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A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab

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Abstract

The case was an 80-year-old Japanese man. He was diagnosed with right renal cell carcinoma when he was 74. After laparoscopic radical nephrectomy, the patient received interferon, sorafenib, axitinib, and nivolumab therapy. The patient developed rapid progressive insulin-dependent diabetes mellitus (DM) after 46 courses of nivolumab monotherapy (772 days from the first nivolumab treatment). Glutamic acid decarboxylase antibody, islet cell cytoplasmic antibody, islet cell antigen-2 antibody, insulin antibody, and zinc transporter 8 antibody were all negative. Human leukocyte antigen (HLA) typing showed DRB1*09:01, DRB1 *13:02, DQB1*03:03, and DQB1 *06:04. Multiple daily insulin injections were started. However, controlling his blood glucose by standard multiple daily insulin injection treatments was difficult. The patient survived more than two years after the onset of immune checkpoint inhibitor-associated DM (ICI-DM). This is a valuable report of late-onset ICI-DM with a detailed patient background and clinical course over two years after the first dose of nivolumab.

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Acknowledgements

The authors thank Corina N D'Alessandro-Gabazza for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Diabetes, Metabolism, and Endocrinology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie, 514-8507, Japan

    Kota Nishihama, Yuko Okano, Chisa Inoue, Kanako Maki, Kazuhito Eguchi, Soichiro Tanaka, Atsuro Takeshita, Mei Uemura, Taro Yasuma, Toshinari Suzuki & Yutaka Yano

  2. Department of Immunology, Mie University Graduate School of Medicine, Tsu, Japan

    Esteban C. Gabazza

Authors
  1. Kota Nishihama
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  2. Yuko Okano
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Contributions

KN was responsible for clinical treatment and prepared the manuscript. YO, CI, KM, KE, ST, AT, MU, TY, and TS were responsible for clinical treatment and follow-up. ECG, and YY were responsible for interpreting the data and intellectual contribution to preparing the manuscript.

Corresponding author

Correspondence to Yutaka Yano.

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Conflict of interest

Yutaka Yano reports receiving lecture fees from Novo Nordisk and Sumitomo Pharma. Other authors declared no conflict of interest regarding this manuscript.

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Written informed consent for the publication was obtained from the patient.

Research involving human participants and/or animals

All procedures followed the Helsinki Declaration of 1964 and later versions. This article contains no studies with human or animal subjects performed by authors. The identity of the patient has been protected.

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Nishihama, K., Okano, Y., Inoue, C. et al. A case of rapidly progressive insulin-dependent diabetes mellitus without islet autoantibodies developed over two years after the first dose of nivolumab. Diabetol Int (2024). https://doi.org/10.1007/s13340-024-00703-y

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  • DOI: https://doi.org/10.1007/s13340-024-00703-y

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