Characteristics and clinical course of type 1 diabetes mellitus related to anti-programmed cell death-1 therapy

Abstract

Aims We conducted a national survey to clarify the characteristics and clinical course of type 1 diabetes related to antiprogrammed 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.

Nivolumab‐induced fulminant type 1 diabetes with precipitous fall in C‐peptide level

“…Anti-programmed cell death protein 1 (PD-1) antibodies activate the immune system to attack tumors and are used as anticancer agents. However, anti-PD-1 antibody therapy is reported to induce serious side-effects, including type 1 diabetes mellitus 1 . We describe here a case of anti-PD-1 antibody therapy, nivolumabinduced type 1 diabetes mellitus, which developed within 9 days of treatment.…”

Case of acute‐onset type 1 diabetes induced by long‐term immunotherapy with nivolumab in a patient with mucosal melanoma

“…2 The mean duration of T1DM development is 155 days. 3 We present a case of delayed acute-onset T1DM in a patient with mucosal melanoma of the nasal cavity, treated with nivolumab.An 80-year-old woman with no history of diabetes (hemoglobin A1c [HbA1c], 5.5%), received irradiation for BRAFwild, mucosal melanoma of her nasal cavity in 2013. In August 2016, she developed stage IV melanoma with multiple metastases and was treated with nivolumab as the first-line therapy (Fig.…”

“…2 The mean duration of T1DM development is 155 days. 3 We present a case of delayed acute-onset T1DM in a patient with mucosal melanoma of the nasal cavity, treated with nivolumab.…”

“…The mean duration of T1DM development is 155 days (range, 13-504). 3 All cases of T1DM by anti-PD-1 immunotherapy are classified as acute-onset or fulminant type. 3 Further, acute-onset type T1DM is classified into autoimmune and idiopathic types.…”

“…3 All cases of T1DM by anti-PD-1 immunotherapy are classified as acute-onset or fulminant type. 3 Further, acute-onset type T1DM is classified into autoimmune and idiopathic types. Autoimmune type is diagnosed if anti-islet autoantibodies are detected, 5 which were negative in the present case.…”