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Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune checkpoint inhibitor treatment for advanced renal cell carcinoma

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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.

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Acknowledgments

The authors thank Yohei Yamanaka and Shingo Takada of the Department of Urology, Osaka Police Hospital, for their cooperation in writing this paper.

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Authors and Affiliations

  1. Department of Diabetes and Endocrinology, Osaka Police Hospital, 10-31 Kitayama-cho Tennoujiku, Osaka, 543-0035, Japan

    Hiroki Yamaguchi, Yumika Miyoshi, Yuhei Uehara, Kohei Fujii, Shimpei Nagata, Yoshinari Obata, Motohiro Kosugi, Yoji Hazama & Tetsuyuki Yasuda

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  1. Hiroki Yamaguchi
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  2. Yumika Miyoshi
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Correspondence to Tetsuyuki Yasuda.

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Conflicts of interest

Tetsuyuki Yasuda has received lecture fees from Takeda Pharmaceutical Company Limited, Novartis Pharmaceuticals Corp., and Nippon Boehringer Ingelheim Co., Ltd. The other authors declare that they have no conflicts of interest.

Human rights statement and informed consent

All procedures were approved by the appropriate institutional review board (the Ethics Committee of Osaka Police Hospital, approved April 28, 2020, approval number: 1190) and complies with the Declaration of Helsinki and its amendments. Informed consent was obtained from the patient for the publication of this case report.

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Yamaguchi, H., Miyoshi, Y., Uehara, Y. et al. Case of slowly progressive type 1 diabetes mellitus with drastically reduced insulin secretory capacity after immune checkpoint inhibitor treatment for advanced renal cell carcinoma. Diabetol Int 12, 234–240 (2021). https://doi.org/10.1007/s13340-020-00459-1

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  • DOI: https://doi.org/10.1007/s13340-020-00459-1

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