Author: "Elena Henkel" - Searchworks@Jio Institute Digital Library Search Results

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57 results on '"Elena Henkel"'

1. Sudomotor Testing of Diabetes Polyneuropathy

Author: Sarah-Maria Krieger, Manja Reimann, Rocco Haase, Elena Henkel, Markolf Hanefeld, and Tjalf Ziemssen
Subjects: diabetes, polyneuropathy, screening tool, sudomotor function, Sudoscan, Neurology. Diseases of the nervous system, RC346-429
Abstract: Objective: The performance of the Sudoscan technology for diagnosing diabetic polyneuropathy (DPN) was evaluated against the quantitative sudomotor axon reflex test (QSART). Furthermore, the association of Sudoscan with two clinical neuropathy scoring systems was evaluated.Methods: Forty-seven patients with type 2 diabetes (20 without DPN, 27 with DPN) and 16 matched controls were examined for neuropathic symptoms and for the extent of sensory deficits. Sweat latency and volume by QSART and the skin electrochemical conductance (ESC) by Sudoscan were measured.Results: The feet and hand ESC was significantly lower in patients with DPN as compared to controls. Patients with DPN had also lower hand ESC than patients without DPN. Sensitivity and specificity of feet and hand ESC for detecting DPN were 70/85% and 53/50% respectively. QSART could not differentiate between the three groups. ESC was inversely related to neuropathic symptoms and sensory impairment. ESC was significantly correlated with sensory impairment and pain.Conclusions: Sudoscan shows a good performance in detecting subjects with DPN and it correlates well with clinical signs and symptoms of neuropathy.Significance: This study provides evidence that Sudoscan has high potential to be used as screening tool for DPN and possibly also for small fiber neuropathy in diabetic patients.HIGHLIGHTS- The sudomotor function test Sudoscan shows a good performance to detect diabetes peripheral neuropathy.- Sudoscan measures significantly correlate with clinical signs and symptoms of neuropathy.- The Sudoscan technology may help to secure clinical diagnosis of small fiber neuropathy.
Published: 2018
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2. CRISPR/Cas9-mediated knockout of c-REL in HeLa cells results in profound defects of the cell cycle.

Author: Carsten Slotta, Thomas Schlüter, Lucia M Ruiz-Perera, Hussamadin M Kadhim, Tobias Tertel, Elena Henkel, Wolfgang Hübner, Johannes F W Greiner, Thomas Huser, Barbara Kaltschmidt, and Christian Kaltschmidt
Subjects: Medicine, Science
Abstract: Cervical cancer is the fourth common cancer in women resulting worldwide in 266,000 deaths per year. Belonging to the carcinomas, new insights into cervical cancer biology may also have great implications for finding new treatment strategies for other kinds of epithelial cancers. Although the transcription factor NF-κB is known as a key player in tumor formation, the relevance of its particular subunits is still underestimated. Here, we applied CRISPR/Cas9n-mediated genome editing to successfully knockout the NF-κB subunit c-REL in HeLa Kyoto cells as a model system for cervical cancers. We successfully generated a homozygous deletion in the c-REL gene, which we validated using sequencing, qPCR, immunocytochemistry, western blot analysis, EMSA and analysis of off-target effects. On the functional level, we observed the deletion of c-REL to result in a significantly decreased cell proliferation in comparison to wildtype (wt) without affecting apoptosis. The impaired proliferative behavior of c-REL-/- cells was accompanied by a strongly decreased amount of the H2B protein as well as a significant delay in the prometaphase of mitosis compared to c-REL+/+ HeLa Kyoto cells. c-REL-/- cells further showed significantly decreased expression levels of c-REL target genes in comparison to wt. In accordance to our proliferation data, we observed the c-REL knockout to result in a significantly increased resistance against the chemotherapeutic agents 5-Fluoro-2'-deoxyuridine (5-FUDR) and cisplatin. In summary, our findings emphasize the importance of c-REL signaling in a cellular model of cervical cancer with direct clinical implications for the development of new treatment strategies.
Published: 2017
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3. Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers

Author: Elena Henkel, Markolf Hanefeld, Stefan R. Bornstein, Bernhard Schipp, Jan Sradnick, Frank Pistrosch, Andreas L. Birkenfeld, Dorothea Schipp, Jan B. Matschke, Ingo Weigmann, University of Zurich, and Pistrosch, Frank
Subjects: medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 10265 Clinic for Endocrinology and Diabetology, 610 Medicine & health, Type 2 diabetes, Pulse Wave Analysis, Gastroenterology, Article, Rivaroxaban, Cell-Derived Microparticles, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Platelet, Prospective Studies, Platelet activation, Endothelial dysfunction, Pulse wave velocity, Aspirin, business.industry, Platelet Activation, medicine.disease, 2712 Endocrinology, Diabetes and Metabolism, Diabetes Mellitus, Type 2, 2724 Internal Medicine, Cardiovascular Diseases, Arterial stiffness, Drug Therapy, Combination, business, Biomarkers, Platelet Aggregation Inhibitors, medicine.drug
Abstract: Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract
Published: 2021
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4. Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial

Author: Oliver Kuss, Konstantinos Kantartzis, Christian Herder, Michael Roden, Birgit Knebel, Andreas Pfeiffer, Stefan Kabisch, Martin Wolkersdorfer, Elena Henkel, Jong-Hee Hwang, Jürgen Machann, Stefan Kopf, Christian Kasperk, Norbert Stefan, Stefan R. Bornstein, Sofiya Gancheva, Hisayuki Katsuyama, Merit Lagerpusch, Sabine Kahl, Daniel F. Markgraf, Klaus Straßburger, Andreas L. Birkenfeld, Yuliya Kupriyanova, Theresa van Gemert, University of Zurich, and Roden, Michael
Subjects: Blood Glucose, Male, medicine.medical_specialty, 2902 Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, 10265 Clinic for Endocrinology and Diabetology, Urology, Down-Regulation, 610 Medicine & health, 030209 endocrinology & metabolism, Type 2 diabetes, Placebos, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Double-Blind Method, Glucosides, Non-alcoholic Fatty Liver Disease, Germany, Diabetes mellitus, Weight Loss, Nonalcoholic fatty liver disease, Internal Medicine, Empagliflozin, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Benzhydryl Compounds, Adiposity, Aged, Advanced and Specialized Nursing, Adiponectin, business.industry, Middle Aged, medicine.disease, 2712 Endocrinology, Diabetes and Metabolism, Adipose Tissue, Diabetes Mellitus, Type 2, Liver, chemistry, 2724 Internal Medicine, Female, Liver function, Insulin Resistance, business, EMPA
Abstract: OBJECTIVE To evaluate whether the sodium–glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (LFC) in recent-onset and metabolically well-controlled type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS Patients with T2D (n = 84) (HbA1c 6.6 ± 0.5% [49 ± 10 mmol/mol], known disease duration 39 ± 27 months) were randomly assigned to 24 weeks of treatment with 25 mg daily EMPA or placebo. The primary end point was the difference of the change in LFC as measured with magnetic resonance methods from 0 (baseline) to 24 weeks between groups. Tissue-specific insulin sensitivity (secondary outcome) was assessed by two-step clamps using an isotope dilution technique. Exploratory analysis comprised circulating surrogate markers of insulin sensitivity and liver function. Statistical comparison was done by ANCOVA adjusted for respective baseline values, age, sex, and BMI. RESULTS EMPA treatment resulted in a placebo-corrected absolute change of −1.8% (95% CI −3.4, −0.2; P = 0.02) and relative change in LFC of −22% (−36, −7; P = 0.009) from baseline to end of treatment, corresponding to a 2.3-fold greater reduction. Weight loss occurred only with EMPA (placebo-corrected change −2.5 kg [−3.7, −1.4]; P < 0.001), while no placebo-corrected change in tissue-specific insulin sensitivity was observed. EMPA treatment also led to placebo-corrected changes in uric acid (−74 mol/L [−108, −42]; P < 0.001) and high-molecular-weight adiponectin (36% [16, 60]; P < 0.001) levels from 0 to 24 weeks. CONCLUSIONS EMPA effectively reduces hepatic fat in patients with T2D with excellent glycemic control and short known disease duration. Interestingly, EMPA also decreases circulating uric acid and raises adiponectin levels despite unchanged insulin sensitivity. EMPA could therefore contribute to the early treatment of nonalcoholic fatty liver disease in T2D.
Published: 2019
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5. Hypoglycemia is associated with acute changes in the QTc interval and reduced heart rate in type 2 diabetic patients with cardiovascular disease in a real world setting

Author: Markolf Hanefeld, F Pistrosch, P Gardemann, Andreas L. Birkenfeld, and Elena Henkel
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Heart rate, medicine, Cardiology, Disease, Hypoglycemia, business, medicine.disease, QT interval
Published: 2017
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6. 133-OR: Effects of Empagliflozin on Liver Fat Content in Type 2 Diabetes: The EMLIFA001 Trial

Author: Christian Kasperk, Jürgen Machann, Klaus Strassburger, Yuliya Kupriyanova, Hisayuki Katsuyama, Christian Herder, Sofiya Gancheva, Oliver Kuss, Elena Henkel, Andreas L. Birkenfeld, Stefan Kabisch, Norbert Stefan, Konstantinos Kantartzis, Stefan Kopf, Jong-Hee Hwang, Sabine Kahl, Andreas Pfeiffer, and Michael Roden
Subjects: 0301 basic medicine, medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease, Placebo, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Insulin resistance, Diabetes mellitus, Internal medicine, Nonalcoholic fatty liver disease, Liver fat, Internal Medicine, medicine, Empagliflozin, business, Body mass index
Abstract: Type 2 diabetes (T2D) associates with nonalcoholic fatty liver disease (NAFLD), which itself contributes to both insulin resistance and excessive cardiovascular risk of diabetes. Nevertheless, there is currently no established therapy for NAFLD in T2D. This trial examined whether treatment with the sodium glucose transporter 2 inhibitor empagliflozin (EMPA) reduces liver fat content (HCL, primary outcome) in metabolically well-controlled patients with short known disease duration. T2D patients (n=84; 63±8 years; body mass index (BMI) 32.2±4.5 kg/m2, HbA1c 6.6±0.5%, disease duration 38±27 months) were randomly assigned to 24-week treatment with either EMPA 25 mg per day or placebo (PLAC). HCL was measured by 1H-magnetic resonance (MR) spectroscopy (STEAM) and fat-selective MR imaging (IDEAL). Statistical analysis was done by ANCOVA adjusted for the respective baseline value, age, sex and BMI. After treatment, HCL was reduced compared to baseline (relative change (RC) EMPA -33%[95% confidence interval -43;-23], p In conclusion, empagliflozin effectively reduces HCL in well-controlled T2D patients and increases serum adiponectin with beneficial effects on hepatocellular integrity. Thus, empagliflozin may improve NAFLD via distinct different mechanisms. Disclosure S. Kahl: None. S. Gancheva: None. K. Strassburger: None. C. Herder: None. J. Machann: None. H. Katsuyama: None. S. Kabisch: Research Support; Self; California Walnut Commission, Institute for Grain Processing, Nuthetal, J. Rettenmaier Söhne, Südzucker / Beneo. Other Relationship; Self; Berlin-Chemie AG, Sanofi. E. Henkel: None. S. Kopf: None. K. Kantartzis: None. Y. Kupriyanova: None. O. Kuss: None. J. Hwang: None. C. Kasperk: None. N. Stefan: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Sanofi. A.F. Pfeiffer: Advisory Panel; Self; Abbott, Berlin-Chemie AG, Novo Nordisk A/S. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG, Sanofi-Aventis Deutschland GmbH. A.L. Birkenfeld: None. M. Roden: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Poxel SA, Servier. Board Member; Self; Eli Lilly and Company. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi. Speaker's Bureau; Self; Novo Nordisk Inc. Funding Boehringer Ingelheim Pharma GmbH
Published: 2019
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7. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

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

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

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

9. Efficacy and safety of once-Weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-Week, open-Label, randomized clinical trial

Author: Vanita R. Aroda, Guillaume Charpentier, Miriam Annett, Matthew Capehorn, Andrew J. Ahmann, Anders G. Holst, Elena Henkel, Ildiko Lingvay, and Francesco Dotta
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Glucagon-Like Peptides, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, Drug Administration Schedule, law.invention, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Endocrinology, Randomized controlled trial, law, Diabetes mellitus, Internal medicine, Internal Medicine, Advanced and Specialized Nursing, Clinical endpoint, Medicine, Humans, Hypoglycemic Agents, Glycemic, Aged, Aged, 80 and over, Glycated Hemoglobin, business.industry, Venoms, Semaglutide, Body Weight, Middle Aged, medicine.disease, Metformin, Clinical trial, Diabetes and Metabolism, Treatment Outcome, Diabetes Mellitus, Type 2, Delayed-Action Preparations, Exenatide, Female, business, Peptides, medicine.drug
Abstract: OBJECTIVE To compare the efficacy and safety of once-weekly semaglutide 1.0 mg s.c. with exenatide extended release (ER) 2.0 mg s.c. in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS In this phase 3a, open-label, parallel-group, randomized controlled trial, 813 subjects with type 2 diabetes taking oral antidiabetic drugs were randomized (1:1) to semaglutide 1.0 mg or exenatide ER 2.0 mg for 56 weeks. The primary end point was change from baseline in HbA1c at week 56. RESULTS Mean HbA1c (8.3% [67.7 mmol/mol] at baseline) was reduced by 1.5% (16.8 mmol/mol) with semaglutide and 0.9% (10.0 mmol/mol) with exenatide ER (estimated treatment difference vs. exenatide ER [ETD] –0.62% [95% CI –0.80, –0.44] [–6.78 mmol/mol (95% CI –8.70, –4.86)]; P < 0.0001 for noninferiority and superiority). Mean body weight (95.8 kg at baseline) was reduced by 5.6 kg with semaglutide and 1.9 kg with exenatide ER (ETD –3.78 kg [95% CI –4.58, –2.98]; P < 0.0001). Significantly more subjects treated with semaglutide (67%) achieved HbA1c CONCLUSIONS Semaglutide 1.0 mg was superior to exenatide ER 2.0 mg in improving glycemic control and reducing body weight after 56 weeks of treatment; the drugs had comparable safety profiles. These results indicate that semaglutide treatment is highly effective for subjects with type 2 diabetes who are inadequately controlled on oral antidiabetic drugs.
Published: 2018

10. IKK1/2 protect human cells from TNF-mediated RIPK1-dependent apoptosis in an NF-κB-independent manner

Author: Christian Kaltschmidt, Carsten Slotta, Barbara Kaltschmidt, Johannes F. W. Greiner, Nina Pfisterer, Svenja Kleinwächter, Lucia M. Ruiz-Perera, Elena Henkel, Jonathan Storm, and Maren Pieper
Subjects: 0301 basic medicine, Cell death, Programmed cell death, RIPK1, Tumor necrosis factor, Apoptosis, IκB kinase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Annexin, Humans, Molecular Biology, poptosis, IKK, Tumor Necrosis Factor-alpha, NF-kappa B, NF-κB, Cell Biology, NFKB1, I-kappa B Kinase, 030104 developmental biology, NF-kappa-B, HEK293 Cells, chemistry, 030220 oncology & carcinogenesis, Receptor-Interacting Protein Serine-Threonine Kinases, Cancer research, Tumor necrosis factor alpha, CRISPR-Cas Systems, Signal Transduction
Abstract: TNF signaling is directly linked to cancer development and progression. A broad range of tumor cells is able to evade cell death induced by TNF impairing the potential anti-cancer value of TNF in therapy. Although sensitizing cells to TNF-induced death therefore has great clinical implications, detailed mechanistic insights into TNF-mediated human cell death still remain unknown. Here, we analyzed human cells by applying CRISPR/Cas9n to generate cells deficient of IKK1, IKK2, IKK1/2 and RELA. Despite stimulation with TNF resulted in impaired NF-κB activation in all genotypes compared to wildtype cells, increased cell death was observable only in IKK1/2-double-deficient cells. Cell death could be detected by Caspase-3 activation and binding of Annexin V. TNF-induced programmed cell death in IKK1/2-/- cells was further shown to be mediated via RIPK1 in a predominantly apoptotic manner. Our findings demonstrate the IKK complex to protect from TNF-induced cell death in human cells independently to NF-κB RelA suggesting IKK1/2 to be highly promising targets for cancer therapy.
Published: 2017

11. Physical Activity is Strongly Inversely Related To Post-Challenge Plasma Glucose and Glycemic Spikes in a Risk Population for Type 2 Diabetes

Author: Markolf Hanefeld, Elena Henkel, Tsvetan Stefanov, Carsta Koehler, Frank Schaper, and Theodora Temelkova-Kurktschiev
Subjects: Adult, Blood Glucose, Male, Risk, medicine.medical_specialty, medicine.medical_treatment, Population, Type 2 diabetes, Body Mass Index, Impaired glucose tolerance, Internal medicine, Diabetes mellitus, medicine, Humans, education, Exercise, Aged, Glycemic, education.field_of_study, Univariate analysis, business.industry, Insulin, General Medicine, Glucose Tolerance Test, Middle Aged, medicine.disease, Endocrinology, Diabetes Mellitus, Type 2, Female, business, Body mass index
Abstract: AIM: To examine the relationship between physical activity (PA) and various cardiometabolic risk factors during an oral glucose tolerance test (OGTT), including glycemic spikes (PGS) in individuals at risk for type 2 diabetes. SUBJECTS AND METHODS: A total of 949 middle-aged subjects from the Risk factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) trial aged 40-70 years were included in the present cross-sectional analysis. Standard 75 g OGTT was performed and blood was collected every 30 min for 2 hours for measurements of plasma glucose (PG) and other cardiometabolic risk factors. PA was assessed using interviewer-administered questionnaire. RESULTS: Post-challenge PGS and maximal PG (PGmax) during OGTT were significantly lower in individuals with high PA vs. individuals with low PA even after body mass index (BMI) adjustment (p = 0.026 and p = 0.035, respectively). In univariate analysis post-challenge PG 30, 60, 90, and 120 minutes, PGS and PGmax during OGTT were significantly inversely correlated to PA. This correlation was attenuated but remained significant after adjustment for BMI. Fasting PG and glycosylated hemoglobin were not correlated to PA. Significantly higher fasting and post-challenge insulin levels were found among subjects with low vs. subjects with medium (p < 0.05) and high PA (p < 0.05). Post-challenge C-peptide and proinsulin levels were significantly lower in participants with high vs. participants with low PA (p < 0.05 for all). The relationship between 2-h PG and PA was observed also in lean subjects and in subjects with normal fasting glucose. In multivariate analysis PA was a significant independent determinant of 2-h PG. CONCLUSION: We found a strong inverse relationship between PA and various post-challenge cardiometabolic parameters during OGTT, including glycemic spikes, in a population at risk for diabetes. This relationship was only partially dependent on BMI.
Published: 2013
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12. Einfluss der Qualität der Diabeteskontrolle auf systematische Vascular Endothelial Growth Factors (VEGF) und Biomarker der subklinischen Inflammation bei Typ 2 Diabetes

Author: Andreas L. Birkenfeld, Markolf Hanefeld, Stefan R. Bornstein, X Ganz, D Sandner, Elena Henkel, Rocco Haase, D Appelt, and K Engelmann
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2016
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13. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial

Author: Dick, de Zeeuw, Pirow, Bekker, Elena, Henkel, Christopher, Hasslacher, Ioanna, Gouni-Berthold, Heidrun, Mehling, Antonia, Potarca, Vladimir, Tesar, Hiddo J Lambers, Heerspink, Thomas J, Schall, A, Woodman, Groningen Kidney Center (GKC), Methods in Medicines evaluation & Outcomes research (M2O), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, medicine.medical_specialty, Receptors, CCR2, Endocrinology, Diabetes and Metabolism, Population, Renal function, Type 2 diabetes, Placebo, law.invention, chemistry.chemical_compound, Endocrinology, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Internal Medicine, Clinical endpoint, Medicine, Albuminuria, Humans, Diabetic Nephropathies, education, Aged, Creatinine, education.field_of_study, Sulfonamides, INSULIN-RESISTANCE, business.industry, MONOCYTE CHEMOATTRACTANT PROTEIN-1, Middle Aged, medicine.disease, Surgery, REDUCTION, MICE, TARGET, chemistry, Diabetes Mellitus, Type 2, Chemotherapy, Adjuvant, OBESITY, Female, medicine.symptom, business
Abstract: Summary Background Patients with type 2 diabetes and nephropathy have high cardiorenal morbidity and mortality despite optimum treatment including angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Residual risk is related to residual albuminuria. We assessed whether CCX140-B, a selective inhibitor of C-C chemokine receptor type 2 (CCR2), could further reduce albuminuria when given in addition to standard care, including ACE inhibitors or ARBs. Methods In this randomised, double-blind, placebo-controlled clinical trial, we recruited patients from 78 research centres in Belgium, Czech Republic, Germany, Hungary, Poland, and the UK. We enrolled patients with type 2 diabetes aged 18–75 years with proteinuria (first morning void urinary albumin to creatinine ratio [U ACR ] 100–3000 mg/g), estimated glomerular filtration rate of 25 mL/min per 1·73 m 2 or higher, and taking stable antidiabetic treatment and ACE inhibitors or ARBs, for at least 8 weeks before study entry. Patients were stratified based on baseline U ACR and renal function (estimated glomerular filtration rate), and then randomly assigned (1:1:1) via an interactive web response system with a minimisation algorithm to oral placebo, 5 mg CCX140-B, or 10 mg CCX140-B once a day. The 12-week dosing period in the initial protocol was extended to 52 weeks by protocol amendment. The primary efficacy measure was change from baseline in U ACR during 52 weeks in the modified intention-to-treat population (all patients with uninterrupted dosing, excluding patients who stopped dosing at week 12 either permanently under the original protocol, or temporarily because of delay in approval of the protocol amendment). We did safety analyses on all randomly assigned patients who received at least one dose of study drug. According to a prespecified analysis plan, we analysed the primary endpoint with one-sided statistical testing with calculation of upper 95% confidence limits of the differences between active and control. This trial is registered with ClinicalTrials.gov, number NCT01447147. Findings The study ran from Dec 7, 2011 (first patient enrolled), until Aug 4, 2014. We enrolled 332 patients: 111 were assigned to receive placebo, 110 to 5 mg CCX140-B, and 111 to 10 mg CCX140-B. Of these, 192 were included in the modified intention-to-treat population. U ACR changes from baseline during 52 weeks were −2% for placebo (95% CI −11% to 9%), −18% for 5 mg CCX140-B (−26% to −8%), and −11% for 10 mg CCX140-B (−20% to −1%). We recorded a −16% difference between 5 mg CCX140-B and placebo (one-sided upper 95% confidence limit −5%; p=0·01) and a −10% difference between 10 mg CCX140-B and placebo (upper 95% confidence limit 2%; p=0·08). Adverse events occurred in 81 (73%) of 111 patients in the placebo group versus 71 (65%) of 110 patients in the CCX140-B 5 mg group and 68 (61%) of 111 patients in the CCX140-B 10 mg group; there were no renal events during the study. Interpretation Our data suggest that CCR2 inhibition with CCX140-B has renoprotective effects on top of current standard of care in patients with type 2 diabetes and nephropathy. Funding ChemoCentryx.
Published: 2015

14. Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus

Author: Markolf Hanefeld, Mario Menschikowski, Carsta Koehler, Elena Henkel, and W. Leonhardt
Subjects: Adult, Blood Glucose, Male, endocrine system, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Glucagon, Impaired glucose tolerance, Endocrinology, Insulin resistance, Internal medicine, Glucose Intolerance, medicine, Humans, Insulin, Pancreatic hormone, Aged, Glucose tolerance test, medicine.diagnostic_test, business.industry, digestive, oral, and skin physiology, Glucagon secretion, nutritional and metabolic diseases, Fasting, Glucose Tolerance Test, Middle Aged, Postprandial Period, medicine.disease, Dietary Fats, Postprandial, Diabetes Mellitus, Type 2, Hyperglycemia, Multivariate Analysis, Dietary Proteins, business, hormones, hormone substitutes, and hormone antagonists
Abstract: Glucagon is the physiological antagonist of insulin. Postprandial (pp) hyperglycemia in impaired glucose tolerance (IGT) and in type 2 diabetes mellitus (T2DM) may also depend on irregularities in glucagon secretion. This study investigated the glucagon excursion after a lipid-glucose-protein tolerance test in subjects with different stages of glucose intolerance. We also analyzed the relationship between pp glucagon secretion and hyperglycemias. A total of 64 men (27 healthy subjects with normal glucose tolerance [NGT], 15 with IGT, and 22 with T2DM) were examined. Plasma glucose (PG), insulin, proinsulin, free fatty acids, and triglycerides were measured in the fasting state and at 30 minutes and 2, 3, 4, and 6 hours after the intake of the test meal, which contained 126 g carbohydrates, 92 g fat, and 17 g protein. Postprandial concentrations of metabolic parameters were calculated as area under the curve (AUC). Glucagon was measured in the fasting state and at 30 minutes and 2 and 4 hours pp. Early glucagon increment was defined as glucagon at 30 minutes minus fasting glucagon. The insulin response was quantified as insulin increment divided by PG increment in the corresponding time. Insulin resistance was calculated using lomeostasis model assessment (HOMA). Fasting glucagon was significantly increased in IGT vs NGT (P
Published: 2005
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15. Acarbose Slows Progression of Intima-Media Thickness of the Carotid Arteries in Subjects With Impaired Glucose Tolerance

Author: Carsta Koehler, Markolf Hanefeld, Jean Louis Chiasson, Frank Schaper, Theodora Temelkova-Kurktschiev, and Elena Henkel
Subjects: Adult, Carotid Artery Diseases, Male, medicine.medical_specialty, Carotid Artery, Common, Subgroup analysis, Placebo, Placebos, Prediabetic State, Impaired glucose tolerance, Internal medicine, Diabetes mellitus, Glucose Intolerance, medicine, Humans, Hypoglycemic Agents, Risk factor, Prospective cohort study, Aged, Ultrasonography, Acarbose, Advanced and Specialized Nursing, business.industry, Middle Aged, medicine.disease, Treatment Outcome, Endocrinology, Diabetes Mellitus, Type 2, Intima-media thickness, Disease Progression, Cardiology, Female, Neurology (clinical), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Tunica Intima, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies, medicine.drug
Abstract: Background and Purpose— Impaired glucose tolerance (IGT)–a prediabetic state–is an important risk factor for atherosclerosis. Acarbose, an α-glucosidase inhibitor, was shown in the placebo-controlled prospective study to prevent noninsulin-dependent diabetes mellitus (STOP-NIDDM) trial to reduce the risk of diabetes by 36% in IGT subjects. This article reports on a placebo-controlled subgroup analysis of the STOP-NIDDM study to examine the efficacy of acarbose to slow progression of intima-media thickness (IMT) in subjects with IGT. Methods— One hundred thirty-two IGT subjects were randomized to placebo (n=66) or acarbose (n=66) 100 mg 3 times daily; the study duration was at least 3 years, mean follow-up time 3.9 (SD 0.6) years. Carotid IMT was determined at study entry and the end of the trial. The intent-to-treat analysis included 56 subjects in the acarbose and 59 in the control group who had a baseline and endpoint measurement. Results— A significant reduction of the progression of IMT mean was observed in the acarbose group versus placebo. After an average time of 3.9 years, IMT mean increased by 0.02 (0.07) mm in the acarbose group versus 0.05 (0.06) mm in the placebo group ( P =0.027). The annual increase of IMT mean was reduced by ≈50% in the acarbose group versus placebo. Multiple linear regression revealed IMT progression as significantly related to acarbose intake. Conclusions— Acarbose slows progression of IMT in IGT subjects, a high-risk population for diabetes and atherosclerosis. This is the first placebo-controlled prospective subgroup analysis, demonstrating that counterbalancing of postprandial hyperglycemia may be vasoprotective.
Published: 2004
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16. Insulin Secretion and Insulin Sensitivity Pattern Is Different in Isolated Impaired Glucose Tolerance and Impaired Fasting Glucose

Author: Carsta Koehler, Frank Schaper, Theodora Temelkova-Kurktschiev, Katja Fuecker, Markolf Hanefeld, and Elena Henkel
Subjects: Advanced and Specialized Nursing, medicine.medical_specialty, Glucose tolerance test, endocrine system diseases, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, nutritional and metabolic diseases, Type 2 diabetes, medicine.disease, Impaired fasting glucose, Impaired glucose tolerance, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, business, Proinsulin
Abstract: OBJECTIVE—Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance. RESEARCH DESIGN AND METHODS—This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories. RESULTS—All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance. CONCLUSIONS—Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.
Published: 2003
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17. Coagulation factor V G allele and HR2 haplotype

Author: Heike, Kostka, Thomas, Schwarz, Sebastian, Schellong, Cornelia, Mix, Eberhard, Kuhlisch, Theodora, Temelkova-Kurktschiev, Elena, Henkel, Carsta, Köhler, Siegmund, Gehrisch, and Gabriele, Siegert
Subjects: Adult, Aged, 80 and over, Male, Venous Thrombosis, Guanine, Adolescent, Factor V, Hematology, General Medicine, Middle Aged, Polymorphism, Single Nucleotide, Gene Frequency, Haplotypes, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Alleles, Activated Protein C Resistance, Aged
Abstract: Factor V Leiden is a well-known risk factor for venous thrombosis. The dual role of factor V as a coagulatory and anticoagulatory cofactor permits the assumption that further mutations in the factor V gene are of importance in the study of the risk of thrombosis. Relevant studies to date have given rise to a controversy over this risk for the HR2 haplotype. For the G allele, defined in our work group as a G at the nucleotide positions 2391, 2663, 2684 and 2863, there have been to date no other investigations of thrombotic risk. In a case-control study on 347 patients with deep venous thrombosis (DVT) and 282 controls, we investigated the association of the HR2 haplotype and the G allele with DVT. We found no association between HR2 haplotype and DVT [odds ratio (OR) 0.87; 95% confidence interval (CI) 0.58-1.30; P = 0.537]. The frequency of the G allele was, on the contrary, higher in the control group than among the patients (OR 0.68, 95% CI: 0.53 to 0.89; P = 0.005). The factor V activity of the HR2 carriers was lower than that of the wild type and G allele carriers. The HR2 haplotype exhibited a moderate influence on activated protein C response. This study presented no evidence of thrombotic risk for the HR2 haplotype alone. The results here permit the assumption of a protective effect of the G allele. The source of a possible protective influence of the G allele on thrombotic risk is at present unclear.
Published: 2003
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18. Leukocyte count and fibrinogen are associated with carotid and femoral intima-media thickness in a risk population for diabetes

Author: Carsta Koehler, Elena Henkel, Markolf Hanefeld, and Theodora Temelkova-Kurktschiev
Subjects: Adult, Male, medicine.medical_specialty, Arteriosclerosis, Carotid Artery, Common, Physiology, Population, Type 2 diabetes, Fibrinogen, Impaired glucose tolerance, Leukocyte Count, Risk Factors, Physiology (medical), Internal medicine, Diabetes mellitus, medicine, Humans, Risk factor, education, Aged, Analysis of Variance, education.field_of_study, business.industry, Middle Aged, medicine.disease, Femoral Artery, Endocrinology, Diabetes Mellitus, Type 2, Intima-media thickness, Multivariate Analysis, Female, Metabolic syndrome, Tunica Intima, Tunica Media, Cardiology and Cardiovascular Medicine, business, Diabetic Angiopathies, medicine.drug
Abstract: Objective: To investigate the relationship of the inflammatory parameters—leukocyte count and fibrinogen level—to the intima-media thickness (IMT) of the common carotid artery and the common femoral artery, as well as to a variety of risk factors within the metabolic syndrome in a risk population for diabetes. Methods: A total of 597 subjects were analyzed from the Risk factors in Impaired glucose tolerance for Atherosclerosis and Diabetes (RIAD) study, who were at risk for the development of type 2 diabetes. IMT of the common carotid and common femoral artery was determined by B-mode ultrasound. Leukocyte count and fibrinogen level, as well as various risk factors for atherosclerosis, were measured by established methods. Results: In univariate analysis, leukocyte count and fibrinogen level correlated significantly to carotid and femoral IMT. Leukocyte count was significantly correlated to body mass index, waist to hip ratio, blood pressure, plasma triglycerides, high-density lipoprotein cholesterol (inversely), fasting and postprandial plasma glucose, insulin and proinsulin, PAI(active), tPA and microalbuminuria, as well as to smoking and physical activity (inversely). Fibrinogen level was significantly correlated with body mass index, systolic blood pressure, plasma triglycerides, fasting plasma glucose, HbA1c, PAI(active), tPA and von Willebrandt factor, as well as with smoking and low physical activity. In multivariate analysis, leukocyte count was an independent determinant of the maximal carotid IMT and fibrinogen level of femoral IMT. Conclusions: Our study indicates that low-grade inflammation is correlated to IMT, as an indicator of early atherosclerosis, and is strongly associated to a variety of risk factors within the metabolic syndrome in a population at risk for type 2 diabetes.
Published: 2002
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19. Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes

Author: S. Bergmann, G. Siegert, W. Jaro, Carsta Koehler, Theodora Temelkova-Kurktschiev, Markolf Hanefeld, and Elena Henkel
Subjects: Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, Blood Pressure, Type 2 diabetes, Body Mass Index, Impaired glucose tolerance, Leukocyte Count, Endocrinology, Insulin resistance, Risk Factors, Internal medicine, Diabetes mellitus, Insulin Secretion, medicine, Humans, Insulin, education, Glycated Hemoglobin, Inflammation, Metabolic Syndrome, education.field_of_study, biology, business.industry, C-reactive protein, Fibrinogen, Glucose Tolerance Test, Middle Aged, medicine.disease, Causality, C-Reactive Protein, Diabetes Mellitus, Type 2, Multivariate Analysis, biology.protein, Body Constitution, Female, Insulin Resistance, Metabolic syndrome, business, Follow-Up Studies
Abstract: Subclinical inflammation was shown to be a strong predictor of cardiovascular events and was suggested to be a part of the metabolic syndrome (MS). The aim of the present study was to investigate the relationship of the inflammatory parameters[mdash ]leukocyte count, C-reactive protein (CRP), and fibrinogen level[mdash ]to insulin resistance and insulin secretion, as well as to other components of the MS in a population at risk for diabetes. A total of 396 subjects (142 men and 254 women) were analyzed from the follow-up of the Risk Factors in Impaired Glucose tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study, who were at risk for type 2 diabetes, such as family history of diabetes, obesity, and/or hyper/dyslipoproteinemia. Subjects under lipid-lowering treatment or with acute infections were not eligible. A variety of risk factors within the MS were examined: lipids, glycemic parameters, coagulation, insulin fractions. and microalbuminuria. CRP was determined by a highly sensitive method, using an immunological agglutination test, and fibrinogen was measured by the method of Clauss. Insulin resistance was evaluated by the homeostasis model assessment (HOMA) and insulin secretion by HOMA and by insulin areas under curve in an oral glucose tolerance test (OGTT), insulin increment at 30 mnutes of OGTT, and insulin increment/glucose increment at 30 minutes of OGTT. By univariate analysis, fibrinogen level ( r = 0.180, P [lt ] .001), leukocyte count ( r = 0.162, P = .001), and CRP ( r = 0.251, P [lt ] .001) were all highly significantly correlated to insulin resistance, but not to insulin secretion. A significant rise was found for the majority of the components of the MS in quartiles of the examined inflammatory parameters. In multivariate analysis of all analyzed metabolic parameters, including age, sex, physical activity, and smoking, body mass index (BMI) was found a strong independent determinant of all inflammatory markers examined. Thus, in a population at risk for type 2 diabetes we demonstrate that subclinical inflammation underlies the metabolic syndrome, through association to one of its primary anomalies[mdash ]insulin resistance, whereas no association was found to impaired insulin secretion.
Published: 2002
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20. Prädiktoren von Glukosetoleranzstörungen in einer Risikopopulation für Typ-2-Diabetes: die RIAD-Studie

Author: C Köhler, Theodora Temelkova-Kurktschiev, Markolf Hanefeld, and Elena Henkel
Subjects: medicine.medical_specialty, endocrine system diseases, business.industry, Insulin, medicine.medical_treatment, nutritional and metabolic diseases, General Medicine, Type 2 diabetes, medicine.disease, Impaired glucose tolerance, Insulin resistance, Endocrinology, Basal (medicine), Internal medicine, Diabetes mellitus, medicine, Metabolic syndrome, business, hormones, hormone substitutes, and hormone antagonists, Proinsulin
Abstract: BACKGROUND AND OBJECTIVE Early detection of glucose intolerance is an important issue in diabetes care. In the metabolic syndrome it is associated with an increased incidence of cardiovascular events. So far it is not clear which anthropometric and metabolic/hormonal parameters are of importance in the conversion of normal to impaired glucose tolerance. PATIENTS AND METHODS The participants of the RIAD (Risk factors in IGT for Atherosclerosis and Diabetes) study had to meet the following criteria: related to type 2 diabetic patients, obesity and/or dyslipidaemia. A total of 358 subjects (age: 40-70 years) with normal glucose tolerance (NGT) in an oral glucose tolerance test (OGTT, 75 g glucose), were examined after a follow-up of 2.90 +/- 0.47 years. 284 of them remained with normal glucose tolerance, while 64 developed an impaired glucose tolerance (IGT) and ten type 2 diabetes (T2DM). The data of the initial screening examination were analysed in three groups (NGT-NGT; NGT-IGT; NGT-T2DM). Plasma glucose (PG), insulin, C-peptide and proinsulin were measured in the fasting state, as well as every 30 minutes during an OGTT, and also basal plasminogen activator inhibitor (PAI) and inflammatory parameters. RESULTS Subjects who converted to IGT or diabetes show, already in the stage of normal glucose tolerance, clear tendency for the development of the metabolic syndrome. They were more obese and had higher fasting and 2 hPG values. The early phase insulin secretion, calculated as a ratio of DeltaInsulin 30'/DeltaPG 30', was lower in the IGT and the diabetes groups (n. s.). Both groups showed a significantly increased insulin resistance. Both converter groups revealed significantly higher PAI (Plasminogen-Activator-Inhibitor) levels and a striking but not significant increase in inflammatory parameters. CONCLUSIONS Subjects who develop IGT and type 2 diabetes, will already in the stage of NGT show an impairment of insulin secretion and higher insulin resistance. Both processes seem to develop parallel to each other and determine the progress of the glucose intolerance. Fasting and 2h post-challenge glucose were the most important predictors of subsequent glucose intolerance.
Published: 2002
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21. Étude SUSTAIN 3 : efficacité et tolérance du semaglutide une fois par semaine versus exanatide-LP après 56 semaines chez des diabétiques de type 2

Author: Guillaume Charpentier, Anders G. Holst, Miriam Annett, Andrew J. Ahmann, Ildiko Lingvay, Vanita R. Aroda, Francesco Dotta, Matthew Capehorn, A. Bouzidi, and Elena Henkel
Subjects: Endocrinology, Endocrinology, Diabetes and Metabolism, Internal Medicine, General Medicine
Published: 2017
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22. Correlation between VEGF-A, biomarker of inflammation and dysglycemia

Author: F Pistrosch, D Appelt, C Köhler, D Sandner, Elena Henkel, Markolf Hanefeld, X Ganz, and K Engelmann
Subjects: biology, business.industry, Endocrinology, Diabetes and Metabolism, VEGF receptors, Inflammation, General Medicine, Endocrinology, Immunology, Internal Medicine, biology.protein, Cancer research, Medicine, Biomarker (medicine), medicine.symptom, business
Published: 2014
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23. Intima-Media-Dicke bei Gesunden ohne Risikofaktorenfür Arteriosklerose

Author: Sabine Fischer, Theodora Temelkova-Kurktschiev, C. Koehler, G. Mennicken, Elena Henkel, and Markolf Hanefeld
Subjects: medicine.medical_specialty, business.industry, General Medicine, Arteriosclerosis, medicine.disease, Arterial occlusion, Postprandial, Intima-media thickness, medicine.artery, Internal medicine, Diabetes mellitus, cardiovascular system, Albuminuria, medicine, Cardiology, cardiovascular diseases, Common carotid artery, medicine.symptom, business, Stroke
Abstract: Background and objective Ultrasound examination of the intima-media thickness (IMT) is a well accepted, highly reproducible method for the evaluation of early atherosclerosis. However, for the exact interpretation of these measurements reference values for IMT should be determined. The present work provides for the first time normal values for IMT of the common carotid artery and the arteries of the lower limbs (common femoral, superficial and popliteal arteries) in a German population of healthy subjects without risk factors. Subjects and methods A total of 112 subjects (50 men, 62 women), aged 40 to 70, were examined, according to the following inclusion criteria: no diabetes or marked elevation of postprandial plasma glucose; non-smokers; no hypertension, obesity, dys/hyperlipidaemia or albuminuria; no history of coronary heart disease, stroke and peripheral arterial occlusion. IMT was measured and standardized by the method of Pignoli. Total cholesterol, triglycerides, HDL-cholesterol, HbA1c, plasma glucose (fasting and postprandial) and albuminuria were examined by routine methods. Results The mean values of double measurements bilaterally in the distal part of the common carotid artery in men were 0.79 (0.73 ... 0.84) mm (40-54 years) and 0.87 (0.81 ... 0.93) mm (55-70 years). In women the values were: -0.70 (0.67 ... 0.75) mm and 0.82 (0.75 ... 0.90) mm, resp. In the group aged 40-54 years the men showed significantly higher IMT of all examined vessels in comparison to the women. In the group aged 55-70 years somewhat higher IMT of the common carotid artery and significantly higher IMT of the arteries of the lower extremity were observed in men. In multivariate analysis age was found to be a significant determinant of IMT of all examined vessels. Conclusion Intima-media thickening of the common carotid artery in men aged 40-70 years is to be accepted if a single measurement of IMT exceeds > or = 1 mm. For women, aged 40-54 years, IMT is defined as pathological if one IMT is above 0.85 mm, and for those aged 55-70 years if IMT exceeds 1 mm.
Published: 2001
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24. Post-challenge hyperglycaemia relates more strongly than fasting hyperglycaemia with carotid intima-media thickness: the RIAD Study

Author: Frank Schaper, Theodora Temelkova-Kurktschiev, Elena Henkel, Katja Fuecker, Carsta Koehler, and Markolf Hanefeld
Subjects: medicine.medical_specialty, Glucose tolerance test, endocrine system diseases, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, nutritional and metabolic diseases, Type 2 Diabetes Mellitus, medicine.disease, Gastroenterology, Asymptomatic, Impaired glucose tolerance, Endocrinology, Intima-media thickness, Diabetes mellitus, Internal medicine, Internal Medicine, Medicine, Population study, medicine.symptom, business, Body mass index
Abstract: SUMMARY Aims Only scarce information exists on the distribution and atherosclerosis risk in different types of hyperglycaemia at diabetes detection. This study aimed to analyse the occurrence of isolated fasting (IFH), isolated post-challenge (IPH) and combined hyperglycaemia (FH/PH) among subjects detected to have diabetes and the association of these types of hyperglycaemia with cardiovascular risk factors and carotid intima-media thickness (IMT). Methods A total of 785 middle-aged subjects of the Risk Factors in Impaired Glucose Tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study underwent a 75-g oral glucose tolerance test and examination of various atherosclerosis risk factors. IMT was measured by B-mode ultrasound. Results One hundred and nineteen (15.2%) asymptomatic diabetic subjects were detected: of these, 35.3% with IFH, 26% with IPH and 38.7% with FH/PH. The level of risk factors was higher in diabetic vs. non-diabetic subjects. HbA1c and cardiovascular risk factors were in the same range for IFH and IPH except for active plasminogen activator inhibitor (PAI)-1 which was significantly higher in IFH. A higher risk burden was found in the FH/PH group vs. both IFH and IPH. IMT was as follows: non-diabetic subjects 0.85 ± 0.18 mm, IFH 0.91 ± 0.20 mm, IPH 0.94 ± 0.18 mm, FH/PH 0.98 ± 0.17 mm (P
Published: 2000
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25. Impaired fasting glucose is not a risk factor for atherosclerosis

Author: Elena Henkel, Frank Schaper, Markolf Hanefeld, Theodora Temelkova-Kurktschiev, Carsta Koehler, and Gabriele Siegert
Subjects: Male, medicine.medical_specialty, endocrine system diseases, Arteriosclerosis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Statistics as Topic, Body Mass Index, Impaired glucose tolerance, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, Glucose Intolerance, Internal Medicine, medicine, Homeostasis, Humans, Glucose homeostasis, Proinsulin, Clinical Laboratory Techniques, business.industry, Insulin, nutritional and metabolic diseases, Fasting, Middle Aged, medicine.disease, Impaired fasting glucose, Cross-Sectional Studies, Intima-media thickness, Case-Control Studies, Female, Metabolic syndrome, business, hormones, hormone substitutes, and hormone antagonists
Abstract: To determine a new category of dysfunctional glucose homeostasis - impaired fasting glucose (IFG) - introduced by the American Diabetes Association (ADA) and the World Health Organization (WHO) defining those with abnormal but nondiabetic fasting glucose values and with a possible risk for developing diabetes. It is not known whether IFG is a risk factor for atherosclerosis, as is impaired glucose tolerance (IGT).In this case-control cross-sectional study in which the oral glucose tolerance (75-g OGTT) and the carotid intima-media thickness (IMT) with B mode ultrasound, as a marker of atherosclerosis, were measured, together with HbA1c, lipids, plasminogen activator (PAI), insulin and proinsulin concentrations in blood plasma. Out of 788 subjects of the risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study we found 104 IFG cases that were compared to 104 controls with fasting plasma glucose (FPG)6.1 mmol/l, matched for age, sex and body mass index. Subjects with 2h postprandial (pp) plasma glucoseor = 11.1 mmol/l were excluded. The rest were subdivided into those with 2h plasma glucose7.8 mmol/l (63 pairs, NGT) and those with plasma glucose7.8 mmol/l and11.1 mmol/l (41 pairs, IGT).The case and control groups showed no significant differences in the major risk factors except for waist-to-hip ratio (WHR) which was higher in the IFG with NGT. IFG with NGT exhibited significantly higher levels of HbA1c, true insulin and proinsulin. In IFG with IGT, only HbA1c and proinsulin were significantly increased vs. controls. IMT was in the same range for cases and controls in both subgroups. However, IMT mean and IMTmax were significantly increased in IFG with IGT vs. IFG with NGT (0.95 mm vs. 0.80 mm and 1.10 mm vs. 0.90 mm). Cumulative distribution analysis of IMT illustrates that IMT in IFG with IGT is more shifted to higher artery wall thickness than in IFG with NGT.In our case-control study IFG alone was not related to increased IMT. Only IFG in a combination with IGT exhibited atherosclerotic changes of the carotid arteries. IFG is not analogous to IGT as a risk factor for atherosclerosis.
Published: 1999
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26. Serum and Plasma Levels of Vascular Endothelial Growth Factors in Relation to Quality of Glucose Control, Biomarkers of Inflammation, and Diabetic Nephropathy

Author: Katrin Engelmann, X Ganz, Dieter Appelt, Stefan R. Bornstein, Elena Henkel, Markolf Hanefeld, Andreas L. Birkenfeld, Rocco Haase, and Dirk Sandner
Subjects: 0301 basic medicine, Blood Glucose, Male, Vascular Endothelial Growth Factor A, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Inflammation, Type 2 diabetes, Biochemistry, Diabetic nephropathy, 03 medical and health sciences, Endocrinology, Risk Factors, Diabetes mellitus, Internal medicine, Medicine, Humans, Diabetic Nephropathies, Platelet activation, Endothelial dysfunction, Aged, Demography, Glycated Hemoglobin, biology, business.industry, C-reactive protein, Biochemistry (medical), General Medicine, medicine.disease, Vascular endothelial growth factor A, 030104 developmental biology, C-Reactive Protein, Diabetes Mellitus, Type 2, Case-Control Studies, Hyperglycemia, Microvessels, biology.protein, Linear Models, Female, medicine.symptom, business, Biomarkers
Abstract: Levels of vascular endothelial growth factors (VEGF) are regulated in a complex network of adipokines, glucose control, and low grade inflammation together with activated platelets, leucocytes, and endothelial dysfunction. Increased levels of VEGF are associated with enhanced angiogenesis and impaired repair mechanisms of vascular lesions in endorgans. Little is known about the interaction of systemic VEGF levels with quality of diabetes control, biomarkers of inflammation, and diabetic nephropathy. Moreover, it is unclear, whether serum and plasma VEGF levels are similarly suited to reflect risk associated with VEGF. In this case control study, we analyzed these parameters in serum and plasma of age and sex matched controls without diabetes (n=99) and type 2 diabetes (n=302). Serum VEGF-A was significantly increased in patients with T2DM while plasma levels were in the same range as for controls. Individual levels varied in a wide range. Serum levels were 4.9 times higher in controls and 7.3 times higher in T2DM as compared to plasma levels. T2DM was associated with significantly higher levels of hsCRP, ALAT, and albumin/creatinine ratio. When calculated for tertiles of HbA1c, we observed a highly significant increase from tertile one to the upper tertile for serum VEGF-A but not for plasma VEGF-A. Correlation analysis revealed a significant relationship between VEGF-A, HbA1c, inflammation, and diabetic nephropathy. Our results indicate that increased VEGF-A levels in T2DM significantly depend on quality of HbA1c control. Serum levels of VEGF-A, with a strong contribution of platelet derived VEGF, better reflect the glycemic burden than plasma levels of VEGF-A. Mechanistic studies are needed to explore links to inflammation and diabetic nephropathy.
Published: 2016
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27. Efficacy and Safety of Once-Weekly Semaglutide vs. Exenatide ER after 56 Weeks in Subjects with Type 2 Diabetes (SUSTAIN 3)

Author: Miriam Annett, Andrew J. Ahmann, Anders G. Holst, Matthew Capehorn, Guillaume Charpentier, Francesco Dotta, Ildiko Lingvay, Elena Henkel, and Vanita R. Aroda
Subjects: medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, Semaglutide, Once weekly, 030209 endocrinology & metabolism, General Medicine, Type 2 diabetes, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, 030212 general & internal medicine, business, Exenatide, medicine.drug
Published: 2016
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28. Association of physical activity with insulin resistance, subclinical inflammation, coagulation, and fibrinolytic biomarkers among population at high risk for type 2 diabetes

Author: Frank Schaper, Markolf Hanefeld, Elena Henkel, Theodora Temelkova-Kurktschiev, Tsvetan Stefanov, and Carsta Koehler
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Population, Type 2 diabetes, Motor Activity, Fibrinogen, Impaired glucose tolerance, Leukocyte Count, Insulin resistance, Risk Factors, Internal medicine, Diabetes mellitus, Fibrinolysis, Plasminogen Activator Inhibitor 1, von Willebrand Factor, medicine, Humans, education, education.field_of_study, Analysis of Variance, Chi-Square Distribution, Anthropometry, business.industry, General Medicine, Middle Aged, medicine.disease, Endocrinology, C-Reactive Protein, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Tissue Plasminogen Activator, Regression Analysis, Female, Insulin Resistance, business, Plasminogen activator, Biomarkers, medicine.drug
Abstract: Objective: To investigate the association of physical activity with insulin resistance and biomarkers of inflammation, coagulation, and fibrinolysis in a population at high risk for type 2 diabetes. Patients and Methods: A total of 778 subjects from the Risk factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study aged 40-70 years were included in the present cross-sectional analysis. Results: Participants classified as having low physical activity (PA) were more insulin resistant in comparison to participants with medium (P = 0.042) and high PA (P = 0.015). Individuals with high physical activity had a significantly lower leucocytes count than individuals with low PA (P = 0.027) and significantly lower hs-CRP and fibrinogen concentrations than individuals with medium (P = 0.011 and P = 0.021) and low physical activity (P = 0.04 and P = 0.007). Although a trend towards a decrease in plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) levels with increasing physical activity was present, significant differences were observed only between subjects with high and medium physical activity (P = 0.045 and P = 0.033). In multivariate regression analyses physical activity was an independent determinant of insulin resistance, leucocytes count, hs-CRP, and fibrinogen concentrations. Conclusions: Physical activity was independently associated with insulin resistance and biomarkers of inflammation, whereas only a tendency towards decreased concentrations of coagulation and fibrinolytic biomarkers with increasing physical activity was observed.
Published: 2012

29. Albuminurie und Typ 2-Diabetesrisiko – Eine prospektive Studie

Author: F Pistrosch, A Heidenreich, Elena Henkel, Stefan R. Bornstein, Frank Schaper, C Köhler, and Markolf Hanefeld
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2010
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30. Evaluierung der Glukosewerte im Tag/Nacht- Profil bei mit Insulin behandelten Patienten mit Typ 2 Diabetes: Ergebnisse einer explorativen Studie mit kontinuierlichem Glukosemonitoring (CGM)

Author: Markolf Hanefeld, C Hoffmann, C Schoner, C Köhler, B Engler, S Bilz, J Stelzer, and Elena Henkel
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2010
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31. Pulse pressure is a strong predictor of cardiovascular risk: Data of the risk factors in impaired glucose tolerance for atherosclerosis and diabetes and the Sofia Metabolic Syndrome studies

Author: Theodora S, Temelkova-Kurktschiev, Dimo P, Kurktschiev, Lyudmila G, Vladimirova-Kitova, Carsta, Koehler, Elena, Henkel, Boryana R, Todorova, Frank, Schaper, Katya, Fuecker, and Markolf, Hanefeld
Subjects: Adult, Blood Glucose, Male, Blood Pressure, Coronary Artery Disease, Glucose Tolerance Test, Middle Aged, Body Mass Index, Carotid Arteries, Diabetes Mellitus, Type 2, Predictive Value of Tests, Risk Factors, Glucose Intolerance, Hypertension, Humans, Female, Obesity, Bulgaria, Aged
Abstract: The aim of the present study was to examine the relationship between pulse pressure (PP), cardiovascular risk factors and intima-media thickness (IMT) in a population at risk for type 2 diabetes and atherosclerosis in Saxony, and to assess the association between PP and history of myocardial infarction in the general population of Bulgaria.The Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study included 1139 subjects, aged 40-70 years, with a family history of type 2 diabetes, obesity and/or hyper/dyslipoproteinemia. The SMS study included 1018 subjects (14 years of age) from the general population of Bulgaria.In RIAD study, PP was significantly correlated with age, plasma glucose, body mass index, microalbuminuria, triglycerides, waist-to-hip ratio, plasminogen activator inhibitor, total cholesterol, free fatty acids, leucocytes count and HDL-cholesterol (inversely). PP was also significantly correlated with carotid IMT. In multivariate analysis PP was an independent determinant of IMT. In the Sofia Metabolic Syndrome (SMS) study PP was significantly correlated with age, body mass index, waist circumference and fasting glucose and was an independent significant determinant of history of myocardial infarction.PP was an important cardiovascular risk factor both in a risk population for type 2 diabetes and atherosclerosis in Saxony and in the general population of Bulgaria.
Published: 2009

32. Beziehungen zwischen latenten nächtlichen Hypoglykämien, Nüchternglukose und postprandialen Glukoseverläufen nach einem standardisierten Frühstück bei insulinpflichtigen Typ 2 Diabetikern ermittelt mittels kontinuierlichem interstitiellen Glukosemonitoring

Author: Wolfgang Landgraf, C Hoffmann, C Köhler, Elena Henkel, S Bilz, C Schoner, and Markolf Hanefeld
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2009
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33. Untersuchung zur retinalen Gefäßfunktion bei gut eingestellten Typ-2-Diabetikern mittels dynamischer retinaler Gefäßanalyse

Author: Tjalf Ziemssen, Markolf Hanefeld, Elena Henkel, J. Stelzer, and H. Hanso
Subjects: Endocrinology, Diabetes and Metabolism
Abstract: Endothelfunktionsstorungen sind fur Typ-2-Diabetes charakteristisch. Ob dies auch fur Diabetiker mit HbA1c im Zielbereich gilt, ist bisher wenig bekannt. Fragestellung: 1. Wir verglichen mittels einer dynamischen retinalen Gefasanalyse die NO-vermittelten Veranderungen der arteriellen und venosen Gefasdurchmesser (eine funktionelle Darstellung der retinalen Durchblutung) bei Patienten mit gut eingestelltem Typ-2-Diabetes und Stoffwechselgesunden 2. Die Beziehungen zwischen quantifizierter Gefasantwort und Diabeteseinstellung und etablierten kardiovaskularen Risikofaktoren wurden analysiert. Methodik: An dieser Case-Control Studie nahmen 20 Typ-2-Diabetiker und 16 Personen mit normaler Glucosetoleranz teil. Maximale arterielle und venose Gefasdilatationen der Retina wurden durch einen Flickerlichtreiz im Rahmen einer direkten, nicht-invasiven und leicht praktikablen Untersuchung mittels Retinal Vessel Analyser (RVA) gemessen. Ein arterio-venoser alterskorrigierter Quotient (AVQ) wurde gebildet. Der Pulsdruck (PD=S-D±SD) Blutdruck wurde berechnet. Statistische Methoden: T-Test, bivariate Korrelation, univariate und lineare Regressionen. Ergebnisse. Die Diabetiker (Diabetesdauer 8,1±5,8 Jahre) waren signifikant ubergewichtiger (p
Published: 2008
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34. Glucagon as a determinant of fibrinolytic activity in men with different stages of glucose tolerance: impact of glucagon on fibrinolysis

Author: Cabriele Koehler, Gilvina Siegert, Markolf Hanefeld, Elena Henkel, and Sarsta Gallo
Subjects: Male, endocrine system, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Type 2 diabetes, Biology, Glucagon, Impaired glucose tolerance, Insulin resistance, Internal medicine, Fibrinolysis, Glucose Intolerance, Plasminogen Activator Inhibitor 1, medicine, Humans, Pancreatic hormone, Aged, Insulin, nutritional and metabolic diseases, Hematology, General Medicine, Glucose Tolerance Test, Middle Aged, medicine.disease, Postprandial, Endocrinology, Diabetes Mellitus, Type 2, Area Under Curve, Tissue Plasminogen Activator, Insulin Resistance, hormones, hormone substitutes, and hormone antagonists
Abstract: Glucagon plays an important role in postprandial hyperglycemia in type 2 diabetes (T2DM), and coexists with insulin resistance and impaired fibrinolysis. We analyzed the response of plasminogen activator inhibitor-1 (PAI-1) to a lipid-glucose-protein test and the relationship between glucagon and PAI-1, tissue plasminogen activator (t-PA) and PAI-1/t-PA in 26 men with normal glucose tolerance (NGT), nine with impaired glucose tolerance (IGT) and 12 with T2DM. Fasting and postprandial PAI-1 were higher in T2DM versus NGT (P < 0.05). In univariate analysis in NGT, fasting and area under the curve (AUC) PAI-1 showed a strong relationship with fasting (P = 0.003, P = 0.006) and postprandial (P = 0.041, P = 0.045) glucagon, t-PA with fasting glucagon (P = 0.014), and PAI-1/t-PA with fasting (P = 0.047) and AUC glucagon (P = 0.017). In IGT fasting, AUC PAI-1 and PAI-1/t-PA were associated with AUC glucagon (P = 0.035, P = 0.032, P = 0.023). In NGT with the fasting metabolic parameters and insulin resistance as independent variables, fasting glucagon remained an independent covariate for PAI-1 and PAI-1/t-PA. In another model, postprandial glucagon was independently associated with PAI-1/t-PA in NGT (P < 0.05). Besides the already established determinants, we found an independent association between glucagon and fibrinolysis in NGT. Further studies are needed to identify the link between glucagon, insulin resistance and hemostasis.
Published: 2007

35. Der Pulsdruck bei Typ-2–Diabetikern mit Herzinfarkt: die DIG Studie

Author: Markolf Hanefeld, C Köhler, S. Gallo, Patrick A. Ott, and Elena Henkel
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2007
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36. SP457CCR2 INHIBITOR CCX140 EFFECTIVE IN PHASE 2 CLINICAL TRIAL IN DIABETIC NEPHROPATHY

Author: Jana Psottova, Pirow Bekker, Heidrun Mehling, Thomas J. Schall, Elena Henkel, Dick de Zeeuw, Antonia Potarca, György Paragh, and Christopher Hasslacher
Subjects: Diabetic nephropathy, Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, Urology, Phases of clinical research, medicine.disease, business
Published: 2015
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37. Risikofaktoren für Intima-Media-Verdickung: Ist Adiponektin ein unabhängiger Risikofaktor? Die RIAD Studie

Author: Markolf Hanefeld, C. Köhler, K. Fücker, Elena Henkel, and Frank Schaper
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2006
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38. Glukagon determiniert PAI-1 und t-PA – Aktivität bei Männern mit normaler Glukosetoleranz

Author: Elena Henkel, C. Koehler, G. Siegert, and Markolf Hanefeld
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2006
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39. Beziehung zwischen Metabolischem Syndrom und Gefäßendothel – eine Beobachtung der RIAD-Studie

Author: C. Koehler, Markolf Hanefeld, Frank Schaper, and Elena Henkel
Subjects: Endocrinology, Diabetes and Metabolism
Published: 2006
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40. 40(th) EASD Annual Meeting of the European Association for the Study of Diabetes : Munich, Germany, 5-9 September 2004

Author: S. Artigas, A V Dreval, Mark I. McCarthy, C Watson, Peter H. Bennett, M Quint, Y Ikeda, E Alpert, F Schiele, H Sekihara, Erik Gylfe, P Lowe, J Kuhlmann, Alain Golay, V Longo, Shahidul Alam Khan Akm., L G Mantovani, M Zawodniak-Szalapska, G Winkler, T Harrity, L Virág, U Johne, Kuo S-W., Linda C Tapsell, J Rodriguez, Michel Komajda, K Kankova, Carole A. Cull, M Sporna, E Estilles, U Ribel, M C Spruce, E Buzzigoli, T Prazak, J K McLaughlin, M K Lingohr, M Lim, F Calara, A Siebenhofer, G Meregalli, Roberto Anichini, A D Baron, R Kurashvili, P C Butler, G I Fantus, T. E. De Gooyer, Park Y-M., R. Walther, S Heinrich, Agnieszka Zawiejska, S Mukherjee, Nikolaos Papanas, G Wong, Ian D. Caterson, David M. Maahs, Shuichi Kaneko, Alexandra E. Butler, Francisco Javier Ampudia-Blasco, O N Kong, Attali J-R., C A Hedman, K Oshinyemi, Nicolle Müller, I C Cranston, N Okumus, M V Vlaiculescu, Balasubramanian Ravikumar, W W Cheatham, K Mukasa, K B Biswas, Annunziata Lapolla, Phil McEwan, G Mader, Gilles Chassot, Dragi Anevski, Werner A. Scherbaum, M Donath, C Hesselmann, R A Gandhi, David E. Moller, Ezio Bonifacio, C Garcia, V Ifandi, P Hornnes, Nieuwenhoven Fav., C Puech, S Pérez-Del-Pulgar, Kim S-R., G Hines, C Rubio Terrés, Michael Gaster, N. Hosszufalusi, A Scholze, Andrew A. Young, Stavros Liatis, F Hariri, S Tan, Paul Valensi, Allan E. Karlsen, J Kim, E. Moberg, J Kaiser, L Berman, G Nelson, A Altkrüger, P Kothare, D B Cook, S Doran, G. van Dijk, Shahnaz Shahinfar, Kim C-S., P Stahl, M Manousaki, S Sigrist, S K Lim, M. P. Stern, A Guberti, C Rezzani, J McKenney, Karl Thomaseth, Sofia Carlsson, M Julia, R Brillante, I Rubesova, T Darkow, E Matsumoto, Wendy M. Macfarlane, M Di Martino, G Bardini, Rossella Menghini, D Duhot, E Farcasiu, Annalisa Natalicchio, I Lindner, J Buvat, Christian L. Brand, Harry Dorchy, Iwona Pietrzak, Z T Luo, P Home, M Ekelund, Jesper Gromada, Kristine Færch, F Piarulli, H Kim, R Mentel, Zsuzsanna K. Zsengellér, Dullaart Rpf., Anton Luger, Thomas A. Pearson, V Manicardi, P Rösen, Feng Y-M., R Morganti, Lars Hansen, Demuth H-U., Haruo Kasai, A Shostak, Rudi Steffensen, G Taylor, Markolf Hanefeld, C Santini, E Hamaguchi, Roberto Miccoli, F Storms, M Cooper, Y Lee, Allison E. Aiello, P Smith, T Suehiro, K Treece, M Waluś, Timothy A Welborn, Simone Baltrusch, E Kontela, S Chai, J Crean, H Yokoyama, Johan G. Eriksson, Rafael Hernández Hernández, J Rodríguez-Saldaña, M P Tornero, G Formoso, D. Lovell, E Bingham, A Mylonakis, M Manteghetti, D Fedele, Antonio Martín-Duce, Ralph A. DeFronzo, D Salcedo, Kurt Højlund, Antonio Petrone, Sheu Whh., C Gutierrez, Flavia Pricci, S Kurita, Z G Abbas, M M Benedetti, Philippe A. Halban, Daniel J. Cox, O Ljungkvist, Justine Davies, J Palsgaard, Lars Sjöström, E Bosi, L Janin-Manificat, W. F. Kelly, M. Fernandez, E Colak, O V Mulyarchik, B Kronshage, F Lang, M Erfurth, Takashi Kadowaki, N Jendrike, U Walter, J Wishart, Y. Neye, D Kim, N Furuhashi, M Barsotti, D Florow, L Ke, L Borgquist, N C Jackson, Ffolliott M. Fisher, V Baskar, K Yoshioka, Bryan A. Wolf, G Chabrier, R Skoumal, Livio Luzi, H Kose, I Pharisien, B. Klein, H Winiarska, M C Johnson, L Griffiths, Nonna Kravchun, C Combe, Baptist Gallwitz, J Zdychova, L Skorda, Jorma Ilonen, W Gao, I N Steen, A Terrinoni, P D Ambery, W Kern, C M Kusminski, Cho M-H., Paolo Pozzilli, Louise G. Grunnet, E Schönle, David R Matthews, Robert W. Taylor, Y Cohen, Kim H-S., M P Eccles, N B Tutuncu, D McDowell, Richard M. Bergenstal, K Takamatsu, T Steiner, Jaan Palgi, Valdemar Grill, N Niculescu, G Federici, S Lehto, P. M. McKeigue, M Barone, Michael E. Trautmann, S Smirnov, J Mannion, M Eto, C Rousseau, M Conti, C S Ernest, Antonio Ceriello, D H Schweitzer, Jung E-D., Andreas Festa, Avijit Lahiri, A Shepelkevich, A Murro, A Kollmann, Jonathan R.S. Arch, R Landgraf, Son H-Y., I Engelsberger, E Agardh, S Rodríguez-Mulero, P J Kraml, K Lee, D. F. Du Toit, E Kim, G Fadini, Williams Ajk., Philip Home, M B Antcieferov, C Perlemoine, D Perrea, Song X-L., D Ruggieri, Krister Bokvist, Heidi Sørensen, Bilbao, G Yoshino, J P Taylor, Shen H-M., S M Furier, R Urquhart, J Wohlgelernter, Jianping Weng, T. Baba, Q Hong, C Silva, Castaigne J-P., M Felaco, X X Zhang, M Jaroň, Milla Rosengård-Bärlund, J G Papp, Toshio Miyata, Lervang H-H., Park M-K., I Kinalska, A Long, Oomen Phn., N Kogawa, Ippolita Patrizia Patera, S. Karadeniz, Dinesh Selvarajah, D S Chung, A Wensaas, Richard Imrich, M Recasens, J Ruxer, O Buchea, E Wilpart, S P Stepanenko, Le Ttd., H Ohgawara, Mariaconsuelo Valentini, A Mondok, M Peltonen, Marianne O. Larsen, K Chatzianagnostou, Agneta Ståhle, A L Ferrari, L Bordier, F Maingrette, A Matsuda, G Vukomanovic, Jakob D. Wikstrom, T Yamakita, E Gorostiaga, J Jin, B Gopalan, Heinz Drexel, S Hewitt, Rury R. Holman, C Dieterle, T L Ruchti, N Asatiani, M Sidira, A Iezzi, A J Sommerfield, D Châtenet, M L Olsen, R Bergemann, C Koehler, T L Kuraeva, B Balas, Christian Berne, E Santos-Mazo, G Smith, A Siejka, R Kožnarová, A Mattina, S Sheikh, A Adomeit, M Rasmussen, J. Fagerudd, N Busciantella Ricci, Nuria Vilarrasa, E Hammar, T L Thoms, L Aydın, Ron G. Rosenfeld, A Nikolajuk, R Gos, C L Morgan, H L Yu, D Dheelchand, S Ramrath, N Boudriga, Jerome I. Rotter, C Jahannault, W M Weston, Folke Lindgärde, M Hertlova, D Knight, A Monroy-Mayorga, E Pardini, A Chamson-Reig, B Franke, Janie McCluskey, Joseph Bryan, C Nikolopoulou, Christie M. Ballantyne, Fausto Santeusanio, L Pegoraro, M Lee, A Klimenko, S Jaiveer, K. Pettersson-Fernholm, Michael A. 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Jensen, G, Fisher, A, Petrovsky, N, Srikusalanukul, W, Budge, M, Trifunovic zamaklar, D, Zivkovic, M, Jelic, V, Vukomanovic, G, Ristic, A, Seferovic, P, Costa, J, Duarte, S, Manley, S, Sailesh, S, Venkataraman, A, Haider, Y, Groza, I, Oprean, M, Ardelean, A, Morosanu, A, Darkow, T, Vanderplas, A, Mamas, M, Mcelduff, P, Burns, J, Edwards, R, Fitchet, A, Young, R, Gibson, J, Lichiardopol, R, Niculescu, N, Totora, A, Pencea, C, Tomescu, I, Cinteza, M, Manicardi, V, Coscelli, C, Navazio, A, Catellani, E, Michelini, M, Dall'Asta, D, Guberti, A, Piazza, A, Gasparini, E, Pantaleoni, M, Guiducci, U, Manari, A, Sejil, S, Janand delenne, B, Avierinos, J, Habib, G, Labastie, N, Vague, P, Lassmann vague, V, Luźniak, P, Tatoń, J, Wojciechowska Luźniak, A, Zairis, M, Lyras, A, Patsourakos, N, Tsirimbis, V, Foussas, S, Lupón, J, Urrutia, A, Herreros, J, González, B, Coll, R, Altimir, S, Prats, M, Valle, V, Abreu padí, C, Rábago, G, Ivanova, L, Brasacchio, D, Harno, E, Keenan, A, Li, H, Lu, Z, Ke, L, Liu, H, Jeong, I, Chae, M, Choi, M, Yoo, H, Kim, C, Yun, M, Na, M, Kang, Y, Kong, O, Son, S, Kim, I, Tanaka, N, Hosoi, M, Matsuyama, Y, Fukumoto, M, Yamakita, T, Yoshioka, K, Ishii, T, Sato, T, Fujii, S, Aoki, T, Shibata, T, Mizutani, N, Suzuki, J, Fowelin, J, Samuelsson, P, Brandrup wogsen, G, Okumura, K, Tokmakova, A, Staroverova, D, Antcieferov, M, Shutichina, I, Kuntchevich, G, Vriesendorp, T, Morélis, Q, Legemate, D, Schaper, F, Mainas, E, Gkioulmpasanis, I, Panagiotou, I, Vassilikos, G, Skorda, L, Sidira, M, Christoforidou, M, Alaveras, A, Artikis, V, Evdemon, E, Lechleitner, M, Koch, T, Ebenbichler, C, Sturm, W, Moretti, L, Moruzzo, D, Boldrini, E, Pandolfo, C, Kameyama, M, Iwasa, R, Cho, M, Nam, J, Huh, K, Kaplar, M, Paragh, G, Erdei, A, Csongradi, E, Garai, I, Varga, J, Galuska, L, Udvardy, M, Higa, M, Kaneko, Y, Hiroi, N, Koziarska, D, Nowacki, P, Majkowska, L, Luzniak, P, Wojciechowska luźniak, A, Tushuizen, M, Nieuwland, R, Snoeck, D, Sturk, A, Diamant, M, Aguiar, L, Bahia, 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D, Torjesen, P, Kilhovd, B, Berg, T, Sandvik, L, Hanssen, K, Mentink, C, Donchenko, G, Stepanenko, S, Maingrette, F, Deng, H, Lindenmair, A, Freudenthaler, A, Baumgartner parzer, S, Nizheradze, K, Khoruzhenko, A, Tronko, N, Sheu, W, Ou, H, Shen, H, Lin, T, Wu, H, Yang, C, Mogylnytska, L, Schmoelzer, I, Davies, J, Band, M, Struthers, A, Prázný, M, Škrha, J, Kasalová, Z, Neelotpol, S, Jahan, P, Kauschke, S, Harrop, C, Schäfer, A, Widder, J, Eigenthaler, M, Walter, U, Uchimura, I, Ikebukuro, M, Kaibara, M, Hirata, M, Helal, R, Pervin, F, Yang, X, Jansson, P, Nagaev, I, Jack, M, Carvalho, E, Sunnerhagen, K, Cam, M, Cushman, S, Smith, U, Creely, S, Farmer, J, Gustafson, B, Kusminski, C, Krusinova, E, Wohl, P, Klementova, M, Lanska, V, Mcdougall, C, Kelly, I, Abbas, Z, Lutale, J, Archibald, L, Karunajeewa, H, Stingemore, N, Stuccio, G, Mcgechie, D, Muller, L, Hak, E, Goudzwaard, W, Montorsi, F, Homering, M, Sprenger, K, Goldstein, I, Asnaghi, V, Ferrari, G, Rastaldi, M, Gabellini, D, Dell'Antonio, G, Maestroni, A, Ruggieri, D, Luzi, L, Piemonti, L, Zerbini, G, Anafaroglu, I, Tutuncu, N, Sultana, M, Siddiqua, N, Iwasaki, T, Nakajima, A, Yoneda, M, Mukasa, K, Tanaka, S, and Sekihara, H
Subjects: 0303 health sciences, medicine.medical_specialty, business.industry, EASD, Endocrinology, Diabetes and Metabolism, Human physiology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Family medicine, Internal Medicine, Medicine, business, 030217 neurology & neurosurgery, 030304 developmental biology
Published: 2004

41. Adiponectin und Leptin: postprandialer Verlauf und die Beziehungen zu den Parametern der Insulin-Glukose-Homöostase in verschiedenen Glukosetoleranzstadien

Author: C. Köhler, K. Fücker, M. Menschikowski, Markolf Hanefeld, and Elena Henkel
Subjects: Nutrition and Dietetics, Medicine (miscellaneous)
Abstract: Adiponectin (ADPN) und Leptin (L) sind spezifische Hormone der Adipozyten und spielen eine wichtige Rolle in der Regulation des Glukosemetabolismus. Das Ziel war zu prufen, wie verhalten sich ADPN und L in der postprandialen (pp) Phase und welche Beziehungen bestehen zwischen den ADPN, L und den metabolischen Parametern in den verschiedenen Glukosetoleranzstadien. Methoden. Zu einem Lipid-Glukosetoleranztest wurden Manner im Alter zwischen 40 und 70 Jahre und BMI
Published: 2003
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42. Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study

Author: Markolf, Hanefeld, Carsta, Koehler, Katja, Fuecker, Elena, Henkel, Frank, Schaper, and Theodora, Temelkova-Kurktschiev
Subjects: Adult, Blood Glucose, Male, Arteriosclerosis, Fasting, Glucose Tolerance Test, Middle Aged, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Risk Factors, Glucose Intolerance, Insulin Secretion, Humans, Insulin, Female, Insulin Resistance, Sex Distribution, Aged, Proinsulin
Abstract: Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance.This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories.All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance.Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.
Published: 2003

43. Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals

Author: Carsta Koehler, Frank Schaper, Elena Henkel, Markolf Hanefeld, Theodora Temelkova-Kurktschiev, and Katja Fuecker
Subjects: Tunica media, Adult, Blood Glucose, Male, medicine.medical_specialty, medicine.medical_treatment, Population, Coronary Disease, Comorbidity, Risk Assessment, Statistics, Nonparametric, Waist–hip ratio, Risk Factors, Internal medicine, Confidence Intervals, Diabetes Mellitus, Medicine, Humans, Prospective Studies, Risk factor, education, Aged, Ultrasonography, education.field_of_study, Analysis of Variance, business.industry, Insulin, Glucose Tolerance Test, Middle Aged, Postprandial Period, Health Surveys, medicine.anatomical_structure, Endocrinology, Postprandial, Carotid Arteries, Intima-media thickness, Female, Cardiology and Cardiovascular Medicine, business, Tunica Intima, Body mass index
Abstract: Postprandial (pp) hyperglycemia--frequently associated with an increase in cardiovascular risk factors--may be damaging for the endothelium. So far, little information exists how glucose, insulin and lipids may affect atherosclerosis in the pp state. Therefore, we evaluated the relationship of pp hyperglycemia, insulin secretion and coronary risk factors to intima-media thickness (IMT) in a non-diabetic risk population. In 403 subjects (147 males, 256 females), aged 40-70 years, in the majority relatives of index cases with type 2 diabetes--a 75 g oral glucose tolerance test was performed together with measurement of insulin fractions, various risk factors and IMT of the common carotid artery. We found a continuous rise of 2h pp insulin fractions along the quintiles of 2h pp plasma glucose. A significant increase of body mass index, waist to hip ratio, triglycerides and decrease of HDL-cholesterol was observed in the top quintile of 2h pp plasma glucose (8.24or = pp plasma glucose11.1 mmol/l). Albuminuria was significantly enhanced in the 5th quintile. In parallel, IMT was significantly increased in the 5th quintile versus the bottom quintile of 2 h and maximal glucose (range 11.7-15.3 mmol/l) postprandially. After age and sex adjustment pp glucose and C-peptide, total cholesterol, triglycerides and HDL-cholesterol but not fasting plasma glucose were significantly correlated to IMT. In multivariate analysis age, male sex, pp plasma glucose, total and HDL-cholesterol were found to be independent risk factors for increased IMT. In conclusion, our data in a non-diabetic European risk population show that the two top quintiles of pp plasma glucose are associated with a clustering of standard risk factors. Corresponding to this clustering of risk factors IMT was significantly increased in the top quintile of 2 h and maximal pp plasma glucose. These data show that pp hyperglycemia may exert a noxious impact on the arterial wall together with a cluster of anomalies typical for the metabolic syndrome.
Published: 1999

44. Relationship between fasting plasma glucose, atherosclerosis risk factors and carotid intima media thickness in non-diabetic individuals

Author: Markolf Hanefeld, Frank Schaper, C. Koehler, Katja Fuecker, Elena Henkel, Theodora Temelkova-Kurktschiev, Gabriele Siegert, and A. Hahnefeld
Subjects: Blood Glucose, Male, medicine.medical_specialty, Arteriosclerosis, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Body Mass Index, chemistry.chemical_compound, Waist–hip ratio, High-density lipoprotein, Sex Factors, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Albuminuria, Humans, Insulin, Obesity, Prospective Studies, Triglycerides, Ultrasonography, Family Health, Glycated Hemoglobin, Analysis of Variance, Cholesterol, business.industry, Cholesterol, HDL, Age Factors, Fasting, Middle Aged, medicine.disease, Plasminogen Inactivators, Endocrinology, Carotid Arteries, Intima-media thickness, chemistry, Diabetes Mellitus, Type 2, Body Constitution, Female, business, Tunica Intima, Tunica Media, Plasminogen activator, Body mass index
Abstract: We analysed the relationship between fasting plasma glucose, carotid intima media thickness and some atherosclerosis risk factors in 307 non-diabetic individuals. Male (n = 120) and female subjects (n = 187) with a familial history of Type II diabetes mellitus and/or obesity and hyperlipoproteinaemia were examined in the age group 40–70 years. Plasma triglycerides, total and high-density-lipoprotein cholesterol, plasminogen activator inhibitor were measured by conventional methods. Specific insulin, proinsulin and C-peptide were measured by specific enzyme immunoassay. Intima media thickness increased in quintiles for fasting plasma glucose in men, but not in women. There was a rise of triglycerides, body mass index, waist to hip ratio, plasminogen activator inhibitor, true insulin, proinsulin, C-peptide and a decrease of high-density-lipoprotein cholesterol in quintiles for fasting plasma glucose. Fasting plasma glucose was found to be significantly positively correlated to intima media thickness, body mass index, waist to hip ratio, haemoglobin A1 c, insulin, C-peptide, triglycerides, plasminogen activator inhibitor and significantly negatively correlated to high density lipoprotein cholesterol. However, the correlation of fasting plasma glucose to intima media thickness was no longer significant after adjustment for age and sex. After adjustment for age and sex intima media thickness was significantly correlated to body mass index, total cholesterol, triglycerides, albuminuria and inversely correlated to high-density-lipoprotein cholesterol. In multivariate analysis age, male sex, high-density-lipoprotein cholesterol and total cholesterol were significant determinants of intima media thickness. Our data suggest that a weak association exists between fasting plasma glucose and intima media thickness, which may be mediated by a clustering of risk factors in the upper range of non-diabetic fasting plasma glucose level with a central role for dyslipidaemia. [Diabetologia (1998) 41: 706–712]
Published: 1998

45. Light-to-moderate alcohol consumption, risk factor profile and early atherosclerosis: the RIAD Study

Author: Elena Henkel, Carsta Koehler, Markolf Hanefeld, and Theodora Temelkova-Kurktschiev
Subjects: Male, Time Factors, Alcohol Drinking, Arteriosclerosis, business.industry, Risk Factors, Environmental health, Humans, Medicine, Female, Risk factor, Cardiology and Cardiovascular Medicine, business, Alcohol consumption
Published: 2001
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46. Impaired glucose tolerance is not associated with lipidintolerance

Author: Theodora Temelkova-Kurktschiev, Carsta Koehler, W. Leonhardt, Markolf Hanefeld, and Elena Henkel
Subjects: Impaired glucose tolerance, medicine.medical_specialty, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, General Medicine, medicine.disease, business
Published: 2000
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47. Leucocytes count and fibrinogen level are associated with carotid and femoral intima-media thickness

Author: Elena Henkel, Theodora Temelkova-Kurktschiev, Frank Schaper, Markolf Hanefeld, and Sabine Fischer
Subjects: Fibrinogen levels, medicine.medical_specialty, Intima-media thickness, business.industry, Ophthalmology, medicine, Cardiology and Cardiovascular Medicine, business
Published: 2000
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48. Microalbuminuria is an independent risk factor for increased intima-media thickness: Data from the riad study

Author: Carsta Koehler, Theodora Temelkova-Kurktschiev, Elena Henkel, Markolf Hanefeld, and Frank Schaper
Subjects: medicine.medical_specialty, Intima-media thickness, business.industry, Internal medicine, medicine, Cardiology, Microalbuminuria, Risk factor, Cardiology and Cardiovascular Medicine, medicine.disease, business
Published: 1999
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49. Is the newly suggested fasting plasma glucose cut-off point for the diagnosis of diabetes the right one?

Author: Katja Fuecker, C. Koehler, Theodora Temelkova-Kurktschiev, Frank Schaper, Markolf Hanefeld, and Elena Henkel
Subjects: Glucose tolerance test, Plasma glucose, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Endocrinology, Diabetes and Metabolism, medicine.disease, Cut off point, Endocrinology, Reference values, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, business
Published: 1999
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50. Observations

Author: Elena Henkel, Theodora Temelkova-Kurktschiev, K Karrei, Markolf Hanefeld, and C. Koehler
Subjects: Glucose tolerance test, medicine.medical_specialty, medicine.diagnostic_test, biology, business.industry, Endocrinology, Diabetes and Metabolism, C-reactive protein, Inflammation, medicine.disease, Impaired glucose tolerance, Type ii diabetes, Endocrinology, Internal medicine, Diabetes mellitus, Reference values, Internal Medicine, medicine, biology.protein, Subclinical inflammation, medicine.symptom, business
Published: 2002
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