Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune che
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CASE REPORT
Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune checkpoint inhibitor treatment for advanced renal cell carcinoma Hiroki Yamaguchi1 · Yumika Miyoshi1 · Yuhei Uehara1 · Kohei Fujii1 · Shimpei Nagata1 · Yoshinari Obata1 · Motohiro Kosugi1 · Yoji Hazama1 · Tetsuyuki Yasuda1 Received: 25 May 2020 / Accepted: 13 August 2020 © The Japan Diabetes Society 2020
Abstract We encountered a 55-year-old Japanese man with advanced renal cell carcinoma and slowly progressive type 1 diabetes mellitus (SPT1DM), whose insulin secretory capacity was drastically reduced for a brief period after only one cycle of immune checkpoint inhibitor (ICI) treatment. The patient had been diagnosed with type 2 diabetes at the age of 53 years and was treated using oral hypoglycemic agents. However, 2 years later, he was diagnosed with SPT1DM and autoimmune thyroiditis, based on the presence of anti-glutamic acid decarboxylase antibodies (GADA) and thyroid autoantibodies, which was accompanied by advanced renal cell carcinoma. At that time, his insulin secretory capacity was preserved (CPR 2.36 ng/ mL), and good glycemic control was maintained using only medical nutrition therapy (HbA1c 6.3%). He subsequently developed destructive thyroiditis approximately 2 weeks after the first cycle of ICI treatment using nivolumab (a programmed cell death-1 inhibitor) and ipilimumab (a cytotoxic T-lymphocyte-associated antigen-4 inhibitor) for advanced renal cell carcinoma. Three weeks later, his plasma glucose level markedly increased, and we detected absolute insulin deficiency and hypothyroidism. Human leukocyte antigen (HLA) analysis revealed haplotypes indicating susceptibility to type 1 diabetes mellitus (T1DM) or autoimmune thyroiditis (HLA genotype, DRB1-DQB1 *09:01–*03:03/*08:03–*06:01). He showed a good antitumor response and is currently receiving permanent insulin therapy and levothyroxine replacement with the ICI treatment. Based on this case and the available literature, patients with preexisting islet autoantibodies or SPT1DM/LADA, plus a genetic predisposition to T1DM, may have an extremely high risk of developing ICI-related T1DM for a brief period after starting ICI treatment. Keywords Slowly progressive type 1 diabetes mellitus · Islet autoantibodies · Immune checkpoint inhibitors · Nivolumab · Insulin secretion · Renal cell carcinoma
Introduction Immune checkpoint inhibitors (ICIs) modulate the immune response via cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death-1 (PD-1), or its ligand (PD-L1) [1]. Patients with several types of advanced cancers have experienced dramatically improved rates of treatment response and survival with ICIs [2], although the reduced * Tetsuyuki Yasuda [email protected] 1
Department of Diabetes and Endocrinology, Osaka Police Hospital, 10‑31 Kitayama‑cho Tennoujiku, Osaka 543‑0035, Japan
immunological tolerance to self-antigens is associated with immune-related adverse events (irAEs) [3]. Endocrine
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