A Case of Acute-onset Type 1 Diabetes following Nivolumab/Ipilimumab Combination Therapy

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  • Oryoji Yasuko
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Department of Diabetes Mellitus, Fukuoka City Hospital
  • Matsuda Yayoi
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
  • Abe Junki
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Department of Metabolic Diseases and Diabetes Mellitus, National Hospital Organization, Kokura Medical Center
  • Hino Yumika
    Department of Internal Medicine, Kotake Town Hospital
  • Nagao Toshihiko
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University Department of Metabolic Diseases and Diabetes Mellitus, Japan Community Health care Organization, Kyushu Hospital
  • Yamasita Saori
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
  • Nakao Hiroshi
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
  • Sakamoto Ryuichi
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University
  • Ohnaka Keizo
    Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University
  • Ogawa Yoshihiro
    Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University

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Other Title
  • ニボルマブ/イピリムマブ併用療法後に急性発症1型糖尿病をきたした1例

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<p>We herein report a 67-year-old man with type 1 diabetes mellitus receiving combination immune checkpoint inhibitor (ICI) therapy. He was being treated with nivolumab and ipilimumab for lung metastasis from renal cancer. After one cycle, hyperthyroidism was detected, which evolved into manifest hypothyroidism over the next few weeks, requiring levothyroxine substitution therapy. Eight weeks after initiating ICI therapy, he presented at the emergency department with thirst, weight loss, and generalized weakness. Hyperglycemia (1,234 mg/dL), anion gap metabolic acidosis (pH 7.112), and ketonemia (β-hydroxybutyrate 1,590 μmol/L) were observed. The glycated hemoglobin level was 9.1 %. Islet-related autoantibodies were all negative. The glucagon tolerance test revealed attenuated secretion of insulin. Human leukocyte antigen was heterozygous for the DRB1*0405-DQB1*0401 haplotype. We compared these findings with those of four cases of type 1 diabetes related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy at our institution. All patients showed the DRB1*0405 or DRB1*0901 HLA haplotype, which has been shown to be associated with type 1 diabetes in Japan.</p>

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