1. Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial
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Yvan Bricault, Gwen Grguric, Valery Gmyr, Eric Renard, Mathieu Rodière, Bruno Guerci, M. Greget, Anaïck Moisan, François Pattou, Cyrille Colin, Sophie Logerot, François Moreau, Frédéric Thony, Jean-Luc Bosson, C. Thivolet, Marie-Ange Pierredon, Sandrine Lablanche, Nadine Pernin, Kanza Benomar, Anne Wojtusciszyn, Jean Champagnac, Béatrice Roche, Christian Noel, Julie Kerr-Conte, Kristina Skaare, Violetta Raverdy, Pierre-Jean Valette, Kristel Le Mapihan, Christian Sengel, Fanny Buron, Thibault Bahoune, Igor Tauveron, Iulian Enescu, Arnaud Muller, Lionel Badet, Virginie Persoons, Marie-Christine Vantyghem, Marc Hazzan, Lucy Chaillous, Thierry Berney, Emmanuel Morelon, Rimed Ezzouaoui, R. Caiazzo, Sophie Borot, Domenico Bosco, Jacques Dantal, Laurence Kessler, Fanelly Torres, Paolo Malvezzi, Pierre-Yves Benhamou, Philippe Baltzinger, Coralie Camillo-Brault, Luc Frimat, Sophie Girerd, Alfred Penfornis, Harald Egelhofer, Jean-Pierre Riveline, Pierre Cattan, Rachel Tetaz, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Centre Hospitalier Universitaire [Grenoble] (CHU), Université de Strasbourg (UNISTRA), CHU Strasbourg, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie [Montpellier] (CHU), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Université de Franche-Comté (UFC), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire d'Hématologie, CHU Grenoble, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Geneva University Hospital (HUG), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord (France), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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Male ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Islets of Langerhans Transplantation ,030230 surgery ,law.invention ,0302 clinical medicine ,Endocrinology ,Randomized controlled trial ,law ,Medicine ,Insulin ,awareness ,Kidney transplantation ,geography.geographical_feature_category ,ddc:617 ,Immunosuppression ,Middle Aged ,Islet ,3. Good health ,surgical procedures, operative ,Treatment Outcome ,Female ,Adult ,medicine.medical_specialty ,endocrine system ,030209 endocrinology & metabolism ,03 medical and health sciences ,Endocrinology & Metabolism ,beta-score ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,Humans ,Hypoglycemic Agents ,improvement ,renal-function ,Glycated Hemoglobin ,Type 1 diabetes ,geography ,business.industry ,medicine.disease ,Kidney Transplantation ,Hypoglycemia ,Transplantation ,Diabetes Mellitus, Type 1 ,quality-of-life ,Quality of Life ,progression ,business ,mellitus - Abstract
International audience; Background Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. Methods In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified (beta-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. Findings Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified (beta-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p\textless0.0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90-5 mL/min (IQR 76-6-94-0) to 71-8 mL/min (59-0-89-0) was observed in islet recipients who had not previously received a kidney graft and from 63 .0 mL/min (55.0-71-0) to 57. 0 mL/min (45-5-65 . 1) in islet recipients who had previously received a kidney graft. Interpretation For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. Copyright (C) 2018 Elsevier Ltd. All rights reserved.
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- 2017
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