Megu Yamaguchi Baden1, Akihisa Imagawa2, Norio Abiru3, Takuya Awata4, Hiroshi Ikegami5, Yasuko Uchigata6, Yoichi Oikawa7, Haruhiko Osawa8, Hiroshi Kajio9, Eiji Kawasaki10, Yumiko Kawabata5, Junji Kozawa1, Akira Shimada7, Kazuma Takahashi11, Shoichiro Tanaka12, Daisuke Chujo9, Tomoyasu Fukui13, Junnosuke Miura14, Kazuki Yasuda15, Hisafumi Yasuda16, Tetsuro Kobayashi17, Toshiaki Hanafusa18. 1. 1Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Osaka Japan. 2. 2Department of Internal Medicine (I), Osaka Medical College, 2-7 Daigakucho, Takatsuki, Osaka 569-8686 Japan. 3. 3Department of Endocrinology and Metabolism, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 4. 4Department of Diabetes, Endocrinology and Metabolism, International University of Health and Welfare Hospital, Otawara, Tochigi Japan. 5. 5Department of Endocrinology, Metabolism and Diabetes, Kindai University Faculty of Medicine, Higashi-osaka, Osaka Japan. 6. 6Tokyo Women's Medical University Medical Center East, Tokyo, Japan. 7. 7Department of Endocrinology and Diabetes, School of Medicine, Saitama Medical University, Saitama, Japan. 8. 8Department of Laboratory Medicine, Ehime University School of Medicine, Toon, Ehime Japan. 9. 9Department of Diabetes, Endocrinology, and Metabolism, Center Hospital of the National Center for Global Health and Medicine, Tokyo, Japan. 10. 10Diabetes Center, Shin-Koga Hospital, Kurume, Fukuoka Japan. 11. 11Faculty of Nursing and Graduate School of Nursing, Iwate Prefectural University, Takizawa, Iwate Japan. 12. Ai Home Clinic Toshima, Tokyo, Japan. 13. 13Department of Internal Medicine, Division of Diabetes and Endocrinology, Showa University School of Medicine, Tokyo, Japan. 14. 14Diabetes Center, Tokyo Women's Medical University School of Medicine, Tokyo, Japan. 15. 15Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. 16. 16Division of Health Sciences, Department of Community Health Sciences, Kobe University Graduate School of Health Sciences, Kobe, Hyogo Japan. 17. 17Okinaka Memorial Institute for Medical Research, Tokyo, Japan. 18. Sakai City Medical Center, Sakai, Osaka Japan.
Abstract
AIMS: We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy. METHODS: We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search. RESULTS: Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63 years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155 days and ranged from 13 to 504 days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ± standard deviation or median (first quartile-third quartile) glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248 mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive. CONCLUSIONS: Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations.
AIMS: We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to anti-programmed cell death-1 therapy. METHODS: We analyzed the detailed data of 22 patients that were collected using a Japan Diabetes Society survey and a literature database search. RESULTS: Among the 22 patients, 11 (50.0%) met the criteria for fulminant type 1 diabetes and 11 (50.0%) met the criteria for acute-onset type 1 diabetes. The average patient age was 63 years. The mean duration between the date of the first anti-PD-1 antibody injection and development of type 1 diabetes was 155 days and ranged from 13 to 504 days. Flu-like symptoms, abdominal symptoms, and drowsiness were observed in 27.8, 31.6, and 16.7% patients, respectively. Mean ± standard deviation or median (first quartile-third quartile) glucose levels, HbA1c levels, urinary C-peptide immunoreactivity levels, and fasting serum C-peptide immunoreactivity levels were 617 ± 248 mg/dl, 8.1 ± 1.3%, 4.1 (1.4-9.4) μg/day, and 0.46 (0.20-0.70) ng/ml, respectively. Seventeen of 20 patients (85.0%) developed ketosis, and 7 of 18 patients (38.9%) developed diabetic ketoacidosis. Ten of 19 patients (52.6%) showed at least one elevated pancreatic enzyme level at the onset and two of seven patients showed this elevation before diabetes onset. Only one of 21 patients was anti-glutamic acid decarboxylase antibody positive. CONCLUSIONS: Anti-programmed cell death-1 antibody-related type 1 diabetes varies from typical fulminant type 1 diabetes to acute-onset type 1 diabetes. However, diabetic ketoacidosis was frequently observed at the onset of diabetes. An appropriate diagnosis and treatment should be provided to avoid life-threatening metabolic alterations.
Entities:
Keywords:
Anti-PD-1 antibody; Fulminant type 1 diabetes; Immune-checkpoint inhibitors; Nivolumab; Pembrolizumab; Type 1 diabetes
Authors: Andreas Neu; Sabine E Hofer; Beate Karges; Rudolf Oeverink; Joachim Rosenbauer; Reinhard W Holl Journal: Diabetes Care Date: 2009-06-23 Impact factor: 19.112