Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer

Nobumasa Ohara; Michi Kobayashi; Yohei Ikeda; Takahiro Hoshi; Shinichi Morita; Tsutomu Kanefuji; Kazuyoshi Yagi; Takeshi Suda; Toshinori Takada; Go Hasegawa; Yo Sato; Kenichiro Hirano; Shin-ichi Kosugi

doi:10.2169/internalmedicine.3208-19

CASE REPORTS

Non-insulin-dependent Diabetes Mellitus Induced by Immune Checkpoint Inhibitor Therapy in an Insulinoma-associated Antigen-2 Autoantibody-positive Patient with Advanced Gastric Cancer

Nobumasa Ohara, Michi Kobayashi, Yohei Ikeda, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Kazuyoshi Yagi, Takeshi Suda, Toshinori Takada, Go Hasegawa, Yo Sato, Kenichiro Hirano, Shin-ichi Kosugi

Author information

Nobumasa Ohara
Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Michi Kobayashi
Department of Endocrinology and Metabolism, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Department of Diabetes, Endocrinology and Metabolism, Center Hospital of the National Center for Global Health and Medicine, Japan
Yohei Ikeda
Department of Radiology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Takahiro Hoshi
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Shinichi Morita
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Tsutomu Kanefuji
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Kazuyoshi Yagi
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Takeshi Suda
Department of Gastroenterology and Hepatology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Toshinori Takada
Department of Respiratory Medicine, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Go Hasegawa
Department of Pathology, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Yo Sato
Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Kenichiro Hirano
Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan
Shin-ichi Kosugi
Department of Digestive and General Surgery, Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital, Japan

Keywords: diabetes mellitus, insulinoma-associated antigen-2 autoantibody, nivolumab, C-peptide, thyroid peroxidase autoantibody, gastric cancer

JOURNAL OPEN ACCESS

2020 Volume 59 Issue 4 Pages 551-556

DOI https://doi.org/10.2169/internalmedicine.3208-19

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Abstract

A 70-year-old man with insulinoma-associated antigen-2 autoantibodies developed diabetes mellitus (DM) without ketoacidosis after starting nivolumab to treat advanced gastric cancer. He subsequently exhibited preserved insulin-secretion capacity for over one year. Immune checkpoint inhibitors (ICIs) infrequently cause type 1 DM associated with the rapid loss of insulin secretion and ketoacidosis as an immune-related adverse event. ICIs may also cause non-insulin-dependent DM by inducing insulin resistance if there is islet autoantibody-related latent beta-cell dysfunction. The present case highlights the importance of testing blood glucose levels regularly to diagnose DM in patients treated with ICIs, even if they do not have diabetic ketoacidosis.

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