Lucien Marchand1, Arnaud Thivolet2, Stéphane Dalle3,4, Karim Chikh5, Sophie Reffet6, Julien Vouillarmet6, Nicole Fabien7, Christine Cugnet-Anceau6,4, Charles Thivolet6,8. 1. Department of Endocrinology and Diabetes, Hospices Civils de Lyon, Lyon-Sud Hospital, 165 chemin du Grand Revoyet, Pierre-Bénite, 69310, France. lucien.marchand@chu-lyon.fr. 2. Department of Radiology, Hospices Civils de Lyon, Lyon, France. 3. Department of Dermatology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France. 4. ImmuCare (Immunology Cancer Research), Hospices Civils de Lyon, Lyon, France. 5. Department of Biochemistry, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France. 6. Department of Endocrinology and Diabetes, Hospices Civils de Lyon, Lyon-Sud Hospital, 165 chemin du Grand Revoyet, Pierre-Bénite, 69310, France. 7. Department of Immunology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Bénite, France. 8. CarMeN Laboratory (INSERM U1060, INRA U1235, Université Claude Bernard Lyon1, INSA-Lyon), Lyon 1 University, Oullins, France.
Abstract
AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FD patient was not found in other FD subjects, but glucagon response was blunted in another FD patient. Pancreas volume was decreased at diabetes onset in 2 FD patients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.
AIMS: Programmed cell death-1 and programmed death ligand 1 (PD-1/PD-L1) inhibitors restore antitumor immunity, but many autoimmune side-effects have been described. Diabetes mellitus is a rare complication, and little data concerning its pathophysiology and phenotype have been published. This study aimed to describe both pancreatic endocrine and exocrine functions, immunological features and change in pancreas volume in subjects with diabetes mellitus induced by PD-1 and PD-L1 inhibitors. METHODS: We analyzed the data of six subjects treated with immunotherapy who presented acute diabetes. RESULTS: There were five men and one woman. Median age was 67 years (range 55-83). Three subjects were treated with nivolumab, two with pembrolizumab and one with durvalumab. Median time to diabetes onset after immunotherapy initiation was 4 months (range 2-13). Four patients presented fulminant diabetes (FD); none of these had type 1 diabetes (T1D)-related autoantibodies, none of them had T1D or FD-very high-risk HLA class II profiles. The bi-hormonal endocrine and exocrine pancreatic failure previously reported for one FDpatient was not found in other FD subjects, but glucagon response was blunted in another FDpatient. Pancreas volume was decreased at diabetes onset in 2 FDpatients, and all patients presented a subsequent decrease of pancreas volume during follow-up. CONCLUSIONS: In the patients presented herein, immunotherapy-induced diabetes was not associated with T1D-related autoantibodies. The hormonal and morphological analysis of the pancreatic glands of these six cases contributes to the understanding of the underlying and probably heterogeneous mechanisms. There is a need to find biomarkers to identify patients at risk to develop these new forms of diabetes at early stages of the process to prevent ketoacidosis and to evaluate preventive strategies.
Authors: Osamah A Hakami; Julia Ioana; Shahzad Ahmad; Tommy Kyaw Tun; Seamus Sreenan; John H McDermott Journal: Endocrinol Diabetes Metab Case Rep Date: 2019-03-05
Authors: Jeroen M K de Filette; Joeri J Pen; Lore Decoster; Thomas Vissers; Bert Bravenboer; Bart J Van der Auwera; Frans K Gorus; Bart O Roep; Sandrine Aspeslagh; Bart Neyns; Brigitte Velkeniers; Aan V Kharagjitsingh Journal: Eur J Endocrinol Date: 2019-09 Impact factor: 6.664