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Werner F Blum University Children’s Hospital, Giessen, Germany

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Abdullah Alherbish Al Habib Medical Group, Riyadh, Saudi Arabia

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Afaf Alsagheir King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Ahmed El Awwa Department of Pediatric Endocrinology & Diabetes, Hamad Medical Center, Doha, Qatar

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Walid Kaplan Tawam Hospital, Al Ain, UAE

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Ekaterina Koledova Global Medical Affairs Endocrinology, Merck KGaA, Darmstadt, Germany

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Martin O Savage William Harvey Research Institute, Barts and the London School of Medicine & Dentistry, London, UK

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Introduction The growth hormone (GH)–insulin-like growth factor (IGF)-I axis is the principle endocrine system regulating linear growth in children ( 1 ). Linked to the nutritional status of the individual, GH is a potent stimulator of IGF-I

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Martin Bidlingmaier Medizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians University, Munich, Germany

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Helena Gleeson Department of Endocrinology, Queen Elizabeth Hospital, Birmingham, UK

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Ana-Claudia Latronico Department of Internal Medicine, Discipline of Endocrinology and Metabolism, Sao Paulo Medical School, University of Sao Paulo, Sao Paulo, Brazil

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Martin O Savage Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, London, UK

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treatment. In the 1990s, insulin-like growth factor (IGF)-binding protein 3 (IGFBP-3) was often used as an indicator of GH levels, particularly in children younger than 8 years, probably because of the difficulties at that time of measuring IGF-I at low

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Monika Bilic Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Canada

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Huma Qamar Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Canada

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Akpevwe Onoyovwi Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada

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Jill Korsiak Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada

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Eszter Papp Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada

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Abdullah Al Mahmud Nutrition and Clinical Services Division, icddr,b, Dhaka, Bangladesh

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Rosanna Weksberg Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada
Molecular and Medical Genetics, University of Toronto, Toronto, Canada
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada

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Alison D Gernand Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA

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Jennifer Harrington Division of Endocrinology, Hospital for Sick Children, Toronto, Canada

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Daniel E Roth Centre for Global Child Health, Hospital for Sick Children, Toronto, Canada
Department of Nutritional Sciences, University of Toronto, Toronto, Canada
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Canada

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improve growth-related outcomes. The insulin-like growth factor (IGF) axis includes several signal and binding proteins, many of which are under the regulation of growth hormone. IGF-I is the primary regulator of fetal growth, and its circulating

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M Krause Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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H Frederiksen Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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K Sundberg Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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F S Jørgensen Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Denmark

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L N Jensen Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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P Nørgaard Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Denmark

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C Jørgensen Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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P Ertberg Fetal Medicine Unit, Department of Obstetrics and Gynecology, Copenhagen University Hospital, Hvidovre, Denmark

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J H Petersen Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Section of Biostatistics, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark

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U Feldt-Rasmussen Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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A Juul Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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K T Drzewiecki Department of Plastic Surgery, Breast Surgery and Burns Treatment, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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N E Skakkebaek Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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A M Andersson Department of Growth and Reproduction & International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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factor I (IGF-I) and its major binding protein: insulin-like growth factor-binding protein-3 (IGFBP3). IGF-I and IGFBP3 were both measured by a chemiluminescence immunoassay on the IDS-iSYS automated platform (Immuno Diagnostic Systems, IDS) at the

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Elvira C Arellanes-Licea Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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José Ávila-Mendoza Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Elizabeth C Ramírez-Martínez Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Eugenia Ramos Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Nancy Uribe-González Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Carlos Arámburo Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Teresa Morales Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Maricela Luna Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, México

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Research 1993 74 225 – 233. ( https://doi.org/10.1016/0165-3806(93)90008-X ) 19 Aberg ND Brywe KG Isgaard J. Aspects of growth hormone and insulin-like growth factor-I related to neuroprotection, regeneration, and functional plasticity in the

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P R van Dijk Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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S J J Logtenberg Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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K H Groenier Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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N Kleefstra Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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H J G Bilo Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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H J Arnqvist Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands
Diabetes Centre, Departments of Internal Medicine, General Practice, Langerhans Medical Research Group, Department of Internal Medicine, Division of Cell Biology, Faculty of Health Sciences, Isala Clinics, PO Box 10400, 8000 G.K. Zwolle, The Netherlands

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hormone and insulin-like growth factor 1 . Nature Clinical Practice. Endocrinology & Metabolism 2007 3 302 – 310 . ( doi:10.1038/ncpendmet0427 ). 3 Kim JJ Accili D . Signalling through IGF-I and insulin receptors: where is the specificity? Growth Hormone

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Nadia Sabbah Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France
Hôpital de Cayenne, Service d’Endocrinologie et des Maladies Métaboliques, Cayenne, Guyane Française

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Peter Wolf Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France
Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

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Céline Piedvache Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Unité de Recherche Clinique, Le Kremlin-Bicêtre, France

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Séverine Trabado Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin-Bicêtre, France

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Tristan Verdelet Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France

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Catherine Cornu Centre d’Investigation Clinique, INSERM CIC1407/UMR5558, Hospices Civils de Lyon, Bron, France

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Jean-Claude Souberbielle Assistance Publique-Hôpitaux de Paris, Hôpital Necker, Service d’Explorations Fonctionnelles, Paris, France

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Philippe Chanson Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital de Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, France

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://doi.org/10.1159/000493133 ) 12 Alberti C Chevenne D Mercat I Josserand E Armoogum-Boizeau P Tichet J Léger J . Serum concentrations of insulin-like growth factor (IGF)-1 and IGF binding protein-3 (IGFBP-3), IGF-1/IGFBP-3 ratio, and markers of

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Ram P Narayanan Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Bo Fu Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Adrian H Heald Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Kirk W Siddals Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Robert L Oliver Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Julie E Hudson Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Antony Payton Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Simon G Anderson Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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Anne White Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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William E R Ollier Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK
Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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J Martin Gibson Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK
Vascular Research Group, School of Community Based Medicine, Centre for Integrated Genomic Medical Research, Cardiovascular Research Group, Endocrinology and Diabetes, Salford R&D, Department of Endocrinology and Diabetes, Faculty of Medical, Human and Life Sciences, The University of Manchester, Manchester M13 9PT, UK

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mice is associated with persistent renal accumulation of insulin-like growth factor I . Journal of the American Society of Nephrology 1997 8 436 – 444 . 9 Park IS Kiyomoto H Alvarez F Xu YC Abboud HE Abboud SL . Preferential

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R Solomon-Zemler Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

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L Basel-Vanagaite Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel
Felsenstein Medical Research Center, Petach Tikva, Israel
Pediatric Genetics, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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D Steier Day Hospitalization Department, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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S Yakar David B. Kriser Dental Center, Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York, USA

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E Mel Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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M Phillip Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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L Bazak Raphael Recanati Genetic Institute, Rabin Medical Center – Beilinson Hospital, Petach Tikva, Israel

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D Bercovich Tel-Hai College, Tel-Hai, Israel

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H Werner Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Shalom and VardaYoran Institute for Human Genome Research, Tel Aviv University, Tel Aviv, Israel

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L de Vries Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
Jesse Z. and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

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specific (genetic or other) defect can be recognized. Growth and developmental conditions under the umbrella of congenital insulin-like growth factor-1 ( IGF-1 ) deficiencies include: (i) growth hormone (GH) releasing hormone-receptor ( GHRH-R ) defect

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Taísa A R Vicente
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Ívina E S Rocha
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Roberto Salvatori Division of Endocrinology, Division of Endocrinology, National Research Council, Federal University of Sergipe, Aracaju, Sergipe 49060-100, Brazil

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Carla R P Oliveira
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Rossana M C Pereira
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Anita H O Souza
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Viviane C Campos
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Elenilde G Santos
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Rachel D C Araújo Diniz
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Eugênia H O Valença
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Carlos C Epitácio-Pereira
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Mario C P Oliveira
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Andrea Mari Division of Endocrinology, Division of Endocrinology, National Research Council, Federal University of Sergipe, Aracaju, Sergipe 49060-100, Brazil

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Manuel H Aguiar-Oliveira
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Kopchick JJ Liu YL Liu JL . Pancreatic islet-specific expression of an insulin-like growth factor-I transgene compensates islet cell growth in growth hormone receptor gene deficient mice . Endocrinology 2005 146 2602 – 2609 . ( doi:10.1210/en

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