diabetes Mellitus Type 2: Effects on Endothelial and Vascular Dysfunction beyond Glycemic Control
- Author
-
Andreas Pfützner, Thomas Forst, and Matthias M. Weber
- Subjects
Blood Glucose ,lcsh:Internal medicine ,medicine.medical_specialty ,lcsh:Specialties of internal medicine ,Endocrinology, Diabetes and Metabolism ,lcsh:Medicine ,Incretin ,Review Article ,Type 2 diabetes ,Diabetic angiopathy ,Bioinformatics ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,lcsh:RC581-951 ,Glucagon-Like Peptide 1 ,Diabetes mellitus ,Internal medicine ,Humans ,Hypoglycemic Agents ,Medicine ,lcsh:RC31-1245 ,Glycemic ,Dipeptidyl-Peptidase IV Inhibitors ,lcsh:RC648-665 ,business.industry ,lcsh:R ,Body Weight ,Glucagon secretion ,Type 2 Diabetes Mellitus ,General Medicine ,medicine.disease ,Glucagon-like peptide-1 ,Endocrinology ,Diabetes Mellitus, Type 2 ,Endothelium, Vascular ,business ,Diabetic Angiopathies - Abstract
Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes. Beside more or less comparable glucose lowering efficacy, some of them have shown limited or probably even unfavorable effects on the cardiovascular system and overall mortality. Recently, incretin-based therapies (GLP-1 receptor agonists and DPP-IV inhibitors) have been introduced in the treatment of T2DM. Beside the effects of GLP-1 on insulin secretion, glucagon secretion, and gastrointestinal motility, recent studies suggested a couple of direct cardiovascular effects of GLP-1-based therapies. The goal of this paper is to provide an overview about the current knowledge of direct GLP-1 effects on endothelial and vascular function and potential consequences on the cardiovascular outcome in patients with T2DM treated with GLP-1 receptor agonists or DPP-IV inhibitors.
- Published
- 2012
35. Analysis of the Environmental Impact of Insulin Infusion Sets Based on Loss of Resources with Waste
- Author
-
Thomas Forst, Andreas Pfützner, Nils H. Nilsson, PB Musholt, and Bjoern Malmgren-Hansen
- Subjects
Insulin pump ,Conservation of Natural Resources ,business.product_category ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Bioengineering ,Environmental pollution ,Paper cup ,Environment ,Medical Waste ,Toxicology ,Insulin infusion ,Insulin Infusion Systems ,Internal Medicine ,medicine ,Humans ,Insulin ,Symposium ,business.industry ,Subcutaneous insulin ,Biotechnology ,Soft drink ,Annual loss ,business - Abstract
Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires regular change of infusion sets every 2-3 days in order to minimize the risk of skin irritations or other adverse events. This has been discussed to be a potential burden to the environment. The purpose of this analysis was to perform an environmental assessment of insulin pump infusion sets based on loss of resources occurring during incineration of the discarded products and by means of a lifecycle concept used to weight a material in relation to its rareness on earth and its consumption. In addition to five infusion sets (Inset30, InsetII, Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this analysis. The annual loss in waste of the so called “person reserve” of 3 days of catheter use was compared with daily consumption of a cup of coffee in a disposable paper cup and to a soft drink in an aluminum can. The weight-based loss in resources through waste for the infusion sets (except for Cleo) corresponded to 70-200% of the loss of resources for a coffee cup (Cleo, 320%; Omnipod, 1,821,600%) and to 1-3% of the loss from an aluminum soft drink can (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used in insulin pump therapy appears to be low and is similar to the burden induced by the uptake of one cup of coffee per day. The loss or resources with regular CSII is considerably lower than the loss or resources induced by patch pumps.
- Published
- 2011
36. Review of approved pioglitazone combinations for type 2 diabetes
- Author
-
Andreas Pfützner, Markolf Hanefeld, and Thomas Forst
- Subjects
Blood Glucose ,endocrine system diseases ,Combination therapy ,Anti-Inflammatory Agents ,Type 2 diabetes ,Pharmacology ,Hypoglycemia ,Bioinformatics ,Insulin resistance ,medicine ,Humans ,Hypoglycemic Agents ,Pharmacology (medical) ,Pioglitazone ,business.industry ,nutritional and metabolic diseases ,Type 2 Diabetes Mellitus ,General Medicine ,Prognosis ,medicine.disease ,Search terms ,Diabetes Mellitus, Type 2 ,Expert opinion ,Drug Therapy, Combination ,Thiazolidinediones ,Insulin Resistance ,business ,medicine.drug - Abstract
Pioglitazone is approved in combination with several other blood-glucose-lowering drugs for the treatment of type 2 diabetes mellitus (T2DM). Beyond lowering blood glucose levels, each combination of different blood-glucose-lowering drugs for the treatment of T2DM evolves specific pleiotropic effects, which might be considered on an individual basis in a certain patient.The objective of this article is to provide a short review of the pathophysiology of T2DM and to provide a rationale for the combination of pioglitazone with other antidiabetic drugs, based on a pathophysiological understanding of T2DM. Therefore, a PubMed search was undertaken covering the search terms 'pioglitazone', 'antidiabetic drugs' and 'combination therapy'.Treatment with pioglitazone in T2DM was shown to improve insulin resistance and blood glucose levels without increasing the risk of hypoglycemia. Beyond those metabolic activities, pioglitazone was shown to evolve anti-inflammatory and anti-atherogenic effects. It seems useful to combine different antidiabetic drugs based on the specific needs and contraindications in an individual patient. The treating of T2DM patients by addressing not only glucose control, but also the underlying pathophysiological etiology might help to improve patient prognosis in the long run, especially with regard to the vascular complications.
- Published
- 2011
37. Reduction of Postprandial Glycemic Excursions in Patients with Type 1 Diabetes: A Novel Human Insulin Formulation versus a Rapid-Acting Insulin Analog and Regular Human Insulin
- Author
-
Patrick Simms, Andreas Pfützner, Lutz Heinemann, Frank Flacke, Kerstin Albus, Marcus Hompesch, Solomon S. Steiner, and Rody Pohl
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Bioengineering ,Absorption ,Subcutaneous injection ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Insulin ,Insulin lispro ,Glycemic ,Type 1 diabetes ,Meal ,Insulin Lispro ,business.industry ,Middle Aged ,Postprandial Period ,medicine.disease ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Endocrinology ,Postprandial ,Area Under Curve ,Female ,Original Article ,business ,medicine.drug - Abstract
Evaluation of postprandial glycemic excursions in patients with type 1 diabetes with three prandial insulins: VIAject™ (Linjeta™), an ultra-fast insulin (UFI); insulin lispro (LIS); and regular human insulin (RHI).After stabilization of preprandial glycemia, 18 patients received a subcutaneous injection with an individualized insulin dose prior to a meal.Injection of UFI resulted in a more rapid insulin absorption than with either LIS or RHI (time to half-maximal insulin levels: 13.1 ± 5.2 vs 25.4 ± 7.6 and 38.4 ± 19.5 min; p = .001 vs LIS and p.001 vs RHI, LIS vs. RHI p.001). Maximal postprandial glycemia was lower with UFI (0-180 min; 157 ± 30 mg/dl; p = .002 vs RHI) and LIS (170 ± 42 mg/dl; p = .668 vs RHI) than after RHI (191 ± 46 mg/dl; RHI vs LIS p = .008). The difference between maximum and minimum glycemia was smaller with UFI (70 ± 17 mg/dl) than with either RHI (91 ± 33 mg/dl; p = .007 vs UFI) or LIS (89 ± 18 mg/dl; p = .011 vs UFI). Also, the area under the blood glucose profile was lower with UFI than with RHI (0-180 min; 21.8 ± 5.8 vs 28.4 ± 7.6 g·min/dl; p.001).The rapid absorption of UFI results in a reduction of postprandial glycemic excursions.
- Published
- 2011
38. The Fixed Combination of Pioglitazone and Metformin Improves Biomarkers of Platelet Function and Chronic Inflammation in Type 2 Diabetes Patients: Results from the PIOfix Study
- Author
-
M. Löbig, Thomas Forst, PB Musholt, Jürgen Müller, Ute Lehmann, Winfried Fuchs, Andreas Pfützner, Thomas Schöndorf, and C. Hohberg
- Subjects
Blood Platelets ,Male ,medicine.medical_specialty ,Platelet Function Tests ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Inflammation ,Type 2 diabetes ,Ligands ,Gastroenterology ,Body Mass Index ,Proinflammatory cytokine ,Diabetes mellitus ,Internal medicine ,von Willebrand Factor ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Blood Coagulation ,Aged ,Pioglitazone ,business.industry ,Thromboxanes ,Type 2 Diabetes Mellitus ,Original Articles ,Middle Aged ,medicine.disease ,Metformin ,Sulfonylurea Compounds ,Endocrinology ,Diabetes Mellitus, Type 2 ,Biomarker (medicine) ,Female ,Thiazolidinediones ,medicine.symptom ,business ,Biomarkers ,medicine.drug - Abstract
Background: Type 2 diabetes mellitus (T2DM) is characterized by a proinflammatory and procoagulant condition. This study investigates the impact of a pioglitazone plus metformin therapy on biomarkers of inflammation and platelet activation in comparison to a treatment with glimepiride plus metformin. Methods: The study was designed as a multicenter, randomized, double-blinded two-arm trial. Patients with T2DM and dyslipidemia under metformin monotherapy with hemoglobin A1c value between 6.5% and 9.0% were eligible for trial participation. Blood was drawn at baseline and after 24 weeks of treatment from patients of five centers. Markers of inflammation and thrombocyte function (soluble CD40 ligand, thromboxane, vWillebrand factor, adhesion molecules, clotting reaction) were evaluated subsequently in a central laboratory. Results: A total of 46 patients were included in the final analyses. Mean (± standard deviation) age was 58.5 ± 9.0 years (13 women, 33 men; disease duration 6.3 ± 5.0 years; body mass index 32.0 ± 4.8 kg/m2). A total of 25 patients were treated with pioglitazone plus metformin, and 21 patients were in the glimepiride arm. There was a significant decline of E-selectin (-3.7 ± 4.8 ng/ml, p < .001 versus baseline), vWillebrand factor (−19.5 ± 32.0%, p < .05), and high-sensitivity C-reactive protein concentrations (−1.08 ± 0.91 mg/liter, p < .05) in the metformin + pioglitazone arm only (metformin + glimepiride, −0.5 ± 3.4 ng/ml, +1.4 ± 33.2%, + 0.08 ± 0.72 mg/liter, respectively, all not significant). Also, all other surrogate markers for platelet function and inflammation showed slight improvements in the metformin + pioglitazone arm but not in the metformin + glimepiride arm. Conclusions: The fixed metformin + pioglitazone combination treatment showed an overall improvement of laboratory surrogate markers, indicating improvement of platelet function and of chronic systemic inflammation, which was not seen with metformin + glimepiride.
- Published
- 2011
39. Pilot Study for Assessment of Optimal Frequency for Changing Catheters in Insulin Pump Therapy—Trouble Starts on Day 3
- Author
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Volkmar Schmid, Andreas Pfützner, Marcus Borchert, Thomas Forst, and C. Hohberg
- Subjects
Adult ,Blood Glucose ,Male ,Insulin pump ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Pilot Projects ,Bioengineering ,Kaplan-Meier Estimate ,Catheterization ,Young Adult ,Insulin Infusion Systems ,Surveys and Questionnaires ,Diabetes mellitus ,Blood Glucose Self-Monitoring ,Internal Medicine ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Polytetrafluoroethylene ,Skin ,Glycemic ,Type 1 diabetes ,business.industry ,Insulin ,Original Articles ,Middle Aged ,medicine.disease ,Surgery ,Catheter ,Diabetes Mellitus, Type 1 ,Female ,business - Abstract
Background: Continuous subcutaneous insulin infusion (CSII) by means of insulin pump devices is considered to be one of the most optimal therapies to achieve treatment targets in patients with diabetes mellitus. In CSII, the insulin is delivered through Teflon catheters or steel needle infusion sets, which need to be renewed on a regular basis. This pilot study was performed to investigate the optimal change frequency in daily practice and to explore potential problems that may occur when the sets are used for a more prolonged time than the recommended up to 72 hours of usage (Teflon catheters). Method: Twelve patients with type 1 diabetes participated in the trial [age (mean ± STD): 40.3 ± 12.6 years, body mass index: 26.2 ± 3.3 kg/m2, hemoglobin A1c: 6.7 ± 0.6%]. They were asked to wear their infusion set (Comfort™ or Silhouette®) for increasing periods of 1, 2, 3, 4, and 5 days. After each use, patients completed standardized questionnaires regarding technical and medical issues associated with infusion set use. A health care professional investigated the infusion sites and infusion sets and completed an “infusion set inspection” questionnaire. Blood glucose was measured and recorded to assess a potential Influence of duration of catheter use on glycemic control. Results: Infusion set and injection site problems (itching, bruising, swelling, and pain) started to occur in measurable amounts on the 3rd day of catheter use, and about 40% of patients reported significant issues when using a catheter for 5 days. In parallel, there was a consistent increase in mean daily blood glucose levels that correlated with the number of days of catheter use (e.g., day 1: 7. 5 ± 3.8 mmol/liter, day 3: 8.4 ± 4.2 mmol/liter, day 5: 9.0 ± 4.0 mmol/liter, day 7: 11.6 ± 2.2 mmol/liter, p < 0.05 vs day 1). Conclusions: Using the catheters for 2 days resulted in a safe and well-tolerated therapy. Clinically relevant adverse events started to occur during the 3rd day and their incidence increased constantly with longer use. This was associated with undesired changes in mean glycemic control. Data support the recommendation by the drug and device manufacturers that insulin pump catheters should only be used for 48–72 hours to avoid adverse events and potential metabolic deterioration.
- Published
- 2010
40. High-Sensitivity C-Reactive Protein Predicts Cardiovascular Risk in Diabetic and Nondiabetic Patients: Effects of Insulin-Sensitizing Treatment with Pioglitazone
- Author
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Thomas Schöndorf, Thomas Forst, Markolf Hanefeld, and Andreas Pfützner
- Subjects
medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Biomedical Engineering ,Bioengineering ,Inflammation ,Pharmacology ,Sensitivity and Specificity ,Insulin resistance ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Thiazolidinedione ,Pioglitazone ,business.industry ,Insulin ,Biomarkers of Diabetes ,Type 2 Diabetes Mellitus ,Atherosclerosis ,medicine.disease ,C-Reactive Protein ,Endocrinology ,Cardiovascular Diseases ,Thiazolidinediones ,medicine.symptom ,Rosiglitazone ,business ,Biomarkers ,medicine.drug - Abstract
Systemic inflammatory activity has turned out to play a key pathogenic role in vascular atherosclerosis, insulin resistance, and type 2 diabetes mellitus. Inflammatory biomarkers may therefore be a valuable tool for risk evaluation. Among them, the best evidence to date supports the use of high-sensitivity C-reactive protein (hs-CRP) to monitor insulin resistance and cardiovascular risk in diabetic and nondiabetic individuals. Data suggest that hs-CRP may also participate directly in the process of atherogenesis. A growing number of clinical trials tested the hypothesis that antidiabetic drugs specifically targeting insulin resistance could benefit individuals by reducing inflammation, atherogenesis, and thus cardiovascular risk. One such class are the thiazolidinediones (pioglitazone and rosiglitazone). These agents act as selective ligands of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). This article reviewed published data on hs-CRP changes with the thiazolidinedione agent pioglitazone. Here we found pronounced insulin-sensitizing and anti-inflammatory properties in different clinical settings, including diabetic and nondiabetic individuals. Coadministration of pioglitazone to antilipidemic statin therapy resulted in additional effects on low-grade inflammation, and hs-CRP reduction has been demonstrated to occur independently of glucose lowering. The anti-inflammatory effect appeared to be a rapid physiologic reaction on PPARgamma activation and could be observed within a short-term interval after starting pioglitazone therapy. In summary, clinical study results underline the benefit of an early insulin resistance treatment to oppose systemic vascular inflammation and cardiometabolic syndrome in patients with elevated levels of high-sensitivity C-reactive protein.
- Published
- 2010
41. Laboratory Evaluation of a New Lateral-Flow-Based Point-of-Care Rapid Test for Assessment of Chronic Systemic Inflammation
- Author
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Thomas Forst, Andreas Pfützner, Petra B. Mushholt, Robert Maurer, Matthias M. Weber, and Renate Siebenhaar
- Subjects
medicine.medical_specialty ,Point-of-Care Systems ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Systemic inflammation ,Gastroenterology ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Whole blood ,Macrovascular disease ,Point of care ,Inflammation ,biology ,business.industry ,Biomarkers of Diabetes ,C-reactive protein ,Liter ,medicine.disease ,Surgery ,C-Reactive Protein ,Chronic Disease ,biology.protein ,Biomarker (medicine) ,medicine.symptom ,business ,Biomarkers - Abstract
The determination of C-reactive protein (CRP) by means of a highly sensitive laboratory method as an independent biomarker for assessment of chronic systemic vascular inflammation and cardiovascular risk is recommended by therapeutic guidelines for diabetes and cardiovascular disease in the United States and in Europe. The purpose of this investigation was to investigate the specificity and sensitivity of a newly developed lateral-flow-based point-of-care (POC) rapid test with semi-quantitative visual reading in comparison with a laboratory reference standard method. The high-sensitivity CRP concentrations of 66 samples were determined by means of turbidimetry and the POC test (5 microl serum/10 microl capillary whole blood, 10 minutes) was independently performed by three investigators blinded to each other's results. The visual readings were classified, as recommended by the American Heart Association, to represent a low risk (0-1 mg/liter), moderate risk (1-3 mg/liter), or high risk (3-10 mg/liter) or to indicate an unspecific inflammation (10 mg/liter). According to the reference method, there were 17 samples in the low-risk group, 19 samples in the moderate-risk group, and 26 samples in the high-risk group, and 4 samples showed an unspecific inflammation. All three investigators reached very conclusive results. The range of agreement between the visual readings of the investigators and the laboratory method ranged between 94% and 97%. The sensitivity for assessment of moderate-to-high cardiovascular risk was 100% (45/45 were detected), and the specificity ranged between 90% and 95%. The newly developed lateral-flow-based POC rapid test showed an excellent agreement between individual visual reading and the laboratory reference method. It may therefore be suitable for a fast and convenient screening, which, after laboratory test confirmation, may help to identify patients with elevated risk of macrovascular disease.
- Published
- 2010
42. Dihydropyrimidine Dehydrogenase Genotyping and Phenotyping for 5- Fluorouracil Dysmetabolism: Moving Towards Personalized Chemotherapy in Patients with Cancer
- Author
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Moritz Eidens, Matthias M. Weber, Marco Klemm, Andreas Pfützner, Stefan Prause, and Alexander Weise
- Subjects
Pharmacology ,Oncology ,medicine.medical_specialty ,Chemotherapy ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Fluorouracil ,Internal medicine ,Genetics ,medicine ,Dihydropyrimidine dehydrogenase ,Molecular Medicine ,In patient ,business ,Molecular Biology ,Genotyping ,Genetics (clinical) ,medicine.drug - Published
- 2009
43. Postprandial Vascular Effects of VIAject Compared With Insulin Lispro and Regular Human Insulin in Patients With Type 2 Diabetes
- Author
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Philip Pichotta, Senait Forst, Andreas Pfützner, C. Hohberg, Thomas Forst, Eda Tarakci, Solomon S. Steiner, Alan Krasner, and Frank Flacke
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Emerging Treatments and Technologies ,Injections, Subcutaneous ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,Arginine ,chemistry.chemical_compound ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Insulin lispro ,Original Research ,Advanced and Specialized Nursing ,Insulin Lispro ,business.industry ,Microcirculation ,Nitrotyrosine ,digestive, oral, and skin physiology ,Middle Aged ,Postprandial Period ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,chemistry ,Blood Vessels ,Tyrosine ,Female ,Asymmetric dimethylarginine ,business ,Blood vessel ,medicine.drug - Abstract
OBJECTIVE Recent studies suggested an impact of prandial insulin delivery on postprandial regulation of tissue blood flow. This study compared the effect of VIAject with human regular insulin and insulin lispro on postprandial oxidative stress and endothelial function in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Fourteen patients (seven men; aged 61.5 ± 1.8 years; duration of diabetes 6.6 ± 4.6 years; A1C 7.2 ± 0.5% [mean ± SEM]) received a prandial injection of VIAject, human regular insulin, and insulin lispro. At baseline and after a standardized liquid meal test (Ensure Plus), the postprandial increases in asymmetric dimethylarginine (ADMA) and nitrotyrosine levels were investigated. In addition, the postprandial effects on microvascular blood flow, skin oxygenation, and vascular elasticity were measured. RESULTS Treatment with VIAject resulted in a significant reduction in the peak postprandial generation of ADMA compared with human insulin and insulin lispro (VIAject −27.3 ± 22.6, human insulin 97.7 ± 24.4, and insulin lispro 66.9 ± 33.9 nmol/l; P < 0.05, respectively). The postprandial increases in nitrotyrosine levels were significantly less after VIAject than after human regular insulin (VIAject −0.22 ± 0.17 vs. human insulin 0.25 ± 0.15 μg/ml; P < 0.05), whereas nitrotyrosine after insulin lispro was in between (insulin lispro 0.09 ± 0.07 μg/ml; NS). In parallel, earlier and more pronounced increases in microvascular blood flow and skin oxygenation were obtained after VIAject compared with those after human insulin or insulin lispro (P < 0.05, respectively). All insulin formulations resulted in comparable improvements in central arterial elasticity. CONCLUSIONS Treatment with VIAject reduced postprandial oxidative stress and improved endothelial function compared with human regular insulin or insulin lispro.
- Published
- 2009
44. FlexPen®for the delivery of insulin: accuracy, injection force and patient preference
- Author
-
Andreas Pfützner
- Subjects
medicine.medical_specialty ,business.industry ,Insulin ,medicine.medical_treatment ,Low dose ,Biomedical Engineering ,Dose accuracy ,General Medicine ,Patient preference ,Injections ,Drug Delivery Systems ,Patient perceptions ,Patient Satisfaction ,Surveys and Questionnaires ,Diabetes Mellitus ,medicine ,Humans ,Patient Compliance ,Surgery ,Medical physics ,business ,Injection force ,Biomedical engineering - Abstract
FlexPen® is a widely used, prefilled, insulin-delivery pen for patients with Type 1 or Type 2 diabetes. Well-designed trials suggest that FlexPen is more accurate than other prefilled pens at high, medium and low doses. Furthermore, FlexPen is preferred to the vial-and-syringe method by patients, but comparisons of patient preference for modern pens are currently lacking. Next Generation FlexPen® has similar accuracy to FlexPen but has improved patient perception. FlexPen improves adherence and reduces costs compared with the vial-and-syringe method, but the relative adherence and/or cost benefits of different pens are unknown. Important improvements in Next Generation FlexPen include: a significantly reduced injection force (that is lower than the injection force of other prefilled pens) and clearer labeling for insulin-type differentiation. Current evidence suggests that FlexPen and Next Generation FlexPen are an attractive choice when considering insulin-delivery methods.
- Published
- 2009
45. Reliability of Lightguide Spectrophotometry (O2C®) for the Investigation of Skin Tissue Microvascular Blood Flow and Tissue Oxygen Supply in Diabetic and Nondiabetic Subjects
- Author
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Eda Tarakci, Senait Forst, C. Hohberg, Peter H. Kann, Thomas Forst, and Andreas Pfützner
- Subjects
Neurological and Microvascular Function ,Muscle tissue ,Pathology ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Coefficient of variation ,Biomedical Engineering ,Bioengineering ,Oxygenation ,Blood flow ,medicine.disease ,medicine.anatomical_structure ,Diabetes mellitus ,Internal Medicine ,medicine ,Hemoglobin ,Nuclear medicine ,business ,Reactive hyperemia ,Thenar eminence - Abstract
Background and Aims: Skin microvascular assessment has progressed to an important evaluation in patients with diabetes mellitus. This study was done to evaluate a new device using micro-lightguide spectrophotometry in the assessment of skin microvascular function. Material and Methods: Twenty nondiabetic subjects (age 46.6 ± 14.8 years; mean ± SD) and 20 diabetic patients (age 59.4 ± 8.4 years) participated in repeated microvascular measurements using micro-lightguide spectrophotometry. This technique allows simultaneous, noninvasive measurement of microvascular blood flow and hemoglobin oxygenation (SO 2) at the same anatomical area in different tissue layers. A skin probe was placed on nonhairy skin at the thenar eminence of the left hand for the measurement of SO2, and the postischemic reactive hyperemia response (PRH) was measured in skin and underlying muscle tissue. Results: Repeated measurements in PRH revealed a good correlation at the superficial skin layer ( r = 0.97, p < 0.0001) with a coefficient of variation at 9.2 ± 1.7% and at the superficial muscle layer ( r = 0.80, p < 0.0002) with a coefficient of variation at 9.7 ± 1.5%. A slightly weaker correlation was observed for the SO 2 measurement at the skin layer (r = 0.69 ± p < 0.0001) with a coefficient of variation at 17.5 ± 3.8% and at the muscle layer ( r = 0.48; p = 0.0016) with a coefficient of variation at 18.1 ± 10.5%. Conclusions: Lightguide spectrophotometry is an easy, noninvasive, and reliable method for simultaneous measurement of superficial microvascular blood flow by laser Doppler fluxmetry and skin oxygenation by spectrophotometry. Further studies are required to clarify the validity of these measures in special patient populations such as diabetes mellitus with specified microvascular complications.
- Published
- 2008
46. Effects of pioglitazone and/or simvastatin on low density lipoprotein subfractions in non-diabetic patients with high cardiovascular risk: A sub-analysis from the PIOSTAT study
- Author
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Thomas Forst, Jens Pietzsch, Georg Lübben, Andreas Pfützner, E. Karagiannis, Jürgen Müller, Markolf Hanefeld, and W. Leonhardt
- Subjects
Adult ,Male ,Simvastatin ,medicine.medical_specialty ,Cohort Studies ,chemistry.chemical_compound ,Insulin resistance ,Double-Blind Method ,Risk Factors ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,Triglycerides ,Aged ,Pioglitazone ,biology ,Triglyceride ,business.industry ,Cholesterol ,Middle Aged ,medicine.disease ,Lipoproteins, LDL ,Treatment Outcome ,Endocrinology ,chemistry ,Cardiovascular Diseases ,Low-density lipoprotein ,HMG-CoA reductase ,biology.protein ,Drug Therapy, Combination ,Female ,Thiazolidinediones ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Lipoprotein - Abstract
Background We analyzed the efficacy and possible synergistic actions of pioglitazone and simvastatin monotherapy versus their combination on LDL subfractions from a subpopulation from the PIOSTAT three-arm randomized controlled trial. PPARγ agonists, such as pioglitazone, improve insulin sensitivity and glycemic control and appear to lower the concentration of atherogenic small dense LDL particles. Insulin resistance frequently occurs in non-diabetic patients with cardiovascular disease. Statins, such as simvastatin, reduce cardiovascular events by lowering LDL-C. So far, only scarce information exists for comparative efficacy and possible synergistic effects of combination therapy on LDL subfractions, cholesterol particle load, and particle number of atherogenic small dense LDL. Methods 125 non-diabetic patients with high cardiovascular risk were randomized to therapy with pioglitazone 45 mg/day, simvastatin 40 mg/day, or the combination of both, for 12 weeks. In the present sub-study, LDL subfractions from 88 patients were separated by very-fast ultracentrifugation. Results Simvastatin monotherapy significantly reduced cholesterol and triglyceride concentrations in IDL, LDL1, and LDL2. The lipid concentrations and lipid loads in LDL3 remained unchanged. By contrast, treatment with pioglitazone reduced the cholesterol concentration in LDL3 (density 1.040–1.066 kg/l) from 0.38 to 0.31 mmol/l ( p = 0.0004) and of the cholesterol load per particle from 1058 to 934 mol/mol ( p = 0.0149). Even greater reductions of cholesterol in LDL3 were observed with the combination of pioglitazone and simvastatin: from 0.38 to 0.29 mmol/l ( p = 0.0006) and from 1021 to 903 mol/mol ( p = 0.0011), respectively. In addition, combination therapy reduced the particle number of LDL3 from 356 to 316 nmol/l ( p = 0.0074). Conclusions Simvastatin preferentially lowered LDL1 and LDL2 subfractions, whereas pioglitazone reduced LDL3 cholesterol and cholesterol load. In addition, the combination reduced the LDL3 particle number. Thus, our data suggest a synergistic action of pioglitazone and simvastatin on atherogenicity of small dense LDL particles.
- Published
- 2008
47. Association of COLIA1 Sp1 polymorphism with the effect of subcutaneously injected recombinant hGH in GH-deficient adults
- Author
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Nils Habbe, Peter H. Kann, D. Ivan, Jochen R Ittner, Marlitt Haist, S. Meyer, Ursula Plöckinger, Peter P. Nawroth, Matthias M. Weber, Günter K. Stalla, Andreas Pfützner, Ulrich Tuschy, Alexander Weise, and S Schaefer
- Subjects
Adult ,Male ,medicine.medical_specialty ,Guanine ,Genotype ,Injections, Subcutaneous ,Dwarfism ,Collagen Type I ,Growth hormone deficiency ,law.invention ,law ,Internal medicine ,Genetics ,medicine ,Humans ,Prospective Studies ,Dwarfism, Pituitary ,Prospective cohort study ,Pharmacology ,Polymorphism, Genetic ,Human Growth Hormone ,business.industry ,Human growth hormone ,Homozygote ,Middle Aged ,medicine.disease ,Recombinant Proteins ,Endocrinology ,medicine.anatomical_structure ,Recombinant DNA ,Molecular Medicine ,Female ,business ,Pharmacogenetics ,Subcutaneous tissue - Abstract
Objective: Collagen type I is a common structural protein in bone and skin. Similar to its association with the mechanical properties of the skeleton and, thus, bone-fracture risk, the collagen type I α (COLIA)-1 specific protein (Sp)-1 polymorphism may be related to variations in the collagen type I-containing subcutaneous tissue and its biological properties. In this study, we analyzed a possible influence of the COLIA1 Sp1 polymorphism on the effect of subcutaneously injected recombinant human growth hormone (hGH) in GH-deficient adults. Materials & methods: We determined the COLIA1 Sp1 polymorphism in 122 adults with GH deficiency of different origin, who were derived from the prospective Pfizer International Growth Database (KIMS) Pharmacogenetics Study. Inclusion criteria were subcutaneous applied treatment with hGH for over 12 months, finished dose titration of hGH by following serum IGF-1 concentrations until desired levels were achieved, and centralized, standardized IGF-1 measurements. The genotypes (GG/GT/TT) were statistically related to clinical data from the KIMS database. Results: The dose of injected hGH was significantly related to the COLIA1 Sp1 genotypes (p = 0.049), whereby the GG homozygotes were treated with a significantly higher dose of hGH than TT homozygotes (p = 0.03). Accordingly, the IGF-1:GH ratios were significantly lower in GG compared with TT homozygotes (p = 0.04). Both groups showed no significant differences in their IGF-1 serum concentrations (p = 0.98) and IGF-1 SDS (p = 0.79). Conclusion: The COLIA1 Sp1 polymorphism is related to the dose of individually required, subcutaneous injected hGH in GH-deficient adults, probably because of an alteration of the subcutaneous collagen type I structure, content and/or biological/biomechanical properties. GG homozygotism, which is related to a more stable bone structure and decreased fracture risk, may impact skin resistance to subcutaneous injected protein-based drugs, as shown for hGH in this study.
- Published
- 2008
48. Prefilled insulin device with reduced injection force: patient perception and accuracy
- Author
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Christina Jørgensen, C Hohberg, L P F Frøkjaer, T. Reimer, and Andreas Pfützner
- Subjects
Accuracy and precision ,medicine.medical_specialty ,Patients ,business.industry ,Syringes ,Insulin ,medicine.medical_treatment ,Reproducibility of Results ,Dose accuracy ,General Medicine ,Specific density ,Surgery ,Insulin aspart ,Patient perceptions ,Surveys and Questionnaires ,medicine ,Humans ,business ,Injection force ,Biomedical engineering ,medicine.drug - Abstract
The injection force and the patient perception of the Next Generation FlexPen (NGFP) with design modifications aimed at reducing injection force was assessed. The accuracy and precision of the NGFP was also tested under standard conditions.Dosing accuracy was tested (according to ISO 11608 requirements) at 1 IU, 30 IU and 60 IU doses (acceptable limits were 1 +/- 1 IU (0-2 IU), 30 +/- 1.5 IU (28.5-31.5 IU), and 60 +/- 3 IU (57-63 IU)). Pens were tested at reference conditions (18-28 degrees C and relative humidity 25-75%). Delivered doses were measured on a sensitive balance and corrected for the specific density of the insulin aspart used (according to ISO 11608-1). Precision was calculated from the variance around the mean delivered dose. The injection force of NGFP was measured, and user-preference of NGFP and FlexPen (FP) were compared in 50 patients with type 2 diabetes.The mean injection force with NGFP and FP was 12.57 +/- 1.81 N and 17.90 +/- 1.51 N (p0.001), respectively. Almost twice as many patients rated the injection force as 'good' or 'very good' with NGFP (80%, 72% and 38% when delivering 20 IU, 40 IU and 60 IU, respectively) compared with FP (48%, 32% and 20% when delivering 20 IU, 40 IU and 60 IU, respectively) and 76% of patients rated NGFP as superior, in terms of simplicity and comfort, to FP. NGFP accurately delivered the set doses (means [SD] were 0.98 [0.06] IU, 29.98 [0.18] IU, and 59.93 [0.24] IU for the 1 IU, 30 IU and 60 IU doses, respectively).These results show that NGFP has a 30% reduction in injection force compared with FP and was rated as 'more simple and comfortable to use' by patients. Furthermore, NGFP was as accurate and as precise as FP.
- Published
- 2008
49. Differences in the Dose Accuracy of Insulin Pens
- Author
-
Johannes Pfützner, Heike Hänel, Wei Sun, Andreas Pfützner, Alexander Weise, and Nicole Thomé
- Subjects
business.industry ,Endocrinology, Diabetes and Metabolism ,Insulin ,medicine.medical_treatment ,Biomedical Engineering ,Dose accuracy ,Bioengineering ,Original Articles ,Type 2 diabetes ,medicine.disease ,Specific density ,Animal science ,Instructions for use ,Internal Medicine ,Medicine ,Dosing ,HumaPen ,business ,Insulin injection - Abstract
Background: Modern insulin injection pens provide a convenient and accurate way for diabetes patients to inject insulin. They have widespread use among children and adults with type 1 and type 2 diabetes in the U.S. and Europe. This study compared the dosing accuracy of four commonly available insulin pens (OptiClik ® and SoloSTAR ® from sanofi-aventis, FlexPen ® from Novo Nordisk, and HumaPen ® LUXURA™ from Eli Lilly). Methods: The dosing accuracy was tested for all pens with 24 x 10 IU and 9 x 30 IU injection volumes to investigate whether the pens complied with the acceptable International Organization for Standardization (ISO) limits of 10% (± 1 IU) for 10 IU and 5% (± 1.5 IU) for 30 IU. The doses were each applied with a new needle strictly according to the instructions for use by the pen manufacturers. A pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. Four insulin pens (two each from different production lots) were used for each of the two volumes, resulting in a total of 192 doses per pen with 10 IU, and 72 doses per pen with 30 IU. Results: FlexPen (mean absolute percent deviation for 10 IU and 30 IU: 1.64 ± 0.84% and 0.83 ± 0.26%, respectively) and HumaPen LUXURA (1.10 ± 0.20% and 0.62 ± 0.19%; not significant versus FlexPen for both doses) were more accurate than the OptiClik (4.78 ± 3.31% and 2.97 ± 2.48%, p
- Published
- 2008
50. Pleiotrophic and anti-inflammatory effects of pioglitazone precede the metabolic activity in type 2 diabetic patients with coronary artery disease
- Author
-
W. Dänschel, Andreas Pfützner, Gerhard Dikta, M. Morcos, Georg Lübben, E. Karagiannis, Thomas Forst, M. Drexler, C. Hohberg, Thomas Schöndorf, and M. Borchert
- Subjects
Blood Glucose ,Male ,Vasculitis ,medicine.medical_specialty ,Anti-Inflammatory Agents ,Placebo-controlled study ,Inflammation ,Coronary Artery Disease ,Type 2 diabetes ,Gastroenterology ,Placebos ,Coronary artery disease ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Hypoglycemic Agents ,Aged ,Pioglitazone ,business.industry ,Vascular disease ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,C-Reactive Protein ,Endocrinology ,Diabetes Mellitus, Type 2 ,Matrix Metalloproteinase 9 ,Female ,Thiazolidinediones ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,medicine.drug - Abstract
We investigated MMP-9 levels and inflammatory markers during pioglitazone treatment in type 2 diabetic patients with cardiovascular disease. In this randomized multicenter, double blinded, placebo controlled study, 92 type 2 diabetic patients with angiographically proven CHD were randomly assigned to pioglitazone or placebo treatment. At baseline and during a 28 days observational period MMP-9, MCP1, hsCRP, IL-6, sCD40, and P-selectin were monitored. During Pioglitazone treatment, a 12% reduction in MMP-9 and a 18% reduction in hsCRP levels (p < 0.05, respectively) could be observed already after 3 days. MCP-1 levels were reduced by 14% after 10 days of treatment (p < 0.0001). At the end of the study, these parameters were significantly lower in the pioglitazone group as compared to the placebo group (MMP-9: 392 ± 286 versus 427 ± 166 ng/ml; hsCRP: 1.9 ± 1.7 versus 3.1 ± 2.3 ng/L; MCP-1: 413 ± 115 versus 471 ± 146 pg/ml; p < 0.05, respectively). sCD40 levels decreased by 32.5% (p < 0.05) and P-selectin decreased by 3.2% (p = 0.053) in the pioglitazone group. No change could be found with regard to the other study endpoints. No changes in these parameters could be observed during placebo treatment. Even before effects on glucose metabolism could be obtained, pioglitazone exerts immediate effects on plasma markers of plaque vulnerability and inflammation.
- Published
- 2008
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